quinta-feira, 31 de maio de 2007
Avandia: resposta da Glaxo Smith Kline
Estou em Belo Horizonte, em reunião do Estudo Longitudinal de Saúde do Adulto, com restrição de acesso. Leiam a resposta da Glaxo sobre o Avandia em carta ao The Lancet.
quarta-feira, 30 de maio de 2007
Mais um perigo nos ares: Tuberculose
Talvez a informação abaixo do The New York Times seja de utilidade para quem viajou nos vôos abaixo. Mas, não é a primeira vez que tais fatos são identificados. Há seis meses, o Hospital Universitário internou com meningite meningocócica paciente com dupla nacionalidade brasileira e italiana que morava na Itália com sintomas já no vôo para São Paulo. Ele permaneceu 12 horas infectado em um avião de carreira. As autoridades sanitárias italianas foram avisadas à época, mas não houve contágio descrito.
TB Patient Is Isolated After Taking Two Flights By LAWRENCE K. ALTMAN Published: May 30, 2007
Federal and international officials are tracking down passengers and crew members on two trans-Atlantic flights earlier this month who may have been exposed to a man infected with an exceptionally dangerous form of tuberculosis.The male passenger flew to Paris from his home in Atlanta on May 12 on Air France 385 and arrived in Paris on May 13. He returned to the United States on May 24 after taking Czech Air 104 to Montreal from Prague. The man drove into the United States that day and entered a hospital in New York City on May 25.The man is now in an Atlanta hospital under federally enforced isolation after he was flown there from New York City on Monday in a plane owned by the Centers for Disease Control and Prevention in Atlanta.Dr. Martin S. Cetron , an agency official, said he reached the man on his cellphone while he was in Italy to inform him that tests performed before he left for Europe showed that he had a form of tuberculosis that was extremely resistant to standard antibiotics. Dr. Cetron said that he advised the man not to take commercial flights home from Europe and that a United States Embassy would provide assistance, including examination by a tuberculosis expert.While the agency began to explore ways to bring the man home, he flew to Montreal and drove into the United States. Then, after agency officials made contact with him, he followed their instructions to drive safely into New York without risk to the public.The New York City health department said the man spent 72 hours in a hospital in isolation and did not interact with anyone other than trained medical workers.The disease control agency said that because it was the first airline contact investigation for extremely drug resistant tuberculosis, it was not sure that current recommendations were adequate to determine the possible range and risk of transmission on infection.Dr. Julie L. Gerberding, director of the C.D.C., said her agency was advising passengers on the commercial flights to be tested for tuberculosis even though they are believed to have a low risk of infection.That appraisal was based on tests showing that the number of tuberculosis bacteria in the man’s sputum were too low to be detected but still enough to infect others. Dr. Gerberding said her agency was erring on the side of caution because the form of tuberculosis, known as XDR TB, was often fatal and a growing public health threat in many countries.The advisory applies only to the crew members on the man’s flight and to his fellow passengers, particularly those who were seated next to him and in the two rows behind him and the two rows in front of him.“We’re not concerned about a generic threat to travelers,” Dr. Gerberding said.Drug-susceptible, or regular, TB and XDR TB are thought to be spread the same way. The TB bacteria become aerosols when a person coughs, sneezes, speaks or sings. The bacteria can float in the air for several hours, depending on the environment. People who breathe air containing these bacteria can become infected.The risk of acquiring any type of TB appears to depend on several factors, such as the extent of disease in the person who is the source of the bacteria, the duration of exposure and ventilation.People who become infected have usually been exposed for several hours or days in poorly ventilated or crowded environments. An important way to prevent the spread and transmission is by limiting an infectious person’s contact with other people. People who have a confirmed diagnosis of TB or XDR TB are placed on treatment and kept isolated until they are no longer infectious. Contact passengers will be advised to undergo a medical evaluation and testing and then have follow-up tests 8 to 10 weeks later.Dr. Gerberding said doctors had not determined the source of the man’s infection. Molecular fingerprints used to distinguish among bacterial strains so far do not match that of any other known case, she said. People who think they may have been exposed to TB or XDR TB can call (800) CDC-INFO for more information.
Federal and international officials are tracking down passengers and crew members on two trans-Atlantic flights earlier this month who may have been exposed to a man infected with an exceptionally dangerous form of tuberculosis.The male passenger flew to Paris from his home in Atlanta on May 12 on Air France 385 and arrived in Paris on May 13. He returned to the United States on May 24 after taking Czech Air 104 to Montreal from Prague. The man drove into the United States that day and entered a hospital in New York City on May 25.The man is now in an Atlanta hospital under federally enforced isolation after he was flown there from New York City on Monday in a plane owned by the Centers for Disease Control and Prevention in Atlanta.Dr. Martin S. Cetron , an agency official, said he reached the man on his cellphone while he was in Italy to inform him that tests performed before he left for Europe showed that he had a form of tuberculosis that was extremely resistant to standard antibiotics. Dr. Cetron said that he advised the man not to take commercial flights home from Europe and that a United States Embassy would provide assistance, including examination by a tuberculosis expert.While the agency began to explore ways to bring the man home, he flew to Montreal and drove into the United States. Then, after agency officials made contact with him, he followed their instructions to drive safely into New York without risk to the public.The New York City health department said the man spent 72 hours in a hospital in isolation and did not interact with anyone other than trained medical workers.The disease control agency said that because it was the first airline contact investigation for extremely drug resistant tuberculosis, it was not sure that current recommendations were adequate to determine the possible range and risk of transmission on infection.Dr. Julie L. Gerberding, director of the C.D.C., said her agency was advising passengers on the commercial flights to be tested for tuberculosis even though they are believed to have a low risk of infection.That appraisal was based on tests showing that the number of tuberculosis bacteria in the man’s sputum were too low to be detected but still enough to infect others. Dr. Gerberding said her agency was erring on the side of caution because the form of tuberculosis, known as XDR TB, was often fatal and a growing public health threat in many countries.The advisory applies only to the crew members on the man’s flight and to his fellow passengers, particularly those who were seated next to him and in the two rows behind him and the two rows in front of him.“We’re not concerned about a generic threat to travelers,” Dr. Gerberding said.Drug-susceptible, or regular, TB and XDR TB are thought to be spread the same way. The TB bacteria become aerosols when a person coughs, sneezes, speaks or sings. The bacteria can float in the air for several hours, depending on the environment. People who breathe air containing these bacteria can become infected.The risk of acquiring any type of TB appears to depend on several factors, such as the extent of disease in the person who is the source of the bacteria, the duration of exposure and ventilation.People who become infected have usually been exposed for several hours or days in poorly ventilated or crowded environments. An important way to prevent the spread and transmission is by limiting an infectious person’s contact with other people. People who have a confirmed diagnosis of TB or XDR TB are placed on treatment and kept isolated until they are no longer infectious. Contact passengers will be advised to undergo a medical evaluation and testing and then have follow-up tests 8 to 10 weeks later.Dr. Gerberding said doctors had not determined the source of the man’s infection. Molecular fingerprints used to distinguish among bacterial strains so far do not match that of any other known case, she said. People who think they may have been exposed to TB or XDR TB can call (800) CDC-INFO for more information.
Mudando de Avandia para Actos
The Wall Street Journal (assinante clique aqui) que médicos americanos evitam Avandia e, ao mesmo tempo prescrevem mais Actos (pioglitazone). Há uma grande chance que a maioria dos pacientes, ao invés da prescrição de um desses dois medicamentos se beneficiaria mais de outras condutas com redução radical de peso, aumento da atividade física, redução dos níveis de pressão arterial e de colesterol. Por isso, talvez não seja mudança adequada, somente conveniente a quem prescreve. Abaixo parte do texto.
U.S. Doctors Shun Glaxo MedicineIn Wake of Study
LONDON -- Doctors in the U.S. have shunned GlaxoSmithKline PLC's diabetes drug Avandia since a study was published last week linking the drug to greater heart-attack risk, according to early prescription data. Market-intelligence group Impact RX said Avandia's share of the market for newly prescribed oral antidiabetics fell to around zero from around 10% in the two days after the article was published in the New England Journal of Medicine on May 21. At the same time, the rate of patients switching from one drug to another was three times the usual level. Takeda Pharmaceutical Co.'s rival drug, Actos, saw its share of the new-prescription market increased to 22% from 10%. The U.K. company played down the data, saying, "Two days of data is not enough to reach sensible conclusions on the trend for Avandia new prescriptions."
LONDON -- Doctors in the U.S. have shunned GlaxoSmithKline PLC's diabetes drug Avandia since a study was published last week linking the drug to greater heart-attack risk, according to early prescription data. Market-intelligence group Impact RX said Avandia's share of the market for newly prescribed oral antidiabetics fell to around zero from around 10% in the two days after the article was published in the New England Journal of Medicine on May 21. At the same time, the rate of patients switching from one drug to another was three times the usual level. Takeda Pharmaceutical Co.'s rival drug, Actos, saw its share of the new-prescription market increased to 22% from 10%. The U.K. company played down the data, saying, "Two days of data is not enough to reach sensible conclusions on the trend for Avandia new prescriptions."
terça-feira, 29 de maio de 2007
Avandia: FDA strikes back The New England
Abaixo, transcrevo parte do texto acessível a assinantes de Scott Gottlieb publicado no The Wall Street Journal . Ele foi vice diretor do FDA no período 2005-07 e está criticando o The New England Journal of Medicine porque considera que houve "manipulação política". Em outras palavras, houve interesse em minar a atual política do FDA, da qual ele foi um dos praticantes. Segundo ele, as revistas são favoráveis a uma política mais restritiva de liberação de novos medicamentos. Gottlieb em outro texto com acesso livre há sete anos criticava a dissseminação da informação como sendo perigosa. Eu concordo com ele, a informação é perigosa. Depende sempre para quem. O aqui já citado (sem nome para não sujar essas páginas), tesoureiro pivo do mensalão não está só na sua conclusão: "transparência demais é burrice". Gottlieb faz alusão a vazamento da informação a um deputado democrata, mas a própria Glaxo foi informada, tanto que já tinha uma resposta pronta que foi publicada logo após a publicação. Ah, Gottlieb acusa a tendência esquerdista da atual direção da revista. Ironia, porque quando Marcia Angell - a editora anterior - foi substituída por Jeff Drazen dizia-se a boca pequena - leia-se The Boston Globe - que Drazen seria um representante da Big Pharma que neutralizaria a política de Marcia, uma feroz opositora da indústria farmacêutica. Ela é autora do excelente "The Truth About the Drug Companies" e há um ano deu uma entrevista `a Globo News muito didática.
Journalistic Malpractice
By SCOTT GOTTLIEBMay 29, 2007; Page A15
As medical information is exploding and becoming more accessible, all of us, particularly physicians, need objective sources to interpret data and present a balanced view. Unfortunately, major medical journals that should be filling this role often put more weight on pushing political agendas. Their editorial prejudice has left a troubling void for rigorous and unbiased arbiters of medical evidence who can guide sound medical practice decisions. The behavior of the New England Journal of Medicine (NEJM) is a case in point, when it rushed onto its Web site a limited and flawed analysis of safety concerns around the diabetes drug Avandia. The publication was timed to get ahead of the Food and Drug Administration's more careful evaluation of the same issues. The journal seemed bent on beating the FDA to the punch. The goal? Painting the FDA as impotent, in order to argue for legislation winding through Congress that would increase regulatory hurdles for drug approvals. The journal's motives were made bare by its own editorial on the matter.
By SCOTT GOTTLIEBMay 29, 2007; Page A15
As medical information is exploding and becoming more accessible, all of us, particularly physicians, need objective sources to interpret data and present a balanced view. Unfortunately, major medical journals that should be filling this role often put more weight on pushing political agendas. Their editorial prejudice has left a troubling void for rigorous and unbiased arbiters of medical evidence who can guide sound medical practice decisions. The behavior of the New England Journal of Medicine (NEJM) is a case in point, when it rushed onto its Web site a limited and flawed analysis of safety concerns around the diabetes drug Avandia. The publication was timed to get ahead of the Food and Drug Administration's more careful evaluation of the same issues. The journal seemed bent on beating the FDA to the punch. The goal? Painting the FDA as impotent, in order to argue for legislation winding through Congress that would increase regulatory hurdles for drug approvals. The journal's motives were made bare by its own editorial on the matter.
NEJM said it rushed to post the study on the Web because of its medical importance, but the FDA, which would need to act on any safety issues, wasn't even given a heads up about the study's publication or its findings. Rep. Henry Waxman (D., Calif.), however, seems to have known in advance that it was coming because he issued a substantive press release immediately after the study was posted online. He was even ready with the date and location of oversight hearings aimed at probing the FDA's "handling" of the drug safety issues. Mr. Waxman is trying to add new restrictions to the FDA's drug approvals. The study's primary author, Cleveland Clinic Cardiologist Steve Nissen, admitted to The Wall Street Journal that he was in touch with Congress while preparing his analysis. Three days after the study was submitted to NEJM, and before it was published, the FDA commissioner received a letter about Avandia from members of the House Energy and Commerce Committee that seemed to reference the NEJM study.
At what cost do political machinations of the medical journals come? NEJM editors have long favored more drug regulation. But medical journals have also historically played a special role in helping to define medical practice standards. Even decisions they make on how prominently to place a study, let alone how they editorialize about it, are seen as strong signals to clinicians on how doctors should weigh the evidence. So when editors pursue a political agenda, it's public health that pays a price. Degrading an institution that doctors depend on for balanced analysis and fair-minded editorial judgments isn't good for anyone. (.....)
There is a problem when some journals let antipathy for business interests and left-leaning views interfere with the medical decisions that they make, bending standards or stepping outside their mandate, using their prestige and influence in ways that distort medical facts in the aim of influencing political outcomes. Prestigious biomedical journals are important public health tools, provided they stick to their core business of weighing medical evidence and informing physicians of important practice advances. When they use shortcuts and shoddy analysis to fabricate criticism and doubt of drug regulation, they're no better than some politicians they increasingly comport with.
Dr. Gottlieb, a physician, is resident fellow at the American Enterprise Institute and was Deputy Commissioner of the FDA from 2005 to 2007.
At what cost do political machinations of the medical journals come? NEJM editors have long favored more drug regulation. But medical journals have also historically played a special role in helping to define medical practice standards. Even decisions they make on how prominently to place a study, let alone how they editorialize about it, are seen as strong signals to clinicians on how doctors should weigh the evidence. So when editors pursue a political agenda, it's public health that pays a price. Degrading an institution that doctors depend on for balanced analysis and fair-minded editorial judgments isn't good for anyone. (.....)
There is a problem when some journals let antipathy for business interests and left-leaning views interfere with the medical decisions that they make, bending standards or stepping outside their mandate, using their prestige and influence in ways that distort medical facts in the aim of influencing political outcomes. Prestigious biomedical journals are important public health tools, provided they stick to their core business of weighing medical evidence and informing physicians of important practice advances. When they use shortcuts and shoddy analysis to fabricate criticism and doubt of drug regulation, they're no better than some politicians they increasingly comport with.
Dr. Gottlieb, a physician, is resident fellow at the American Enterprise Institute and was Deputy Commissioner of the FDA from 2005 to 2007.
Avandia: rumo ao precipício?
Do sempre bem informado blogueiro do WSJ.
Avandia Dips: Pothole or Cliff?
Posted by Jacob Goldstein
New prescriptions of GlaxoSmithKline’s Avandia dipped sharply last week after the New England Journal of Medicine published a study suggesting the diabetes drug raised the risk of heart attacks, according to pharma research shop ImpactRx.
In a note to investors this morning, Deutsche Bank cited ImpactRx data showing that Avandia’s market share of newly prescribed diabetes pills fell from about 10% before the NEJM paper to roughly zero in the two days after the paper was published. The situation “is far worse than we had anticipated and suggests that there could be as much as 22% downside risk to GSK’s near term earnings,” the note said.
But the data don’t support such a far-reaching prediction, ImpactRx CEO Richard Altus argued in an interview with the Health Blog. “It’s premature to draw any conclusions from our data with respect to the future script writing of Avandia,” he said, adding that he was “shocked” at Deutsche Bank’s interpretation of his company’s figures. GlaxoSmithKline and Deutsche Bank have both been clients of ImpactRx, but Altus said he was not acting at GSK’s request.
The Health Blog couldn’t reach the London-based authors of the note Tuesday afternoon for comment.
Posted by Jacob Goldstein
New prescriptions of GlaxoSmithKline’s Avandia dipped sharply last week after the New England Journal of Medicine published a study suggesting the diabetes drug raised the risk of heart attacks, according to pharma research shop ImpactRx.
In a note to investors this morning, Deutsche Bank cited ImpactRx data showing that Avandia’s market share of newly prescribed diabetes pills fell from about 10% before the NEJM paper to roughly zero in the two days after the paper was published. The situation “is far worse than we had anticipated and suggests that there could be as much as 22% downside risk to GSK’s near term earnings,” the note said.
But the data don’t support such a far-reaching prediction, ImpactRx CEO Richard Altus argued in an interview with the Health Blog. “It’s premature to draw any conclusions from our data with respect to the future script writing of Avandia,” he said, adding that he was “shocked” at Deutsche Bank’s interpretation of his company’s figures. GlaxoSmithKline and Deutsche Bank have both been clients of ImpactRx, but Altus said he was not acting at GSK’s request.
The Health Blog couldn’t reach the London-based authors of the note Tuesday afternoon for comment.
China: condenado a morte por corrupção
O blogueiro do WSJ destacou a condenação a morte do ex-diretor do equivalente à ANVISA chinesa. Denuncio aqui a sentença de morte e gostaria de conhecer o nome das oito companhias que participaram da "mutreta".
Death Sentence for China’s Former Top Drug Regulator Posted by Jacob Goldstein
Zheng Xiaoyu, the first chief of China’s State Food and Drug Administration, was sentenced to death today for taking $850,000 in bribes from eight unnamed drug companies, WSJ.com reports.The sentence comes as China struggles with a series of domestic and international incidents arising from food and medicines — ranging from pet chow to toothpaste to antibiotics. Zheng (pictured, left) ran China’s FDA from its founding in 1998 until 2005, the New York Times reports He was detained in February along with two other top regulators. Officials are now reviewing over 170,000 licenses issued by the agency over the past decade, according to the Times. The death sentence, handed down by Beijing Municipal No. 1 Intermediate People’s Court, said that Zheng’s acts “endangered public life and health and had a very negative social impact,” according to China’s Xinhua news service
Zheng Xiaoyu, the first chief of China’s State Food and Drug Administration, was sentenced to death today for taking $850,000 in bribes from eight unnamed drug companies, WSJ.com reports.The sentence comes as China struggles with a series of domestic and international incidents arising from food and medicines — ranging from pet chow to toothpaste to antibiotics. Zheng (pictured, left) ran China’s FDA from its founding in 1998 until 2005, the New York Times reports He was detained in February along with two other top regulators. Officials are now reviewing over 170,000 licenses issued by the agency over the past decade, according to the Times. The death sentence, handed down by Beijing Municipal No. 1 Intermediate People’s Court, said that Zheng’s acts “endangered public life and health and had a very negative social impact,” according to China’s Xinhua news service
Trasylol: risco mantido de insuficiência renal
O caso “Trasylol” (aprotinina) já foi aqui discutido duas vezes. Trata-se de medicamento utilizado em cirurgia cardíaca com riscos maiores do que os descritos pela empresa inicialmente. Ela foi também acusada pelo FDA de não incluir 65 mil participante no estudo de segurança. Hoje, Circulation (clique aqui para ler o resumo) publica metanálise com resultados um pouco diferentes, à favor da segurança da aprotinina, mas revelando que doses altas se associam a risco de insuficiência renal. No entanto, o custo do medicamento não justifica seu uso comparado aos demais concorrentes
Um pouco de feijão com arroz e menos Avandia.
A Fundação Getúlio Vargas divulgou ontem (Valor Econômico) que o consumo de arroz com feijão foi de 085% do orçamento familiar, mas que o gasto com cigarros representou 1,25%. A questão do tabagismo além do dano à saúde para os mais pobres é um problema econômico sério. Agora que a Big Pharma também está com bons produtos na área, é o caso de avançarmos ainda mais nas políticas corporativas e locais de controle do tabagismo. Para os adeptos da "falência da saúde pública", lembrem o que era uma viagem aérea há dez anos.
Recomendo o programa do Hospital Universitário da USP com exemplo de atividade de qualidade nessa área.
Desfecho: a palavra-chave no caso Avandia e outros.
Hoje, o The New York Times (texto completo para registrados) aborda a questão "Avandia" verificando os critérios utilizados para concluir se um medicamento é útil ou não. Essa é uma das aulas básicas nos curso de epidemiologia:"ensaio clínico". Há tratamentos que nunca foram e nunca foram testados, como por exemplo o uso de penicilina para tratar pneumonia, porque a sua eficácia e efetividade foram tão evidentes que dispensou qualquer ensaio comparativo do antibiótico com um placebo. No entanto, quando entramos nas era das doenças crônicas com duração prolongada, a capacidade de observar se houve melhora ou não somente pela observação médica se reduziu. Surgiram então os ensaios clínicos que testam um medicamento versus placebo ou um medicamento contra outro com critérios rigorosos independente do médico. E, nesse caso há um desfecho (outcome) a ser alcançado. Aí, na definição do desfecho que surgem os problemas. Como foi abordado por Nissen no artigo mais discutido, mas não tão lido - da última semana: é um erro aprovar medicamento para diabetes somente com o desfecho "redução da glicemia". Afinal, o objetivo principal é reduzir a carga de doença cardiovascular no diabético e, não a diminuição "cosmética" da glicemia. Um exemplo com mais de 30 anos: um medicamento foi lançado por reduzia o colesterol, diminuia o número de infartos do miocárdio e , da mesma forma a mortalidade cardiovascular.Ótimo, não? Não, porque aumentou a mortalidade por outras causas, por isso não vingou. Ou seja não adianta verificar se o medicamento afetou parte do mecanismo fisiopatológico, mas sim se houve um ganho efetivo para quem dele se utiliza. Abaixo, parte do texto do NYT com outros exemplos e também o custo da extensão dos ensaios clínicos dos surrogate outcomes para os hard outcomes.
By DENISE GRADY Published: May 29, 2007
People with diabetes have too much sugar in their blood, so a drug that lowers blood sugar ought to be a good treatment, right? Maybe not. Consider the diabetes drug Avandia, or rosiglitazone, which was approved in 1999. It lowers blood sugar, and about a million people in the United States have been taking it for Type 2 diabetes, the most common form of the disease. But last week, doctors reported that Avandia might increase the risk of heart attacks. ...... Avandia was approved because it lowered blood sugar, and seemed safe in clinical trials. But the real test of whether a drug is any good is, How are the patients? Not their blood tests or X-rays or EKGs, but the people themselves, and not after just six months, but after years, especially if they have a chronic disease and will be taking medicine for the rest of their lives. Are those taking the drug more or less likely than people not taking it to have heart attacks, die or develop heart disease or other illnesses?
The problem is, it can take a long time and a lot of patients — and, therefore, a lot of money — to get a real picture of health and survival. That is especially true for something like heart disease, which develops slowly and is so common that it may be hard to detect a small increase in risk. Studies might have to go on for years instead of months, and include far more than the few thousand patients in whom drugs are typically tested before they get approved. So instead of waiting to see if people die or have heart attacks, drug companies have looked for other traits that seem to correlate with health and survival and that could stand in as a yardstick — objective measures like blood pressure, cholesterol levels, blood sugar or tests of heart function. Researchers call these measurements “surrogate endpoints,” and the F.D.A. has encouraged companies to find surrogates that could reliably predict how patients would fare. These kinds of tests are seen as a way to streamline the drug approval process. But reliable surrogates are hard to find. There are plenty of endpoints that in theory should do the job, but do not. Tumor size, for instance: there are drugs that can shrink tumors without prolonging a patient’s life. Bone density is another example. Fluoride can increase it in people whose skeletons have thinned from osteoporosis, so fluoride should prevent fractures. But it doesn’t. In fact, it makes fractures more likely, because it turns bones brittle. Heart rhythm can also be deceptive. Certain medicines can stabilize dangerous, abnormal heartbeats in people who have had heart attacks — and yet have been found to increase their odds of dying. Cholesterol levels do not always tell the whole story, either. Hormone treatment in women after menopause can raise HDL, the so-called good cholesterol, and so was expected to prevent heart disease — but does not. Similarly, researchers had high hopes for an experimental drug that raises HDL, but instead of preventing heart attacks the drug wound up increasing the risk. Part of the problem is that surrogate endpoints do not always reflect what’s happening to the whole patient. The disease being treated may be too complicated to gauge with just one tool, and the drug in question may have many more effects than the one being measured. ......
People with diabetes have too much sugar in their blood, so a drug that lowers blood sugar ought to be a good treatment, right? Maybe not. Consider the diabetes drug Avandia, or rosiglitazone, which was approved in 1999. It lowers blood sugar, and about a million people in the United States have been taking it for Type 2 diabetes, the most common form of the disease. But last week, doctors reported that Avandia might increase the risk of heart attacks. ...... Avandia was approved because it lowered blood sugar, and seemed safe in clinical trials. But the real test of whether a drug is any good is, How are the patients? Not their blood tests or X-rays or EKGs, but the people themselves, and not after just six months, but after years, especially if they have a chronic disease and will be taking medicine for the rest of their lives. Are those taking the drug more or less likely than people not taking it to have heart attacks, die or develop heart disease or other illnesses?
The problem is, it can take a long time and a lot of patients — and, therefore, a lot of money — to get a real picture of health and survival. That is especially true for something like heart disease, which develops slowly and is so common that it may be hard to detect a small increase in risk. Studies might have to go on for years instead of months, and include far more than the few thousand patients in whom drugs are typically tested before they get approved. So instead of waiting to see if people die or have heart attacks, drug companies have looked for other traits that seem to correlate with health and survival and that could stand in as a yardstick — objective measures like blood pressure, cholesterol levels, blood sugar or tests of heart function. Researchers call these measurements “surrogate endpoints,” and the F.D.A. has encouraged companies to find surrogates that could reliably predict how patients would fare. These kinds of tests are seen as a way to streamline the drug approval process. But reliable surrogates are hard to find. There are plenty of endpoints that in theory should do the job, but do not. Tumor size, for instance: there are drugs that can shrink tumors without prolonging a patient’s life. Bone density is another example. Fluoride can increase it in people whose skeletons have thinned from osteoporosis, so fluoride should prevent fractures. But it doesn’t. In fact, it makes fractures more likely, because it turns bones brittle. Heart rhythm can also be deceptive. Certain medicines can stabilize dangerous, abnormal heartbeats in people who have had heart attacks — and yet have been found to increase their odds of dying. Cholesterol levels do not always tell the whole story, either. Hormone treatment in women after menopause can raise HDL, the so-called good cholesterol, and so was expected to prevent heart disease — but does not. Similarly, researchers had high hopes for an experimental drug that raises HDL, but instead of preventing heart attacks the drug wound up increasing the risk. Part of the problem is that surrogate endpoints do not always reflect what’s happening to the whole patient. The disease being treated may be too complicated to gauge with just one tool, and the drug in question may have many more effects than the one being measured. ......
segunda-feira, 28 de maio de 2007
Avandia: editorial do NYT (25/05/07)
Começando a semana, com o tema da semana passada: Avandia. Abaixo, reproduzo o editorial do The New York Times da última sexta-feira que passou despercebido.. Ele faz a síntese desse episódio. A Glaxo e o FDA estão com a palavra para responder aos fatos do artigo publicado no The New England Journal of Medicine e das declarações confusas da empresa e da própria agência.. Vamos ver o que ocorrerá na semana que entra. Infelizmente não poderei acompanhar porque estarei fora para reunião do Estudo Longitudinal de Saúde do Adulto que ocorrerá em Belo Horizonte, quinta e sexta-feiras e, preparando participação em evento no exterior na próxima semana. Mas, novamente citando o beisebolista americano Yogi Berra (um Vicente Matheus local) It's like déjà vu all over again.
Editorial Ignoring the Warnings, Again?
The latest findings on Avandia, a top-selling diabetes drug, raise concerns both about its safety and about the way the manufacturer and the Food and Drug Administration have responded to signs of danger. It would be rash to make definitive judgments until the F.D.A. completes a detailed analysis. But the handling of this case bears disturbing resemblances to the Vioxx debacle, in which early warning signs were ignored by its manufacturer until the evidence of serious harm became inescapable and the drug was pulled from the market. Avandia was approved for sale in 1999 based on studies showing that it could lower blood glucose levels in patients suffering from Type 2 diabetes, also known as adult-onset diabetes. The assumption was that the drug could alleviate some of the most damaging effects of the disease, such as heart attacks and other cardiovascular ailments. But a paper just published in The New England Journal of Medicine suggests that Avandia may instead increase the risk of a heart attack by 43 percent and perhaps the risk of cardiovascular deaths as well. The study — an analysis of the combined results of 42 previous studies that compared people who took the drug with people who did not — is not definitive, and the absolute risk to any given patient is small. But the study points to a risk that could potentially harm thousands of patients a year. Its lead author was Steven Nissen, a cardiologist at the Cleveland Clinic, who blew the whistle on the cardiovascular risks of Vioxx, which adds to the sense of déjà vu.What’s most troubling is the possibility that early warning signs were not adequately heeded.Seven years ago a leading diabetes doctor warned the F.D.A. of “a worrisome trend in cardiovascular deaths,” two years later a safety monitoring group within the agency expressed concern over cases of heart failure in patients taking the drug. In late 2005 and again in August 2006 the drug’s manufacturer — GlaxoSmithKline — informed the F.D.A. that its own combined analysis of various studies showed a 31 percent increase in adverse cardiovascular events. But the company also cited studies that it said showed no evidence of harm, and the F.D.A. concluded the findings were too mixed to take immediate regulatory action.Now, prodded by Dr. Nissen’s article, the agency has issued a safety alert, is completing its own safety analysis and will convene a panel of experts to review the data. The best hope for a definitive answer may lie in a clinical trial that won’t finish monitoring all enrolled patients until late next year. If the verdict goes against Avandia, the F.D.A. and Glaxo will have a lot to explain. Congress will need to probe hard to determine what risks the agency and the manufacturer were aware of and what they did — or didn’t do — to mitigate them.
Editorial Ignoring the Warnings, Again?
The latest findings on Avandia, a top-selling diabetes drug, raise concerns both about its safety and about the way the manufacturer and the Food and Drug Administration have responded to signs of danger. It would be rash to make definitive judgments until the F.D.A. completes a detailed analysis. But the handling of this case bears disturbing resemblances to the Vioxx debacle, in which early warning signs were ignored by its manufacturer until the evidence of serious harm became inescapable and the drug was pulled from the market. Avandia was approved for sale in 1999 based on studies showing that it could lower blood glucose levels in patients suffering from Type 2 diabetes, also known as adult-onset diabetes. The assumption was that the drug could alleviate some of the most damaging effects of the disease, such as heart attacks and other cardiovascular ailments. But a paper just published in The New England Journal of Medicine suggests that Avandia may instead increase the risk of a heart attack by 43 percent and perhaps the risk of cardiovascular deaths as well. The study — an analysis of the combined results of 42 previous studies that compared people who took the drug with people who did not — is not definitive, and the absolute risk to any given patient is small. But the study points to a risk that could potentially harm thousands of patients a year. Its lead author was Steven Nissen, a cardiologist at the Cleveland Clinic, who blew the whistle on the cardiovascular risks of Vioxx, which adds to the sense of déjà vu.What’s most troubling is the possibility that early warning signs were not adequately heeded.Seven years ago a leading diabetes doctor warned the F.D.A. of “a worrisome trend in cardiovascular deaths,” two years later a safety monitoring group within the agency expressed concern over cases of heart failure in patients taking the drug. In late 2005 and again in August 2006 the drug’s manufacturer — GlaxoSmithKline — informed the F.D.A. that its own combined analysis of various studies showed a 31 percent increase in adverse cardiovascular events. But the company also cited studies that it said showed no evidence of harm, and the F.D.A. concluded the findings were too mixed to take immediate regulatory action.Now, prodded by Dr. Nissen’s article, the agency has issued a safety alert, is completing its own safety analysis and will convene a panel of experts to review the data. The best hope for a definitive answer may lie in a clinical trial that won’t finish monitoring all enrolled patients until late next year. If the verdict goes against Avandia, the F.D.A. and Glaxo will have a lot to explain. Congress will need to probe hard to determine what risks the agency and the manufacturer were aware of and what they did — or didn’t do — to mitigate them.
domingo, 27 de maio de 2007
A atualidade de Yogi Berra
" When you come to a fork in the road....Take it "
expressão de Yogi Berra, filósofo popular americano de décadas atrás, mas com atualidade cruel nos dias de hoje. Mais, visite o site http://www.yogiberra.com
Avandia: a prova da revolução da Internet
Não poderia deixar o domingo sem falar do caso "Avandia". Esperei para as revistas semanais para ler os comentários dos especialistas. Nada que fugisse do bom senso. Bom, o ZecaPagodinho quesito diabetes, está sem vencedor por falta de candidatos aptos. Mas, nos EUA, "the Irish eyes of envy", não pouparam Steven Nissen, o autor do artigo. Os comentários nos blogues por pesquisadores e médicos americanos mostram o quanto Shakespeare é eterno...... Mas, gostaria de discutir a internet.
Não há como negar como a internet - criada pelo "imperialismo ianque" ou "neoliberalismo" , mas proibida no "socialismo real" - é uma revolução. Imaginem, o tema tratado da forma tradicional.
O "New England" publicaria o texto na forma impressa. Haveria repercussão na imprensa americana e, a maioria do mundo receberia somente os despachos da Reuters e AP. Enquanto isso, a empresa colocaria toda a "força de venda" para desqualificar o autor, o método e a qualidade do artigo, o qual ninguém ainda tinha tido acesso ao texto integral. Isso ocorreu no passado com o Adalat e de certa forma com o Vioxx. Agora, a coisa foi diferente: o New England publicou no site, permitiu que o mundo todo lesse e concluísse. Enquanto isso, a versões da da empresa, FDA, EMEAS, sociedades de especialistas circularam igualmente. E, permitiram que os blogueiros pudessem opinar à vontade, questionando os dados e, principalmente o comportamento dos poderosos. Não coincidentemente esse blogue bateu o recorde de acesso.
Dedico esse post ao professor Eduardo Chaves da UNICAMP que há mais de dez anos afirmava que a internet significaria tanto para a humanidade quanto representou a criação da imprensa. Exemplificava ele (se a memória não me trai): "não haveria Lutero, sem Gutemberg. Sem a possibilidade de imprimir a Bíblia,não seria possível a Reforma Protestante e, consequentemente tudo aquilo que ela influenciou". Algúem, consegue imaginar as revoluções americana, francesa e russa sem a palavra escrita?
"Unimed Paulistana vira caso de polícia": uma pena
O Estadão divulga com essa manchete problemas na Unimed Paulistana. É uma pena, mas trata-se de problemas que os cooperativados precisam resolver comparecendo às assembléias deliberativas e exigindo balancetes periódicos compreensíveis. Nunca fui cooperativado, mas considero o sistema Unimed (a Unimed Paulistana é independente das demais) ser um dos grandes pilares da asssistência médica no Brasil, principalmente no interior de São Paulo e, cidades como Vitória, ES (27% da população). Espero que os problemas da Unimed da capital sejam solucionados pelos seus cooperativados. A atuação da UNIMED é fundamental para parcela considerável da cidade de São Paulo onde há mais de um milhão de asssociados
A importância econômica do setor saúde.
O Ministro da Saúde ocupa a página 3 da Folha de S.Paulo para descrever vários aspectos do setor saúde. Ele parte para o ataque contra a visão estúpida das equipes econômicas - desse governo e passados e, de todas as esferas de governo - que somente lamentam os gastos do setor saúde, embora seus membros adorem uma mordomia nos hospitais públicos para si, familiares e amigos. Destaca o desaparelhamento da indústria, já citado nesse blogue como sendo o grande problema da atualidade no setor saúde. Acrescentaria a esse texto, a não desprezível atividade econômica do "turismo da saúde" com a ocupação de hotéis, por familiares, por exemplo que se dirigem a centros de excelência. Abaixo, parte do texto de José Gomes Temporão e Carlos Grabois Gadelha.
O entendimento dessas atividades como ônus ao orçamento público é cego. O segmento contribui para cidadania, investimentos, inovações, renda, emprego e receitas ao Estado. A cadeia produtiva representa entre 7% e 8% do PIB (R$ 160 bilhões). Emprega, com trabalho formal, 10% da população e é a área em que os investimentos públicos com pesquisa e desenvolvimento são os mais expressivos no país. O mercado farmacêutico brasileiro movimenta R$ 22 bilhões, equipamentos médico-hospitalares, R$ 6 bilhões, e vacinas, reagentes e hemoderivados, R$ 3 bilhões. São indústrias que geram 300 mil empregos diretos. Na prestação de serviços, 77 mil estabelecimentos de saúde empregam 1,6 milhão de pessoas (mais da metade com nível superior e alta qualificação). Por ano, o SUS realiza 2,8 mil transplantes renais, 215 mil cirurgias cardíacas e 9 milhões de procedimentos de rádio e quimioterapia, refletindo capacitação do sistema que se destaca entre países com grau semelhante de desenvolvimento. Há, porém, enorme fragilidade econômica e tecnológica. As indústrias perderam competitividade internacional ao longo da década de 90. O déficit acumulado cresceu de US$ 700 milhões ao ano, no final dos anos 80, para US$ 4 bilhões, sendo 60% concentrados na área farmacêutica. Um país desenvolvido requer base produtiva forte para atender a inclusão social e atenuar as desigualdades. O Brasil apresenta grande possibilidade de superação dessa vulnerabilidade. Nossa base produtiva, ciência, recursos humanos qualificados e sistema de saúde universal conferem ao Estado elevado poder de compra de bens industriais, com financiamento de longo prazo pelo BNDES. Fatores singulares na realidade latino-americana. Significa que a saúde é frente de expansão e janela de oportunidades ao padrão de desenvolvimento humanizado, equânime e solidário. (restante da matéria para assinantes da Folha)
A tecnologia insuperável: a observação humana.
A Folha de S.Paulo publicou uma matéria excelente de Marcelo Coelho questionando a propalada biodiversidade amazônica e, a importância estratégica para a indústria farmacêutica. O Centro Biotecnológica da Amazônia é um fracasso. Ponto final. Os novos medicamentos virão muito mais da beira do leito, dos consultórios e pronto-socorros associados aos laboratórios de pesquisadores básicos localizados em grandes centros urbanos. A base para as novas descobertas será a tecnologia mais desenvolvida até o momento: a observação humana. Como dizia, um filósofo popular americano - equivalente ao nosso Vicente Matheus - o jogador de beisebol Yogi Berra: "you can see a lot of things watching".
Uma consulta à página na internet do Centro de Biotecnologia da Amazônia, em Manaus, revela que os 12 mil metros quadrados da instalação contêm espaço para 25 laboratórios, mas abrigam só nove doutores e, ao todo, menos de cem funcionários. Se a Amazônia fosse de fato o Celeiro de Genes do mundo, o Pulmão Molecular do planeta, seu Eldorado Tecnobiológico, como explicar que permaneça vazio o elefante branco no Distrito Industrial da Zona Franca de Manaus?Há muitas explicações, decerto, a começar pela carência de recursos humanos qualificados na região. No passado, em 2000, também fracassou um acordo entre a iniciativa BioAmazônia e a empresa Novartis, firmado à revelia do governo federal e por ele anulado. Havia sido moldado em acordo similar firmado uma década antes, e dado como paradigma da bioprospecção, entre a empresa Merck e o INBio, do governo da Costa Rica, pela quantia de 2,8 milhões de dólares, do qual hoje ninguém mais fala.Do acordo brasileiro se pode dizer que naufragou por impróprio e por força da saudável reação social aos seus termos e condições. Mas o que dizer dos parcos resultados colhidos pelo INBio e, provavelmente, do futuro acanhado do CBA?Com certeza, que a bioprospecção não tem rendido nem uma fração do que prometia em 1992. Naquele ano se negociou no Rio de Janeiro a versão final da Convenção-Quadro das Nações Unidas sobre Diversidade Biológica, consagrando o generoso princípio da repartição de benefícios pelo uso de saberes tradicionais. O objetivo, aqui, é precisamente este: questionar a idéia feita de que a Amazônia represente uma espécie de Paraíso Genético, imagem fadada a se desfazer, assim como se desfizeram as do Pulmão Verde do mundo e do Celeiro de Alimentos. (assinante da Folha clique aqui).
sábado, 26 de maio de 2007
Avandia: a cavalaria não chegará em tempo RECORD
A defesa da Glaxo Smith Kline para a metanálise apresentada por Nissen (e, ao que parece pelo FDA também) viria dos resultados parciais do estudo RECORD. Porém devido à publicação do artigo de Nissen, os participantes do RECORD estão abandonando o ensaio clínico. Sinceramente, não dá para entender a preocupação da empresa, afinal, ela afirma que os resultados parciais quando adicionados aos demais mostraria exatamente o oposto ao publicado, ou seja um fator cardiovascular protetor da rosiglitazone.
Test of Drug for Diabetes in Jeopardy
By STEPHANIE SAUL Published: May 26, 2007
A large clinical study meant to test the heart safety of the diabetes treatment Avandia may be in jeopardy as a result of recent reports of the drug’s risks, according to an executive at its maker, GlaxoSmithKline.
Dr. Ronald L. Krall, the medical director for GlaxoSmithKline, said in a telephone interview yesterday that some of the 4,450 patients enrolled in the drug trial, called Record, have dropped out this week because of safety concerns about Avandia. Dr. Krall said he did not yet know how many patients have withdrawn, but said Glaxo was now worried about whether it could complete the drug trial, which has been scheduled to run through next year. The company has been counting on a successful outcome from the study to dispel widespread concerns that Avandia carries a higher risk of heart attacks than other diabetes drugs. Now, though, the independent research committees overseeing the study “are concerned about the ability of the study to continue” and are “considering what to do to prevent people from dropping out of the trial,” Dr. Krall said. The safety concerns were ignited by an analysis published Monday in The New England Journal of Medicine suggesting that Avandia, used to treat Type 2 diabetes, carries an increased risk of heart attack, estimated at 43 percent, compared with other diabetes drugs or placebos. In response to the medical journal article, the Food and Drug Administration, issued a safety alert for Avandia and advised patients who take it to consult their doctors. Avandia, which was approved by the F.D.A. in 1999, has been used by an estimated seven million people, six million of them in the United States. Yesterday, the F.D.A. said its own recent analysis of more than 40 clinical studies of Avandia seemed to confirm the findings in The New England Journal of Medicine’s study, whose lead author was the influential Cleveland Clinic heart specialist Steven E. Nissen. But an agency spokeswoman yesterday urged caution in interpreting those results. “Dr. Nissen’s meta-analysis and the F.D.A.’s meta-analysis both arrived at a similar figure of 40 percent” the F.D.A. spokeswoman, Julie Zawisa, wrote in an e-mail message. “But this alone, is not conclusive of anything. What it does mean is that we need to try to reconcile the meta-analysis finding with clinical trial data that DO NOT show this increased risk.”People with Type 2 diabetes are already at risk of heart attacks, facing a 20.2 percent chance of such an attack over seven years. One of the main reasons for controlling blood sugar in diabetic patients is to manage that risk. But if Dr. Nissen’s analysis is an accurate reflection of Avandia’s increased risk, it appears the drug would do more cardiovascular harm than good. Diabetics taking Avandia would run a 28.9 percent chance of heart attack over the same seven-year period, according to his analysis.
GlaxoSmithKline’s own meta-analysis, submitted to the F.D.A. last August, showed a slightly lower 31 percent increased risk of heart attack. A meta-analysis, which involves comparing the results of disparate clinical trials, is not considered as definitive as a uniform, controlled patient study of the sort GlaxoSmithKline has been counting on with its Record trial. Both GlaxoSmithKline and the F.D.A. have said that the meta-analyses indicating a heart risk with Avandia are contradicted by an interim look at Record, as well as data from an analysis of more than 20,000 patients enrolled in a UnitedHealthcare plan.But neither GlaxoSmithKline nor the F.D.A. has released results from that interim assessment of Record, which was conducted within the last month. The F.D.A. has received heavy criticism this week from Capitol Hill, where members of Congress have suggested that Avandia is shaping up as another Vioxx — a painkiller that became a bestseller, despite periodic questions about its safety, before being taken off the market in 2004 when its heart risks became irrefutable. The F.D.A. plans to ask an advisory panel to review the Avandia data. Such panels, if they find safety risks with a drug, can recommend that the agency require a stronger warning label or ban the drug altogether. Avandia is Glaxo’s second-largest selling drug, with more than $3 billion in sales last year worldwide. The company’s American depository receipts fell nearly $5 this week on news of safety concerns about the drug. The shares closed yesterday at $52.43. GlaxoSmithKline has urged regulators and the public not to rush to judgment based on the New England Journal of Medicine article and has said that the Record trial, which began in 2000, would be a more reliable way to estimate the drug’s cardiovascular risks. In that study, half of the 4,450 patients are being treated with Avandia in combination with another diabetes drug, while the others are being treated with two other drugs. The trial is designed to determine whether patients taking Avandia are more likely to have a range of cardiovascular problems, including heart attack and stroke
By STEPHANIE SAUL Published: May 26, 2007
A large clinical study meant to test the heart safety of the diabetes treatment Avandia may be in jeopardy as a result of recent reports of the drug’s risks, according to an executive at its maker, GlaxoSmithKline.
Dr. Ronald L. Krall, the medical director for GlaxoSmithKline, said in a telephone interview yesterday that some of the 4,450 patients enrolled in the drug trial, called Record, have dropped out this week because of safety concerns about Avandia. Dr. Krall said he did not yet know how many patients have withdrawn, but said Glaxo was now worried about whether it could complete the drug trial, which has been scheduled to run through next year. The company has been counting on a successful outcome from the study to dispel widespread concerns that Avandia carries a higher risk of heart attacks than other diabetes drugs. Now, though, the independent research committees overseeing the study “are concerned about the ability of the study to continue” and are “considering what to do to prevent people from dropping out of the trial,” Dr. Krall said. The safety concerns were ignited by an analysis published Monday in The New England Journal of Medicine suggesting that Avandia, used to treat Type 2 diabetes, carries an increased risk of heart attack, estimated at 43 percent, compared with other diabetes drugs or placebos. In response to the medical journal article, the Food and Drug Administration, issued a safety alert for Avandia and advised patients who take it to consult their doctors. Avandia, which was approved by the F.D.A. in 1999, has been used by an estimated seven million people, six million of them in the United States. Yesterday, the F.D.A. said its own recent analysis of more than 40 clinical studies of Avandia seemed to confirm the findings in The New England Journal of Medicine’s study, whose lead author was the influential Cleveland Clinic heart specialist Steven E. Nissen. But an agency spokeswoman yesterday urged caution in interpreting those results. “Dr. Nissen’s meta-analysis and the F.D.A.’s meta-analysis both arrived at a similar figure of 40 percent” the F.D.A. spokeswoman, Julie Zawisa, wrote in an e-mail message. “But this alone, is not conclusive of anything. What it does mean is that we need to try to reconcile the meta-analysis finding with clinical trial data that DO NOT show this increased risk.”People with Type 2 diabetes are already at risk of heart attacks, facing a 20.2 percent chance of such an attack over seven years. One of the main reasons for controlling blood sugar in diabetic patients is to manage that risk. But if Dr. Nissen’s analysis is an accurate reflection of Avandia’s increased risk, it appears the drug would do more cardiovascular harm than good. Diabetics taking Avandia would run a 28.9 percent chance of heart attack over the same seven-year period, according to his analysis.
GlaxoSmithKline’s own meta-analysis, submitted to the F.D.A. last August, showed a slightly lower 31 percent increased risk of heart attack. A meta-analysis, which involves comparing the results of disparate clinical trials, is not considered as definitive as a uniform, controlled patient study of the sort GlaxoSmithKline has been counting on with its Record trial. Both GlaxoSmithKline and the F.D.A. have said that the meta-analyses indicating a heart risk with Avandia are contradicted by an interim look at Record, as well as data from an analysis of more than 20,000 patients enrolled in a UnitedHealthcare plan.But neither GlaxoSmithKline nor the F.D.A. has released results from that interim assessment of Record, which was conducted within the last month. The F.D.A. has received heavy criticism this week from Capitol Hill, where members of Congress have suggested that Avandia is shaping up as another Vioxx — a painkiller that became a bestseller, despite periodic questions about its safety, before being taken off the market in 2004 when its heart risks became irrefutable. The F.D.A. plans to ask an advisory panel to review the Avandia data. Such panels, if they find safety risks with a drug, can recommend that the agency require a stronger warning label or ban the drug altogether. Avandia is Glaxo’s second-largest selling drug, with more than $3 billion in sales last year worldwide. The company’s American depository receipts fell nearly $5 this week on news of safety concerns about the drug. The shares closed yesterday at $52.43. GlaxoSmithKline has urged regulators and the public not to rush to judgment based on the New England Journal of Medicine article and has said that the Record trial, which began in 2000, would be a more reliable way to estimate the drug’s cardiovascular risks. In that study, half of the 4,450 patients are being treated with Avandia in combination with another diabetes drug, while the others are being treated with two other drugs. The trial is designed to determine whether patients taking Avandia are more likely to have a range of cardiovascular problems, including heart attack and stroke
Avandia: um erro conceitual
Há um erro importante na discussão sobre o Avandia tem passado despercebido até por epidemiologistas envolvidos na questão de segurança de medicamento. Trata-se da afirmativa de que o risco da rosiglitazone seria pequeno em provocar um infarto do miocárdio. A nota das sociedades brasileiras repete o mesmo equívoco. A consultora do FDA exemplificou que se um diabético teria 1% de possibilidade de infarto do miocárdio em um determinado período de tempo, o uso do medicamento aumentaria para 1,4%. Isso seria o aumento estimado em 43% estimado na metanálise de Nissen. Nenhum reparo ao ao exemplo e ao cálculo. A discordância é conceitual.
O diabetes de tipo 2 é ao mesmo tempo uma doença com sintomas – bem menores do que aqueles decorrentes do tipo 1 – motivados pela glicemia elevada e ao mesmo tempo, um fator de risco cardiovascular, decorrente da aceleração da aterosclerose em diabéticos. Ainda não há comprovação de que reduzir a glicemia implica em reduzir o risco cardiovascular. Por outro lado, há vários estudos mostrando que reduzir radicalmente a pressão arterial e o nível de colesterol reduz em muito o risco de novos eventos cardiovasculares em diabéticos. Diabéticos têm um risco de morte cardiovascular 3 vezes maior do que um não diabético.
Isso posto, o objetivo principal no tratamento de um diabético tipo 2 é diminuir o risco cardiovascular, secundado por reduzir a glicemia. Por isso, não deve haver possibilidade de risco nenhum de infarto do miocárdio decorrente do uso de medicamentos para reduzir a glicemia em diabéticos. Pequena, média ou alta, o risco é indesejável e, condena o medicamento em definitivo.
O diabetes de tipo 2 é ao mesmo tempo uma doença com sintomas – bem menores do que aqueles decorrentes do tipo 1 – motivados pela glicemia elevada e ao mesmo tempo, um fator de risco cardiovascular, decorrente da aceleração da aterosclerose em diabéticos. Ainda não há comprovação de que reduzir a glicemia implica em reduzir o risco cardiovascular. Por outro lado, há vários estudos mostrando que reduzir radicalmente a pressão arterial e o nível de colesterol reduz em muito o risco de novos eventos cardiovasculares em diabéticos. Diabéticos têm um risco de morte cardiovascular 3 vezes maior do que um não diabético.
Isso posto, o objetivo principal no tratamento de um diabético tipo 2 é diminuir o risco cardiovascular, secundado por reduzir a glicemia. Por isso, não deve haver possibilidade de risco nenhum de infarto do miocárdio decorrente do uso de medicamentos para reduzir a glicemia em diabéticos. Pequena, média ou alta, o risco é indesejável e, condena o medicamento em definitivo.
Para compreender esse conceito há outro exemplo vindo do tratamento da aids cujos objetivos são exatamente opostos. Os medicamentos utilizados com o objetivo de impedir a replicação viral e a progressão da doença aumentam os níveis de colesterol e, com grande chance aumentam o risco de infarto do miocárdio. Nesse caso, o risco cardiovascular é secundário a um objetivo maior, o de evitar a replicação do HIV. Em outras palavras, trocaria a morte certa pela aids, por um infarto do miocárdio, tratável na maioria dos casos.
sexta-feira, 25 de maio de 2007
Avandia: posição Sociedade Brasileira de Diabetes e da de Endocrinologia e Metabologia.
Comparem o texto abaixo - transcrito na íntegra - com o que já foi noticiado nesse blogue sobre o tema Avandia.
Rosiglitazona e Risco de Infarto do Miocárdio e Morte Cardiovascular
Diretoria SBD e SBEM - 25/05/2007 12:02 Posição conjunta da SBD e da SBEM
Diretoria SBD e SBEM - 25/05/2007 12:02 Posição conjunta da SBD e da SBEM
No dia 21 de maio corrente foi publicada uma meta-análise no The New England Journal of Medicine intitulado "Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes”. As conclusões da análise deste estudo sugerem que a Rosiglitazona, droga utilizada para o tratamento oral do Diabetes Mellitus tipo 2, aumenta o risco de Infarto do Miocárdio e morte por causa cardiovascular. Os autores, Steven Nissen e Kathy Wolski, cometam a dificuldade destas conclusões pois não tiveram acesso aos dados completos dos pacientes. O editorial da NEJM, publicado no mesmo dia, segue nesta mesma direção. A American Diabetes Association, American College of Cardiology e American Heart Association se posicionaram em conjunto e comentam que embora o risco pareça baixo é necessário considerar cautelosamente estes dados. A FDA (Food and Drug Administration), em seu posicionamento, liberado recentemente em nota, se preocupa com os dados, mas que os resultados publicados e não-publicados em estudos de longo prazo questionam estes achados. A FDA comenta, ainda, que os dados carecem de significado clínico e que, considerando o risco de mudança de medicação para pacientes diabéticos, afirma que a agência não está solicitando ao fabricante (GlaxoSmithKline) que estabeleça qualquer ação neste momento. O estudo RECORD, desenhado especificamente para analisar os desfechos cardiovasculares, trará, após sua análise completa, dados definitivos acerca do tema. A SBD e a SBEM (Sociedade Brasileira de Endocrinologia e Metabologia) recomendam aos seus associados que discutam com seus pacientes os resultados e eventuais mudanças de conduta. Reafirmam que para o tratamento do diabetes é necessária a participação efetiva do médico e do paciente na busca do controle estrito da glicemia e dos outros fatores de risco cardiovasculares associados.
* Os Drs. Marcos Tambascia e Ruy Lyra são os presidentes, respectivamente, da Sociedade Brasileira de Diabetes e Sociedade Brasileira de Endocrinologia e Metabologia
FDA também "acha" que Avandia aumenta o risco cardiovascular.
Voltando ao tema "Avandia". Despacho dessa tarde (25/05) da Reuters é reproduzido abaixo na íntegra para revelar a absoluta confusão reinante no órgão regulador americano. Para quem acha há despreparados e incompetentes somente abaixo do Equador, ao menos um consolo. Entidades científicas estão pedindo avaliação por pares sem conflito de interesse com o tema.
FDA review also shows Glaxo diabetes drug riskWASHINGTON (Reuters) - A U.S. Food and Drug Administration preliminary analysis found a level of heart-attack risk with GlaxoSmithKline Plc's diabetes drug Avandia similar to what was reported in a study earlier this week, the agency confirmed on Friday.
FDA spokeswoman Julie Zawisza stressed that other data conflicted with that finding, and officials still were weighing whether to take any action.
A Cleveland Clinic analysis released Monday said the drug increased the chances of having a heart attack by 43 percent. Speaking on the Senate floor late on Thursday, Republican Sen. Charles Grassley of Iowa said preliminary findings from an FDA analysis of Glaxo's clinical trials found a 40 percent increased risk, while the company puts the figure at about 30 percent. "Those numbers seem like a high enough threshold to me for the FDA to warn the American people of the possibility of a problem," Grassley said. The FDA's Zawisza confirmed that the agency's evaluation of Glaxo's clinical trials found a higher risk of about 40 percent. But she said "this alone is not conclusive" and officials are trying to reconcile that with clinical trial data that did not show an elevated risk. "We don't have the scientific data upon which to make any conclusions or decisions yet," she said via e-mail.
If a 40 percent risk were confirmed, it would mean that a person with diabetes who does not take the drug has about a 1 percent risk of having a heart attack or other, similar problem, while someone who takes the drug would have a 1.4 percent risk, Zawisza said.Grassley also said some FDA scientists recommended months ago that Avandia carry the strongest possible warning, a "black-box," about heart-attack risk. Zawisza said she could not comment on "ongoing regulatory matters" such as whether staff had recommended a black box. Grassley also said it had been reported to him that the incidence of heart attacks with Avandia could be as many as 60,000 to 100,000 from 1999 to 2006. He did not cite the source of the numbers, and experts say it is difficult to make such estimates across a broad population. The FDA's Zawisza said a relationship between Avandia and that number of events had not been established. "We don't have data to support such a conclusion," she said. GlaxoSmithKline spokeswoman Mary Anne Rhyne said Grassley's use of the estimate was "irresponsible." "They are extrapolations of extrapolations, and do not reflect reality. If these numbers were true, we would have seen them clearly" in long-term studies and databases of real-world use, she said. Glaxo has said Avandia's cardiovascular safety is similar to other oral diabetic drugs, and the benefits of treatment outweigh the risks. The FDA is continuing to review data on Avandia and plans to ask an advisory panel of outside experts for input. The Union of Concerned Scientists and several consumer groups wrote the FDA on Friday urging officials to chose advisers with no financial ties to Glaxo for the past 36 months. "By staffing the Avandia advisory committee with scientists from diverse specialties who are non-conflicted, you will send a message that the FDA cares about avoiding conflicts of interest and evaluating drugs on the basis of unbiased scientific findings," the letter said.
FDA spokeswoman Julie Zawisza stressed that other data conflicted with that finding, and officials still were weighing whether to take any action.
A Cleveland Clinic analysis released Monday said the drug increased the chances of having a heart attack by 43 percent. Speaking on the Senate floor late on Thursday, Republican Sen. Charles Grassley of Iowa said preliminary findings from an FDA analysis of Glaxo's clinical trials found a 40 percent increased risk, while the company puts the figure at about 30 percent. "Those numbers seem like a high enough threshold to me for the FDA to warn the American people of the possibility of a problem," Grassley said. The FDA's Zawisza confirmed that the agency's evaluation of Glaxo's clinical trials found a higher risk of about 40 percent. But she said "this alone is not conclusive" and officials are trying to reconcile that with clinical trial data that did not show an elevated risk. "We don't have the scientific data upon which to make any conclusions or decisions yet," she said via e-mail.
If a 40 percent risk were confirmed, it would mean that a person with diabetes who does not take the drug has about a 1 percent risk of having a heart attack or other, similar problem, while someone who takes the drug would have a 1.4 percent risk, Zawisza said.Grassley also said some FDA scientists recommended months ago that Avandia carry the strongest possible warning, a "black-box," about heart-attack risk. Zawisza said she could not comment on "ongoing regulatory matters" such as whether staff had recommended a black box. Grassley also said it had been reported to him that the incidence of heart attacks with Avandia could be as many as 60,000 to 100,000 from 1999 to 2006. He did not cite the source of the numbers, and experts say it is difficult to make such estimates across a broad population. The FDA's Zawisza said a relationship between Avandia and that number of events had not been established. "We don't have data to support such a conclusion," she said. GlaxoSmithKline spokeswoman Mary Anne Rhyne said Grassley's use of the estimate was "irresponsible." "They are extrapolations of extrapolations, and do not reflect reality. If these numbers were true, we would have seen them clearly" in long-term studies and databases of real-world use, she said. Glaxo has said Avandia's cardiovascular safety is similar to other oral diabetic drugs, and the benefits of treatment outweigh the risks. The FDA is continuing to review data on Avandia and plans to ask an advisory panel of outside experts for input. The Union of Concerned Scientists and several consumer groups wrote the FDA on Friday urging officials to chose advisers with no financial ties to Glaxo for the past 36 months. "By staffing the Avandia advisory committee with scientists from diverse specialties who are non-conflicted, you will send a message that the FDA cares about avoiding conflicts of interest and evaluating drugs on the basis of unbiased scientific findings," the letter said.
Política de saúde (aids ) e política industrial (medicamentos)
Uma pausa no caso Avandia. Agora, voltando ao caso efavirenz que motivou uma reportagem de Valor Econômico (25/05/07) que conseguiu ir no âmago da questão: a contradição do progama da aids. Excelente na assistência, deficiente na sustentação econômica. O Estado brasileiro está correto em desenvolver sua política de saúde pública com autonomia para reduzir dano a sua população. Fez isso de forma no caso da aids. Por outro lado, o Estado brasileiro foi incorreto ao não desenvolver a política industrial na área de medicamentos. Com isso, o "Estado brasileiro que está correto" foi penalizado pelo "Estado brasileiro que foi incorreto". Aí entram, os pescadores de águas turvas com soluções para hoje que foram as causas do erro do passado. Qual erro? Considerar três nuncas: (1) nunca poderíamos competir com a Big Pharma. (2) nunca desenvolveríamos um programa de genéricos. (3) nunca teríamos um programa de saúde pública competente. Essa inapetência pelo poder global (e, claro conflito imenso de interesse com a Big Pharma) fez com a Índia passasse na nossa frente e, conseguisse dar muita dor de cabeça à Big Pharma. Por outro lado, a política indiana para aids é pífia.
A solução agora, não é comprar remédios de indianos, não é xingar a indústria farmacêutica multinacional (nem adulá-la) mas sim desenvolver a rede de incorporação de tecnologia na área de medicamentos, oferecendo muitas vantagens para entrada no Brasil do capital da........Big Pharma acoplado a incentivos a indústria local desde que tenha perspectiva do mercado mundial. Insisto muito, que o Brasil pode ser a plataforma da Big Pharma na área não só de genéricos como de química fina.
Avandia: the Empire strikes back
The Wall Street Journal (ver parte do texto abaixo) mostra o contra-ataque da Glaxo Smith Kline e a situação aflitiva dos propagantistas farmacêuticos. O interessante não é bem o risco causado aos pacientes, mas a queda das ações da empresa. Em negrito, as mudanças da bula que na Europa já indicava risco de infarto do miocárdio.
Glaxo Courts Doctor Support of Avandia
Similar Consumer Ads Aren't Yet Planned But Won't Be Ruled Out
By JEANNE WHALEN and ANNA MATHEWS May 25, 2007 GlaxoSmithKline PLC, under pressure to protect its diabetes drug Avandia, is reaching out to physicians to defend the drug's safety but isn't currently planning a similar ad campaign for consumers.In meetings with doctors, Glaxo sales representatives are focusing on data from a large clinical trial called A Diabetes Outcome Progression Trial, or ADOPT. "We are reassuring physicians about the safety data we have, particularly looking at ADOPT," said Alice Hunt, a Glaxo spokeswoman. (…..)
Dr. Nissen's analysis led to a sharp drop in Glaxo's stock price, and some analysts have predicted Avandia sales could be cut in half because of physician and consumer concerns. The Glaxo spokeswoman said the company isn't planning consumer ads defending Avandia but won't rule them out, either. "At the moment, there is an information vacuum, and GSK may need to step into the void," she said. (…….)
When Avandia was approved, its label held a mild precaution noting that in animal studies, there had been signs of plasma volume expansion and heart hypertrophy, signals of a heart-failure risk. It also noted that while LDL, or "bad cholesterol," went up in Avandia patients, HDL, or "good cholesterol," ended up rising, as well. Later, the drug's label got a new warning that Avandia, like similar treatments, might exacerbate or lead to heart failure. The warning also noted that when taken with insulin, such drugs may "increase the risk of other cardiovascular adverse events." Last year, the Avandia label warning got beefed up a bit, saying patients with heart failure who took Avandia had a higher risk of cardiovascular events. The Glaxo analysis showing potential heart-attack risk hasn't been placed in the U.S. label, although it is mentioned in the European label. On Internet sites popular with drug-industry sales representatives, people claiming to work for Glaxo have been posting hundreds of messages this week bemoaning the difficult position Dr. Nissen's study has put them in.
Glaxo Courts Doctor Support of Avandia
Similar Consumer Ads Aren't Yet Planned But Won't Be Ruled Out
By JEANNE WHALEN and ANNA MATHEWS May 25, 2007 GlaxoSmithKline PLC, under pressure to protect its diabetes drug Avandia, is reaching out to physicians to defend the drug's safety but isn't currently planning a similar ad campaign for consumers.In meetings with doctors, Glaxo sales representatives are focusing on data from a large clinical trial called A Diabetes Outcome Progression Trial, or ADOPT. "We are reassuring physicians about the safety data we have, particularly looking at ADOPT," said Alice Hunt, a Glaxo spokeswoman. (…..)
Dr. Nissen's analysis led to a sharp drop in Glaxo's stock price, and some analysts have predicted Avandia sales could be cut in half because of physician and consumer concerns. The Glaxo spokeswoman said the company isn't planning consumer ads defending Avandia but won't rule them out, either. "At the moment, there is an information vacuum, and GSK may need to step into the void," she said. (…….)
When Avandia was approved, its label held a mild precaution noting that in animal studies, there had been signs of plasma volume expansion and heart hypertrophy, signals of a heart-failure risk. It also noted that while LDL, or "bad cholesterol," went up in Avandia patients, HDL, or "good cholesterol," ended up rising, as well. Later, the drug's label got a new warning that Avandia, like similar treatments, might exacerbate or lead to heart failure. The warning also noted that when taken with insulin, such drugs may "increase the risk of other cardiovascular adverse events." Last year, the Avandia label warning got beefed up a bit, saying patients with heart failure who took Avandia had a higher risk of cardiovascular events. The Glaxo analysis showing potential heart-attack risk hasn't been placed in the U.S. label, although it is mentioned in the European label. On Internet sites popular with drug-industry sales representatives, people claiming to work for Glaxo have been posting hundreds of messages this week bemoaning the difficult position Dr. Nissen's study has put them in.
quinta-feira, 24 de maio de 2007
Avandia: publish or publish
O lema da academia americana: "publish or perish", está sendo agora focado para a imprensa médica. Questiona-se se o The New England Journal of Medicine deveria ou não publicar o artigo sobre o rosiglitasone. Eu não tenho dúvida do acerto em publicar. Agora, estou observando a reação ao estudo. Estou no aguardo das revistas semanais para ver quem ficará com o " ZecaPagodinho quesito diabetes" Ou seja, defender quem o paga, com pouco ou nenhum conteúdo, somente desqualificando o autor do artido ou projeto que contraria o seu patrocinador, tal como o cantor fez com o Ministro da Saúde.
Porém, ninguem chegará perto de Steven Haffner, de San Antonio, Texas. Ele se considera o dono da epidemiologia do diabetes e, adora o sensacionalismo quando a seu favor. Ele transformou o diabetes no paraíso da indústria, por forçar cada vez mais definição de diabetes, que um dia atingirá toda da população. Abaixo, a opinião de diabetólogos americanos, publicado no Heartwire, um noticiário do Medscape. Vejam a declaração de Haffner e, concluam. Destaquei também parte da declaração de David Natham sobre o papel da Glaxo Smith Kline nessa questão.
Dr Steven Haffner (University of Texas Health Science Center, San Antonio), who was involved in the ADOPT study of rosiglitazone, said the paper needed to be published, but it should have undergone a more extensive review, and there should have been a different editorial with more emphasis on the flaws of the study. “The NEJM was irresponsible to go to [Drs Bruce] Psaty and [Curt] Furberg for the editorial--they were always going to emphasize concerns about drug safety; that’s what they do," he commented. “But I’m not surprised this paper was published like this. The three major medical journals are becoming more like British tabloid newspapers--all they lack is a bare-chested woman on page 3," he jibed.
Dr Brian Strom (University of Pennsylvania, Philadelphia) agrees. “Drugs are given because they have benefits. Where there’s a scare, people stop taking them. So you can do more harm than good if the scare is not based on correct information. I do believe this meta-analysis should have been published, but a less sensational editorial would have been better," he told heartwire.
Dr Robert Califf (Duke University, Durham, NC) made the point that news reporting should follow scientific discussion on drug-safety issues, not precede it. “It would be better if we had a system of postmarketing signal detection in which signals were vetted scientifically rather than splashed over TV and newspapers. I can't help but wonder if the NEJM is functioning more like the mainstream press than a scientific journal at this point, since many potential peer reviewers seem to feel that Dr Nissen's analyses are missing key elements that could have been added."
Dr Darren McGuire (University of Texas Southwestern, Dallas) commented to heartwire: “All the sensationalism surrounding this observation has created unnecessary chaos and confusion at the patient level."
Dr Steven Haffner (University of Texas Health Science Center, San Antonio), who was involved in the ADOPT study of rosiglitazone, said the paper needed to be published, but it should have undergone a more extensive review, and there should have been a different editorial with more emphasis on the flaws of the study. “The NEJM was irresponsible to go to [Drs Bruce] Psaty and [Curt] Furberg for the editorial--they were always going to emphasize concerns about drug safety; that’s what they do," he commented. “But I’m not surprised this paper was published like this. The three major medical journals are becoming more like British tabloid newspapers--all they lack is a bare-chested woman on page 3," he jibed.
Dr Brian Strom (University of Pennsylvania, Philadelphia) agrees. “Drugs are given because they have benefits. Where there’s a scare, people stop taking them. So you can do more harm than good if the scare is not based on correct information. I do believe this meta-analysis should have been published, but a less sensational editorial would have been better," he told heartwire.
Dr Robert Califf (Duke University, Durham, NC) made the point that news reporting should follow scientific discussion on drug-safety issues, not precede it. “It would be better if we had a system of postmarketing signal detection in which signals were vetted scientifically rather than splashed over TV and newspapers. I can't help but wonder if the NEJM is functioning more like the mainstream press than a scientific journal at this point, since many potential peer reviewers seem to feel that Dr Nissen's analyses are missing key elements that could have been added."
Dr Darren McGuire (University of Texas Southwestern, Dallas) commented to heartwire: “All the sensationalism surrounding this observation has created unnecessary chaos and confusion at the patient level."
Dr David Nathan (Harvard Medical School, Boston, MA), who was one of the reviewers of the NEJM paper, is not so sure that people have overreacted. “Yes, this was an imperfect analysis. It can’t be looked at as definitive, but at the same time the findings shouldn’t be ignored," he told heartwire. “GlaxoSmithKline had the opportunity to collaborate, and they chose not to. They say they have more data, but why have they not published it? If they can produce convincing data, we can become more relaxed about this drug. But for the moment all we have is Nissen’s analysis," he added. “I’m advising patients to discuss this with their doctors--there are other choices for the treatment of diabetes. It certainly doesn’t make much sense to me to use a drug that is potentially cardiotoxic in a condition that causes heart disease. Given the choice of all the drugs available I would be very cautious about using this medicine," Nathan said.
Nissen sob o foco dos admiradores.
Destaquei a relação das 100 pessoas mais influentes da atualidade pelo Time magazine onde figurava Steven Nissen. Depois do caso Avandia, ele está novamente no foco da mídia e, também de seus "admiradores". Vejam, os comentários abaixo retirado do Heartwire, um boletim do Medscape.
Nissen: A public safety net?
Other media coverage surrounding the rosiglitazone saga has focused on Nissen himself. The WSJ chronicled the background to the current study, noting that Nissen first became interested in rosiglitazone after finding that cardiovascular side effects were an issue with a related drug, muraglitazar. After publishing these findings, he received an email from a diabetes expert suggesting that rosiglitazone may have similar issues. Then last year, after seeing signs of cardiovascular problems in the DREAM and ADOPT studies, he started searching for more data, which he found on the FDA and GlaxoSmithKline websites. Cleveland Clinic statistician Kathy Wolski, who helped Nissen with the analysis, describes him in the WSJ article as “a dog with a bone" in his determination to investigate this issue.
As Nissen was also involved in the downfall of Vioxx (rofecoxib, Merck), he is gaining somewhat of a reputation as a drug watchdog. An Associated Press report describes Nissen as a “public safety net," adding: "As criticism of the FDA mounts, Nissen, aided by powerful medical journals and government officials, has become a de facto drug regulator." But one blogger on the WSJ site has a less charitable take on Nissen’s actions, noting that his unfavorable studies are focused on drugs and companies that are not supporting large trials with the Cleveland Clinic [5]. “Wake up pharmaceutical companies. . . . If you don’t hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and company," he jests.
Other media coverage surrounding the rosiglitazone saga has focused on Nissen himself. The WSJ chronicled the background to the current study, noting that Nissen first became interested in rosiglitazone after finding that cardiovascular side effects were an issue with a related drug, muraglitazar. After publishing these findings, he received an email from a diabetes expert suggesting that rosiglitazone may have similar issues. Then last year, after seeing signs of cardiovascular problems in the DREAM and ADOPT studies, he started searching for more data, which he found on the FDA and GlaxoSmithKline websites. Cleveland Clinic statistician Kathy Wolski, who helped Nissen with the analysis, describes him in the WSJ article as “a dog with a bone" in his determination to investigate this issue.
As Nissen was also involved in the downfall of Vioxx (rofecoxib, Merck), he is gaining somewhat of a reputation as a drug watchdog. An Associated Press report describes Nissen as a “public safety net," adding: "As criticism of the FDA mounts, Nissen, aided by powerful medical journals and government officials, has become a de facto drug regulator." But one blogger on the WSJ site has a less charitable take on Nissen’s actions, noting that his unfavorable studies are focused on drugs and companies that are not supporting large trials with the Cleveland Clinic [5]. “Wake up pharmaceutical companies. . . . If you don’t hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and company," he jests.
Avandia: Public Citizen se manifesta porque o risco seria conhecido há 5 anos
Letter Demonstrating that the FDA Knew About Avandia Dangers, Urging Action (HRG Publications #1812)
May 22, 2007
Andrew von Eschenbach, M.D., Commissioner U.S. Food and Drug AdministrationFood and Drug Administration5600 Fishers Lane Rockville, MD 20857
Dear Dr. von Eschenbach:
We have obtained an internal FDA memo dated almost five years ago concerning heart failure from Avandia and Actos (the other widely-prescribed glitazone drug for diabetes). The July 16, 2002 memo from FDA staff in the Division of Drug Risk Evaluation evaluated cases of heart failure reported to the FDA during the first two years of marketing that were serious enough to require hospitalization.[1] Their analysis of these adverse reaction reports found 47 cases in which the use of Avandia (25 cases) and Actos (22 cases) resulted in hospitalization for heart failure. In the majority of these cases, the heart failure improved with the cessation of treatment with these drugs, further evidence of their role in causing heart failure.
In their memo, the FDA scientists recommended that both labels “should include mention of these postmarketing reports.” They also recommended “a Phase IV cohort study to evaluate possible increased risk of incident CHF” [congestive heart failure]. At the time of this memo, the labeling for these drugs merely stated that:
WARNINGS
Cardiac Failure and Other Cardiac Effects: AVANDIA [or ACTOS], like other thiazolidinediones, alone or in combination with other antidiabetic agents, can cause fluid retention, which may exacerbate or lead to heart failure. Patients should be observed for signs and symptoms of heart failure. In combination with insulin, thiazolidinediones may also increase the risk of other cardiovascular adverse events. AVANDIA [or ACTOS] should be discontinued if any deterioration in cardiac status occurs.[2]
Despite this 2002 recommendation to mention post-marketing cases of heart failure and the fact that there are now a total of 1182 cases reported to the FDA with these two drugs (689 for Avandia, 493 for Actos; 803 involving hospitalization—415 for Avandia, 388 for Actos)[3], the current labeling for the drugs still starts with the identical warning.[4]
There continues to be no mention of the large and increasing number of post-marketing reports of heart failure, which was the explicit recommendation in the 2002 internal FDA memo.
The importance of the relationship between heart failure and heart attacks (myocardial infarction) is discussed in the New England Journal of Medicine article posted yesterday: “Rosiglitazone and other thiazolidinediones are known to precipitate congestive heart failure in susceptible patients. Congestive heart failure is a physiological state that is associated with an increased intravascular volume…In susceptible patients, an increase in myocardial oxygen demand could theoretically provoke ischemic events [such as myocardial infarctions].”[5]
The failure of the FDA to act on the recommendations made almost five years ago by its Division of Drug Risk Evaluation is yet another example (e.g.,Rezulin, Vioxx) in which the conclusions of employees engaged in post-market drug safety review are not taken seriously enough or addressed soon enough. As a result, millions of people are prescribed drugs, to the detriment of their health, whose risks are dangerously understated. Thus, instead of being prescribed safer, equally or more effective alternative drugs, patients’ lives continue to be put at risk. The magnitude of this problem can be seen in the enormous number of prescriptions for these drugs. The total number of prescriptions filled for Avandia and Actos in 2006 was 22 million (11 million for each).[6]
The current amount of data demonstrating cardiovascular risk of Avandia and Actos is certainly sufficient to at least label the drug as a last choice treatment and require a black box warning about the risks to the heart. Serious consideration should also be given as to why these drugs, which are supposed to decrease the cardiovascular complications of diabetes, are on the market at all since they actually increase these life-threatening problems.
Until this post-marketing drug safety part of CDER is made independent within the FDA of the rest of the Center for Drug Evaluation and Research, these life-taking mistakes will continue to occur. Such legislation was introduced by Senators Dodd and Grassley but is not included in the package of legislative reforms that have passed in the Senate and are likely to pass in the House.
We look forward to a prompt response to this letter.
Sidney M. Wolfe, MDElizabeth Barbehenn, Ph.D.Health Research Group at Public Citizen
cc: Congressmen Waxman, Dingell and Senators Grassley, Dodd
[1]Green L, Shaffer D, and Swartz L. Adverse Event—Congestive Heart Failure Requiring Hospitalization: Pioglitazone (Actos) , Rosiglitazone (Avandia) July 16, 2002.
[2]PDR, 2002, page 1493
[3]FDA AERS Data Base as of 9/30/06
[4]PDR, 2007, page 1387
[5] Nissen SE, Wolski K Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes N Engl J Med 2007;356.
[6]Drug Topics, Retail prescriptions filled during 2006.
May 22, 2007
Andrew von Eschenbach, M.D., Commissioner U.S. Food and Drug AdministrationFood and Drug Administration5600 Fishers Lane Rockville, MD 20857
Dear Dr. von Eschenbach:
We have obtained an internal FDA memo dated almost five years ago concerning heart failure from Avandia and Actos (the other widely-prescribed glitazone drug for diabetes). The July 16, 2002 memo from FDA staff in the Division of Drug Risk Evaluation evaluated cases of heart failure reported to the FDA during the first two years of marketing that were serious enough to require hospitalization.[1] Their analysis of these adverse reaction reports found 47 cases in which the use of Avandia (25 cases) and Actos (22 cases) resulted in hospitalization for heart failure. In the majority of these cases, the heart failure improved with the cessation of treatment with these drugs, further evidence of their role in causing heart failure.
In their memo, the FDA scientists recommended that both labels “should include mention of these postmarketing reports.” They also recommended “a Phase IV cohort study to evaluate possible increased risk of incident CHF” [congestive heart failure]. At the time of this memo, the labeling for these drugs merely stated that:
WARNINGS
Cardiac Failure and Other Cardiac Effects: AVANDIA [or ACTOS], like other thiazolidinediones, alone or in combination with other antidiabetic agents, can cause fluid retention, which may exacerbate or lead to heart failure. Patients should be observed for signs and symptoms of heart failure. In combination with insulin, thiazolidinediones may also increase the risk of other cardiovascular adverse events. AVANDIA [or ACTOS] should be discontinued if any deterioration in cardiac status occurs.[2]
Despite this 2002 recommendation to mention post-marketing cases of heart failure and the fact that there are now a total of 1182 cases reported to the FDA with these two drugs (689 for Avandia, 493 for Actos; 803 involving hospitalization—415 for Avandia, 388 for Actos)[3], the current labeling for the drugs still starts with the identical warning.[4]
There continues to be no mention of the large and increasing number of post-marketing reports of heart failure, which was the explicit recommendation in the 2002 internal FDA memo.
The importance of the relationship between heart failure and heart attacks (myocardial infarction) is discussed in the New England Journal of Medicine article posted yesterday: “Rosiglitazone and other thiazolidinediones are known to precipitate congestive heart failure in susceptible patients. Congestive heart failure is a physiological state that is associated with an increased intravascular volume…In susceptible patients, an increase in myocardial oxygen demand could theoretically provoke ischemic events [such as myocardial infarctions].”[5]
The failure of the FDA to act on the recommendations made almost five years ago by its Division of Drug Risk Evaluation is yet another example (e.g.,Rezulin, Vioxx) in which the conclusions of employees engaged in post-market drug safety review are not taken seriously enough or addressed soon enough. As a result, millions of people are prescribed drugs, to the detriment of their health, whose risks are dangerously understated. Thus, instead of being prescribed safer, equally or more effective alternative drugs, patients’ lives continue to be put at risk. The magnitude of this problem can be seen in the enormous number of prescriptions for these drugs. The total number of prescriptions filled for Avandia and Actos in 2006 was 22 million (11 million for each).[6]
The current amount of data demonstrating cardiovascular risk of Avandia and Actos is certainly sufficient to at least label the drug as a last choice treatment and require a black box warning about the risks to the heart. Serious consideration should also be given as to why these drugs, which are supposed to decrease the cardiovascular complications of diabetes, are on the market at all since they actually increase these life-threatening problems.
Until this post-marketing drug safety part of CDER is made independent within the FDA of the rest of the Center for Drug Evaluation and Research, these life-taking mistakes will continue to occur. Such legislation was introduced by Senators Dodd and Grassley but is not included in the package of legislative reforms that have passed in the Senate and are likely to pass in the House.
We look forward to a prompt response to this letter.
Sidney M. Wolfe, MDElizabeth Barbehenn, Ph.D.Health Research Group at Public Citizen
cc: Congressmen Waxman, Dingell and Senators Grassley, Dodd
[1]Green L, Shaffer D, and Swartz L. Adverse Event—Congestive Heart Failure Requiring Hospitalization: Pioglitazone (Actos) , Rosiglitazone (Avandia) July 16, 2002.
[2]PDR, 2002, page 1493
[3]FDA AERS Data Base as of 9/30/06
[4]PDR, 2007, page 1387
[5] Nissen SE, Wolski K Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes N Engl J Med 2007;356.
[6]Drug Topics, Retail prescriptions filled during 2006.
Transparência e Inteligência: a fase dos dados públicos
No episódio do mensalão, um dos envolvidos tornou célebre a frase: “transparência demais é burrice”. No caso Avandia, parece que esse foi o caso, com uma tinta de ironia, por favor. Explico, depois de uma disputa judicial com o o Estado de Nova Iorque, a Glaxo Smith Kline comprometeu-se a divulgar os resultados de todos os estudos relativos aos seus produtos. A partir desses dados foi possível, o cálculo do risco do medicamento. Ao contrário da frase cínica acima reproduzida, o fato mostra a importância da internet e do controle social sobre produtos de interesse coletivo, que não eram questionados tão rapidamente como agora. Que se torne obrigatória a divulgação de todos os resultados de pesquisas na web, incluindo os da indústria, como os originados por fundos públicos. Nesse último caso haveria um período de tempo para que os dados fossem publicados em revista com revisão por pares. Abaixo, artigo do The New York Times explicando o ocorrido entre os dados da Glaxo e a publicação no The New England Journal of Medicine.
For Drug Makers, a Downside to Full Disclosure
When GlaxoSmithKline settled a lawsuit three years ago with the State of New York over the antidepressant medication Paxil, the company agreed to take an unusual step: publicly disclosing the results of its clinical trials for Paxil and other drugs. The company, which was criticized at the time for failing to publicize all pediatric trials of Paxil, not just the positive ones, made good on its promise. The first posting on a new Web site was about 65 studies involving its popular diabetes drug, Avandia. This week, GlaxoSmithKline learned what that greater disclosure could mean. A cardiologist at the Cleveland Clinic, Dr. Steven Nissen, stumbled onto the Glaxo Web site while researching Avandia last April. He and a colleague quickly analyzed the data, and on Monday, The New England Journal of Medicine released its finding that Avandia posed a heightened cardiac risk. “It was a treasure trove,” Dr. Nissen said about the Web site. GlaxoSmithKline has disputed the journal’s interpretation. Officials with the Food and Drug Administration said they were reviewing whether to take any action on Avandia. Whatever the drug’s fate, the episode is likely to fuel efforts by some medical experts, including Dr. Nissen, to persuade lawmakers to require makers of drugs and medical devices to disclose study results publicly. Currently, producers are not required to do so, but Congress is considering legislating a requirement. Many companies besides GlaxoSmithKline already post results from some studies or trials on their Web sites, or one operated by the Pharmaceutical Research and Manufacturers Association, a trade group in Washington. Dr. Bruce M. Psaty, a cardiologist at the University of Washington, said that having such information can play a critical role, as the case of Avandia suggests, in spotting signals of a drug’s possible dangers. Other experts have argued that the relative efficacy or cost of competing drugs can be compared only when all study results, rather simply those that a company chooses to publicize, are available. Studies have found that the vast majority of drug and medical device studies are never published in medical journals. “The more information, the better,” Dr. Psaty said. Dr. Ronald L. Krall, chief medical officer for Glaxo, said his company sharply disputed the methodology of Dr. Nissen’s study, and a top F.D.A. official said that the agency had previously informed doctors about Avandia’s heart risks. Dr. Krall said his company was aware when it created its database of study results a few years ago that it might lead to controversy. Other scientists might look at its data or choose to analyze it differently than company officials did, he said. “We are committed to the principle of transparency,” Dr. Krall added. “But we knew that when starting this, by putting the data in the public, many things could happen, some of which could be trouble.” Some experts also believe that releasing the results of hundreds of studies involving drugs or medical devices might create confusion and anxiety for patients who are typically not well prepared to understand the studies or to put them in context. “I would be very concerned about wholesale posting of thousands of clinical trials leading to mass confusion,” said Dr. Steven Galson, the director for the Center for Drug Evaluation and Research at the F.D.A.
For Drug Makers, a Downside to Full Disclosure
When GlaxoSmithKline settled a lawsuit three years ago with the State of New York over the antidepressant medication Paxil, the company agreed to take an unusual step: publicly disclosing the results of its clinical trials for Paxil and other drugs. The company, which was criticized at the time for failing to publicize all pediatric trials of Paxil, not just the positive ones, made good on its promise. The first posting on a new Web site was about 65 studies involving its popular diabetes drug, Avandia. This week, GlaxoSmithKline learned what that greater disclosure could mean. A cardiologist at the Cleveland Clinic, Dr. Steven Nissen, stumbled onto the Glaxo Web site while researching Avandia last April. He and a colleague quickly analyzed the data, and on Monday, The New England Journal of Medicine released its finding that Avandia posed a heightened cardiac risk. “It was a treasure trove,” Dr. Nissen said about the Web site. GlaxoSmithKline has disputed the journal’s interpretation. Officials with the Food and Drug Administration said they were reviewing whether to take any action on Avandia. Whatever the drug’s fate, the episode is likely to fuel efforts by some medical experts, including Dr. Nissen, to persuade lawmakers to require makers of drugs and medical devices to disclose study results publicly. Currently, producers are not required to do so, but Congress is considering legislating a requirement. Many companies besides GlaxoSmithKline already post results from some studies or trials on their Web sites, or one operated by the Pharmaceutical Research and Manufacturers Association, a trade group in Washington. Dr. Bruce M. Psaty, a cardiologist at the University of Washington, said that having such information can play a critical role, as the case of Avandia suggests, in spotting signals of a drug’s possible dangers. Other experts have argued that the relative efficacy or cost of competing drugs can be compared only when all study results, rather simply those that a company chooses to publicize, are available. Studies have found that the vast majority of drug and medical device studies are never published in medical journals. “The more information, the better,” Dr. Psaty said. Dr. Ronald L. Krall, chief medical officer for Glaxo, said his company sharply disputed the methodology of Dr. Nissen’s study, and a top F.D.A. official said that the agency had previously informed doctors about Avandia’s heart risks. Dr. Krall said his company was aware when it created its database of study results a few years ago that it might lead to controversy. Other scientists might look at its data or choose to analyze it differently than company officials did, he said. “We are committed to the principle of transparency,” Dr. Krall added. “But we knew that when starting this, by putting the data in the public, many things could happen, some of which could be trouble.” Some experts also believe that releasing the results of hundreds of studies involving drugs or medical devices might create confusion and anxiety for patients who are typically not well prepared to understand the studies or to put them in context. “I would be very concerned about wholesale posting of thousands of clinical trials leading to mass confusion,” said Dr. Steven Galson, the director for the Center for Drug Evaluation and Research at the F.D.A.
quarta-feira, 23 de maio de 2007
Avandia: EMEA e FDA não estão surpresas
A EMEA - agência européia equivalente ao FDA americano e ANVISA brasileiro - manifestou-se sobre o caso Avandia, informando que não há surpresa no publicado e, que o medicamento encontra-se sobre vigilância da agência, que reconhece o aumento de doença isquêmica cardíaca.
Reproduzo, a seguir , em negrito a declaração da EMEA:
When rosiglitazone was first authorised in the EU in 2000, it was contraindicated in patients with a history of cardiac failure. Since then, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has kept rosiglitazone under close surveillance for cardiovascular effects (cardiac failure and other cardiac disorders including myocardial infarction). The majority of the studies included in the NEJM paper have already been assessed by the CHMP. The EU product information was updated in September 2006 with information about the risk of cardiac ischaemic events.
Pergunto porque a agência não se manifestou anteriormente?When rosiglitazone was first authorised in the EU in 2000, it was contraindicated in patients with a history of cardiac failure. Since then, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has kept rosiglitazone under close surveillance for cardiovascular effects (cardiac failure and other cardiac disorders including myocardial infarction). The majority of the studies included in the NEJM paper have already been assessed by the CHMP. The EU product information was updated in September 2006 with information about the risk of cardiac ischaemic events.
O FDA também se manifestou com declaração contraditória onde ora afirma que novas análises do estudo DREAM e de outro em andamento não revelaram risco (o DREAM não tinha revelado risco, não entendi essa menção) ou então declara que já mudara a bula do Avandia devido ao seguinte fato relatado pela própria empresa
Recently, the manufacturer of Avandia provided FDA with a pooled analysis (meta analysis) of 42 randomized, controlled clinical trials in which Avandia was compared to either placebo or other anti-diabetic therapies in patients with type 2 diabetes. The pooled analysis suggested that patients receiving short-term (most studies were 6-months duration) treatment with Avandia may have a 30-40 percent greater risk of heart attack and other heart-related adverse events than patients treated with placebo or other anti-diabetic therapy. These data, if confirmed, would be of significant concern since patients with diabetes are already at an increased risk of heart disease.
Pesquisa experimental em Olinda
O Secretário Municipal de Olinda se realizou pesquisa - auto-hemoterapia - em contrariedade ao estabelecido pela sociedade de especialidade, CRM e ANVISA. Se ele realizou sem autorização de Comissão de Ética em Pesquisa estará em péssima situação em todas as esferas na qual ele for julgado. A reportagem poderia ao menos informar se houve ou não autorização por alguma CEP autorizada pelo Conselho Nacional de Ética em Pesquisa do Conselho Nacional de Saúde. A sua defesa no texto foi pífia. Atenção ANVISA: moratória para produtos da China.
Ração para gatos e cães nos Estados Unidos, xarope no Panamá, agora pasta de dente na Republica Dominicana. Todos casos com dietileno glicol originados de produção na China. Abaixo, trecho de reportagem do The New York Times.
China Investigates Contaminated Toothpaste
By DAVID BARBOZA and WALT BOGDANICH Published: May 22, 2007
DANYANG, China, May 21 — Chinese authorities are investigating whether two companies from this coastal region exported tainted toothpaste as more contaminated product, including some made for children, has turned up in Latin America.A team of government investigators arrived here Sunday afternoon and closed the factory of the Danyang City Success Household Chemical Company, a small building housing about 30 workers in a nearby village, according to villagers and one factory worker. The government also questioned the manager of another toothpaste maker, Goldcredit International Trading, which is in Wuxi, about an hour’s drive southeast of here. No tainted toothpaste has been found in the United States, but a spokesman for the Food and Drug Administration said yesterday that the agency would be taking “a hard look” at whether to issue an import alert. Authorities in the Dominican Republic said they seized 36,000 tubes of toothpaste suspected of containing diethylene glycol, an industrial solvent and prime ingredient in some antifreeze. Included were tubes of toothpaste marketed for children with bubble gum and strawberry flavors sold under the name of “Mr. Cool Junior.” Toothpaste containing the toxic solvent was also found in Panama and Australia in the last week. Bautista Rojas Gómez, the secretary of health of the Dominican Republic, said the toothpaste, with diethylene glycol listed as an ingredient, was found in stores and warehouses across the country, including near the Haitian border. Diethylene glycol is the same poison that the Panamanian government unwittingly mixed into cold medicine last year, killing at least 100 people. In that case, the poison falsely labeled as glycerin, a harmless syrup, originated in China, shipping records show. Diethylene glycol is generally less expensive than its chemical cousin glycerin. Panamanian authorities said they believed the tainted toothpaste found in their country, containing up to 4.6 percent diethylene glycol, came from China. Executives from both companies under investigation in China denied in interviews on Monday that they had exported any toothpaste containing diethylene glycol to Panama. “We didn’t do this; we didn’t make the bad stuff,” said Shi Lei, a manager at Danyang City Success. “It was probably someone else." But Ms. Shi and other toothpaste makers in this region said that diethylene glycol had been used in toothpaste in China for years and that producers believed it was not very harmful. Government investigators arrived here just days after customs officials in Panama said that they had discovered diethylene glycol in 6,000 tubes of toothpaste. The toothpaste was being sold under the English brand names Mr. Cool and Excel. There have been no reports of deaths tied to toothpaste containing the chemical
By DAVID BARBOZA and WALT BOGDANICH Published: May 22, 2007
DANYANG, China, May 21 — Chinese authorities are investigating whether two companies from this coastal region exported tainted toothpaste as more contaminated product, including some made for children, has turned up in Latin America.A team of government investigators arrived here Sunday afternoon and closed the factory of the Danyang City Success Household Chemical Company, a small building housing about 30 workers in a nearby village, according to villagers and one factory worker. The government also questioned the manager of another toothpaste maker, Goldcredit International Trading, which is in Wuxi, about an hour’s drive southeast of here. No tainted toothpaste has been found in the United States, but a spokesman for the Food and Drug Administration said yesterday that the agency would be taking “a hard look” at whether to issue an import alert. Authorities in the Dominican Republic said they seized 36,000 tubes of toothpaste suspected of containing diethylene glycol, an industrial solvent and prime ingredient in some antifreeze. Included were tubes of toothpaste marketed for children with bubble gum and strawberry flavors sold under the name of “Mr. Cool Junior.” Toothpaste containing the toxic solvent was also found in Panama and Australia in the last week. Bautista Rojas Gómez, the secretary of health of the Dominican Republic, said the toothpaste, with diethylene glycol listed as an ingredient, was found in stores and warehouses across the country, including near the Haitian border. Diethylene glycol is the same poison that the Panamanian government unwittingly mixed into cold medicine last year, killing at least 100 people. In that case, the poison falsely labeled as glycerin, a harmless syrup, originated in China, shipping records show. Diethylene glycol is generally less expensive than its chemical cousin glycerin. Panamanian authorities said they believed the tainted toothpaste found in their country, containing up to 4.6 percent diethylene glycol, came from China. Executives from both companies under investigation in China denied in interviews on Monday that they had exported any toothpaste containing diethylene glycol to Panama. “We didn’t do this; we didn’t make the bad stuff,” said Shi Lei, a manager at Danyang City Success. “It was probably someone else." But Ms. Shi and other toothpaste makers in this region said that diethylene glycol had been used in toothpaste in China for years and that producers believed it was not very harmful. Government investigators arrived here just days after customs officials in Panama said that they had discovered diethylene glycol in 6,000 tubes of toothpaste. The toothpaste was being sold under the English brand names Mr. Cool and Excel. There have been no reports of deaths tied to toothpaste containing the chemical
Orquídea, beija-flores brasileiros e malária: edição de JAMA
Esse lindo quadro a óleo de Martin Johnson Heade (1819-1904) chama-se Cattleya Orchid and Three Brazilian Hummingbirds, 1871, encontra-se na National Gallery of Art de Washington. Ele está na capa da edição dessa semana do JAMA inteiramente devotada ao tema "malária", uma das doenças mais intrigantes que ainda ceifa muitas vidas.terça-feira, 22 de maio de 2007
Repercussão do caso Avandia
Finalmente, mais de 24 horas depois de ter tido acesso ao artigo e editorial referente ao risco cardiovascular da Avandia consegui ler ambos. Apesar de não ser fanático por metanálise, o artigo é consistente. O editorial é um verdadeiro torpedo contra o FDA pela aprovação sem critérios mais rígidos. Assisti entrevista com Steve Nissen onde ele afirma que os dados obtidos não eram os melhores (explico abaixo), somente uma síntese publicada e disponível na web. A Glaxo há três anos foi acusada de esconder dados de medicação psiquiátria e, partir daí passou a mostrar todos os estudos referentes aos seus medicos. A origem dos dados desse trabalho vieram daí. Por isso, intriga muito aos editorialistas - e, também a mim - porque a empresa com dados mais fortes (explico abaixo) não os publicou? E, porque o FDA não exigiu que isso fosse feito.
Quanto ao prêmio Zeca Pagodinho, quesito diabetes, vários leitores de blogues americanos concorreram, mas somente brasileiros são elegíveis. Vamos ver os jornais de amanhã. Porém, paro por aqui porque acho que haverá nada mais significativo.
explicação técnica: a melhor forma de calcular risco é saber não somente o número de participantes que sofreram infarto ou morreram, mas também por quanto tempo o fizeram. os dados disponíveis não mostram o tempo de exposição, por isso considerei que Nissen trabalhou com informação mais fraca, o que para ele foi uma força.
O último catedrático: severo e culto
O adeus ao último catedrático de clínica médica da USP e um dos fundadores da cardiologia brasileira que descreveu a doença reumática em nosso país.A farmacogenômica, CNTBio e o futuro da Big Pharma
O presidente mundial da Eli Lilly em entrevista a IstoÉ Dinheiro abriu o jogo: estamos em outra, adeus commodities, química fina, estamos na biotecnologia. Eu tinha afirmado que essa era uma tendência mais européia do americana, mas a Eli Lilly está de fato mudando mudança.
O uso da farmacogenômica estimulará muito os compostos biológicos e dirigirá o tratamento pelos compostos químicos e, na opinião de vários representará realmente - desculpem o chavão - uma mudança de paradigma.
De certa forma, a Big Pharma será a Big Biotech com os avanços da genômica que permitirão particularizar o tratamento. Por isso, problema no Brasil está na CNTBio com o controle da biotecnologia por ONGs - talvez não tão ingênuas - do que a política de aids do Ministério da Saúde que levou ao licenciamento compulsório do efavirenz.
Ele quer reinventar o remédio. IstoE Dinheiro. por Joaquim Castanheira.
Na semana passada, o executivo Sidney Taurel, presidente mundial do Eli Lilly, desembarcou no Brasil. Foi uma visita discreta, praticamente sem compromissos externos, como costuma ocorrer com executivos de alto escalão como ele. "Vim conhecer o passado e falar do futuro", disse ele, em entrevista exclusiva à DINHEIRO. Primeiro, Taurel ouviu em detalhes os resultados da revolução que catapultou a filial brasileira da 30ª para a 15ª posição no ranking do setor farmacêutico nacional. O Lilly vendeu negócios, abandonou medicamentos tradicionais como antibióticos e investiu em produtos inovadores como Ciallis e Ziprexa. No capítulo dedicado ao futuro, Taurel mais falou do que ouviu. E apresentou seu plano daquilo que poderia ser chamado da "reinvenção dos remédios". Nos últimos anos, o Lilly trabalha em um novo modelo de negócios, cujos resultados, em toda sua plenitude, deverão aparecer em 15 a 20 anos. Nesse novo formato, os medicamentos serão desenvolvidos para atacar aspectos específicos de cada doença, e não a enfermidade como um todo. "É a terapia sob medida, a medicação personalizada", afirma Taurel. "Só 20% de nossos negócios trabalham dentro desse conceito." "Os remédios atuais funcionam, em média, para apenas 50% dos pacientes", diz. Para algumas enfermidades, como câncer, esse índice é reduzido, cerca de 20%. Já para excesso de colesterol, sobe para 80%. "Para os demais pacientes, é dinheiro jogado fora", afirma ele. O tratamento revela-se, na melhor das hipóteses, inócuo. Pior: em alguns casos, provoca efeitos colaterais. "Não temos hoje ferramentas para determinar que pacientes serão beneficiados pelo produto", explica Taurel. Por quê? Por dois motivos, completa o presidente da filial brasileira, Gaetano Grupi. Um: a diversidade genética do ser humano. Dois: a ausência de biomarcadores confiáveis. Traduzindo: biomarcadores são substâncias que auxiliam na identificação de enfermidades - o nível de colesterol no sangue, por exemplo. Assim, apenas o uso do medicamento revela quem pode ou não utilizá-lo. "Queremos nos antecipar e definir os beneficiários antes de o produto chegar às farmácias", diz Taurel. " Só 20% de nossos negócios trabalham de acordo com o novo conceito "Sidney Taurel Essa postura muda profundamente a forma de uma empresa desenvolver e comercializar remédios. "Às vezes, vamos nos recusar a vender para alguns pacientes, pois saberemos que não terá utilidade para ele", afirma Taurel. Não, o Lilly não gosta de jogar dinheiro fora. Há por trás desse modelo uma lógica empresarial diferente da atual. O laboratório acredita que, dessa forma, conquistará uma participação de mercado muito superior entre os pacientes que se beneficiarão com aquele remédio."Eles vão preferir nosso produto, já que terão certeza de sua eficácia", diz Grupi. "Assim, enfrentaremos nossos concorrentes." Há um outro dividendo que o Lilly espera contabilizar. "Os médicos terão mais confiança em nós, devido à nossa transparência", aposta Taurel.
Na semana passada, o executivo Sidney Taurel, presidente mundial do Eli Lilly, desembarcou no Brasil. Foi uma visita discreta, praticamente sem compromissos externos, como costuma ocorrer com executivos de alto escalão como ele. "Vim conhecer o passado e falar do futuro", disse ele, em entrevista exclusiva à DINHEIRO. Primeiro, Taurel ouviu em detalhes os resultados da revolução que catapultou a filial brasileira da 30ª para a 15ª posição no ranking do setor farmacêutico nacional. O Lilly vendeu negócios, abandonou medicamentos tradicionais como antibióticos e investiu em produtos inovadores como Ciallis e Ziprexa. No capítulo dedicado ao futuro, Taurel mais falou do que ouviu. E apresentou seu plano daquilo que poderia ser chamado da "reinvenção dos remédios". Nos últimos anos, o Lilly trabalha em um novo modelo de negócios, cujos resultados, em toda sua plenitude, deverão aparecer em 15 a 20 anos. Nesse novo formato, os medicamentos serão desenvolvidos para atacar aspectos específicos de cada doença, e não a enfermidade como um todo. "É a terapia sob medida, a medicação personalizada", afirma Taurel. "Só 20% de nossos negócios trabalham dentro desse conceito." "Os remédios atuais funcionam, em média, para apenas 50% dos pacientes", diz. Para algumas enfermidades, como câncer, esse índice é reduzido, cerca de 20%. Já para excesso de colesterol, sobe para 80%. "Para os demais pacientes, é dinheiro jogado fora", afirma ele. O tratamento revela-se, na melhor das hipóteses, inócuo. Pior: em alguns casos, provoca efeitos colaterais. "Não temos hoje ferramentas para determinar que pacientes serão beneficiados pelo produto", explica Taurel. Por quê? Por dois motivos, completa o presidente da filial brasileira, Gaetano Grupi. Um: a diversidade genética do ser humano. Dois: a ausência de biomarcadores confiáveis. Traduzindo: biomarcadores são substâncias que auxiliam na identificação de enfermidades - o nível de colesterol no sangue, por exemplo. Assim, apenas o uso do medicamento revela quem pode ou não utilizá-lo. "Queremos nos antecipar e definir os beneficiários antes de o produto chegar às farmácias", diz Taurel. " Só 20% de nossos negócios trabalham de acordo com o novo conceito "Sidney Taurel Essa postura muda profundamente a forma de uma empresa desenvolver e comercializar remédios. "Às vezes, vamos nos recusar a vender para alguns pacientes, pois saberemos que não terá utilidade para ele", afirma Taurel. Não, o Lilly não gosta de jogar dinheiro fora. Há por trás desse modelo uma lógica empresarial diferente da atual. O laboratório acredita que, dessa forma, conquistará uma participação de mercado muito superior entre os pacientes que se beneficiarão com aquele remédio."Eles vão preferir nosso produto, já que terão certeza de sua eficácia", diz Grupi. "Assim, enfrentaremos nossos concorrentes." Há um outro dividendo que o Lilly espera contabilizar. "Os médicos terão mais confiança em nós, devido à nossa transparência", aposta Taurel.
Avandia: leia The Wall Street Journal e vote no prêmio Zeca Pagodinho quesito diabetes.
A melhor cobertura sobre o tema encontra-se em jornal especializado em economia pelo motivo simples: a queda nas ações da Glaxo Smith Kline.
O tema Avandia já foi tratado aqui em 16.9.06 analisando o estudo básico para o Avandia. "Dream: o óbvio é comprovado para o diabetes". Nas próximas semanas, médicos que não têm a mínima idéia como organizar uma meta-análise, mas sabem muito bem como agradar uma empresa farmacêutica estarão dando entrevistas, fazendo palestras e outras coisas sobre a "segurança da Avandia". Aguardem a saraivada de intrigas contra Steven Nissen. Uma no blogue do WSJ diz que ele será o commissioner da FDA em um provável governo Hillary Clinton.
Aqui, no Brasil vamos ver quem vencerá o prêmio "Zeca Pagodinho" no quesito diabetes.
O controle da prescrição médica pela indústria farmacêutica.
The Washington Post noticia o problema sério do conhecimento da prescrição médica por parte da indústria farmacêutica. Vários estados americanos estão proibindo tal prática, mas há disputas judiciais importantes. A American Medical Association cuja revista - JAMA - defende princípios rígidos no contato com a indústria, não se envergonha de vender seu cadastro à indústria. Aqui, no Brasil a prática ocorre com a participação das farmácias que ao consta, fazem cópia de receitas. Uma situação a investigar.
Doctors, Legislators Resist Drugmakers' Prying Eyes
By Christopher LeeWashington Post Staff WriterTuesday, May 22, 2007; Page A01
Seattle pediatrician Rupin Thakkar's first inkling that the pharmaceutical industry was peering over his shoulder and into his prescription pad came in a letter from a drug representative about the generic drops Thakkar prescribes to treat infectious pinkeye.
In the letter, the salesperson wrote that Thakkar was causing his patients to miss more days of school than they would if he put them on Vigamox, a more expensive brand-name medicine made by Alcon Laboratories.
The law: Banned the sale or use of data on individual doctors' prescribing choices for marketing and other commercial purposes, while allowing it for research, law enforcement and patient education. The goal was to protect physician privacy and reduce health-care costs.
"My initial thought was 'How does she know what I'm prescribing?' " Thakkar said. "It feels intrusive. . . . I just feel strongly that medical encounters need to be private."
He is not alone. Many doctors object to drugmakers' common practice of contracting with data-mining companies to track exactly which medicines physicians prescribe and in what quantities -- information marketers and salespeople use to fine-tune their efforts. The industry defends the practice as a way of better educating physicians about new drugs. Now the issue is bubbling up in the political arena. Last year, New Hampshire became the first state to try to curtail the practice, but a federal district judge three weeks ago ruled the law unconstitutional. This year, more than a dozen states have considered similar legislation, according to the National Conference of State Legislatures. They include Arizona, Illinois, Kansas, Maine, Massachusetts, New York, Nevada, Rhode Island, Texas, Vermont and Washington, although the results so far have been limited. Bills are stalled in some states, and in others, such as Maryland and West Virginia, they did not pass at the committee level. The concerns are not merely about privacy. Proponents say using such detailed data for drug marketing serves mainly to influence physicians to prescribe more expensive medicines, not necessarily to provide the best treatment. "We don't like the practice, and we want it to stop," said Jean Silver-Isenstadt, executive director of the National Physicians Alliance, a two-year-old group with 10,000 members, most of them young doctors in training. (Thakkar is on the group's board of directors.) "We think it's a contaminant to the doctor-patient relationship, and it's driving up costs." The American Medical Association, a larger and far more established group, makes millions of dollars each year by helping data-mining companies link prescribing data to individual physicians. It does so by licensing access to the AMA Physician Masterfile, a database containing names, birth dates, educational background, specialties and addresses for more than 800,000 doctors. After complaints from some members, the AMA last year began allowing doctors to "opt out" and shield their individual prescribing information from salespeople, although drug companies can still get it. So far, 7,476 doctors have opted out, AMA officials said.
By Christopher LeeWashington Post Staff WriterTuesday, May 22, 2007; Page A01
Seattle pediatrician Rupin Thakkar's first inkling that the pharmaceutical industry was peering over his shoulder and into his prescription pad came in a letter from a drug representative about the generic drops Thakkar prescribes to treat infectious pinkeye.
In the letter, the salesperson wrote that Thakkar was causing his patients to miss more days of school than they would if he put them on Vigamox, a more expensive brand-name medicine made by Alcon Laboratories.
The law: Banned the sale or use of data on individual doctors' prescribing choices for marketing and other commercial purposes, while allowing it for research, law enforcement and patient education. The goal was to protect physician privacy and reduce health-care costs.
"My initial thought was 'How does she know what I'm prescribing?' " Thakkar said. "It feels intrusive. . . . I just feel strongly that medical encounters need to be private."
He is not alone. Many doctors object to drugmakers' common practice of contracting with data-mining companies to track exactly which medicines physicians prescribe and in what quantities -- information marketers and salespeople use to fine-tune their efforts. The industry defends the practice as a way of better educating physicians about new drugs. Now the issue is bubbling up in the political arena. Last year, New Hampshire became the first state to try to curtail the practice, but a federal district judge three weeks ago ruled the law unconstitutional. This year, more than a dozen states have considered similar legislation, according to the National Conference of State Legislatures. They include Arizona, Illinois, Kansas, Maine, Massachusetts, New York, Nevada, Rhode Island, Texas, Vermont and Washington, although the results so far have been limited. Bills are stalled in some states, and in others, such as Maryland and West Virginia, they did not pass at the committee level. The concerns are not merely about privacy. Proponents say using such detailed data for drug marketing serves mainly to influence physicians to prescribe more expensive medicines, not necessarily to provide the best treatment. "We don't like the practice, and we want it to stop," said Jean Silver-Isenstadt, executive director of the National Physicians Alliance, a two-year-old group with 10,000 members, most of them young doctors in training. (Thakkar is on the group's board of directors.) "We think it's a contaminant to the doctor-patient relationship, and it's driving up costs." The American Medical Association, a larger and far more established group, makes millions of dollars each year by helping data-mining companies link prescribing data to individual physicians. It does so by licensing access to the AMA Physician Masterfile, a database containing names, birth dates, educational background, specialties and addresses for more than 800,000 doctors. After complaints from some members, the AMA last year began allowing doctors to "opt out" and shield their individual prescribing information from salespeople, although drug companies can still get it. So far, 7,476 doctors have opted out, AMA officials said.
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