sexta-feira, 15 de junho de 2007

Nissen não é mágico

O blogueiro de The Scientist não perdou a incapacidade de Steven Nissen - autor da metanálise sobre o Avandia - em prever o futuro. O colega do The Wall Street Journal reproduziu o ocorrido cujo texto segue abaixo. Cleveland Clinic Cardiologist’s Crystal Ball Imperfect Posted by Scott Hensley The FDA advisory panel that just dissed Acomplia, Sanofi-Aventis’s weight-loss drug, dealt an indirect blow to a frequent and outspoken critic of the drug industry. The thumbs-down for Acomplia marks at least the second time in a year that Cleveland Clinic cardiologist Steven Nissen “has been wrong about the promise of new drugs,” writes Ivan Oransky on the blog of The Scientist today. Last October, Nissen (pictured, upper left) was part of a panel discussion that Oransky moderated at a meeting of health-care journalists in Cleveland. In preparation for the talk, Oransky asked the speakers to come with two ideas that the audience of reporters and editors might be interested in as potential stories. “Nissen brought two: Acomplia, which he said was a clever scientific idea and held real promise, and CETP inhibitors such as Pfizer’s torcetrapib,” he writes. “He was quite excited about both drugs, and was involved in trials of both at the time, which he disclosed.” The panel discussion took place on Friday, Oct. 27. Three days later, Pfizer disclosed information that heightened concerns about torcetrapib’s tendency to raise blood pressure in patients taking it. Afterwards, Nissen acknowledged the findings raised the hurdle for approval of the medicine. But Pfizer halted development of torcetrapib in early December after excess deaths were found in a 15,000-patient study of the medicine. The FDA advisors who voted down Acomplia yesterday dimmed the prospects for the drug being approved in the U.S. anytime soon. Plenty of people besides Nissen were hopeful about both Acomplia and torcetrapib. And nobody can know for sure about the hypothesized benefits and risks of an experimental medicine until the clinical data are in. Still, Oransky concludes: “I think it’s worth noting the record of someone whose pronouncements on drugs are so often held up by drug industry critics and that make media headlines.” The Health Blog called Nissen, who declined to comment.

quarta-feira, 13 de junho de 2007

O Yin e o Yang da regulação de medicamentos.

O The New York Times publicou um artigo com questionamento já abordado nesse blogue e, defendido por muitos pesquisadores e diretores clínicos da Big Pharma: não é possível liberar um medicamento novo com a velocidade exigida e que seja, ao mesmo tempo, seguro. Ponto final. Defendo também a Big Pharma na questão tempo de patente: o ideal é a contagem de tempo após a publicação de estudos de segurança e , não do registro do medicamento.
Outro problema decorrente dessa pressa é que medicamento com grande utilidade - mas, com prescrição mais restrita - foram "queimados" pelo risco apresentado em indicações de certa forma indevida.
O texto do NYT começa dessa forma:
Potentially Incompatible Goals at F.D.A. By GARDINER HARRISPublished: June 11, 2007 Safety and speed are the yin and yang of drug regulation. Patients want immediate access to breakthrough medicines but also want to believe the drugs are safe. These goals can be incompatible. Race a drug to market and much is likely to remain unknown when patients take it. Test a drug thoroughly to assess all possible risks and its release may be delayed by years.A series of drug-safety scandals has led many on Capitol Hill to question whether the Food and Drug Administration has failed to strike the right balance between speed and safety. A clear sign of this imbalance, these critics say, is the increasing number of F.D.A. drug-safety officers who say they have been punished or ignored after uncovering dangers of popular medicines.
Aqui se apresenta as origens da crise atual:
In the 1980s, the F.D.A. took nearly three years to approve most drugs. The AIDS crisis demonstrated that such long delays could condemn to death patients who might have been helped by recent scientific breakthroughs. F.D.A. managers said they did not have enough people to assess reviews more quickly. So in 1992, Congress helped the F.D.A. and the drug industry reach a deal. Companies agreed to pay millions of dollars in fees, and the F.D.A. guaranteed that drug reviews would be completed within a year or as little as six months for a life-saving medicine. At the time, it seemed a good solution. But the deal’s fine print soon came to haunt the agency. Drug makers refused to let their money pay for the routine monitoring of drugs’ safety once they were on the market. As the agency began to depend more and more on industry fees, those parts of the agency slowly withered.

O impacto da ideologização da ciência

O gráfico ao lado mostra o aumento da razão masculino/feminino de nascimento na Armênia, após a sua independência. A explicação é a seguinte: por ter forte apoio externo devido à diáspora armênia, houve entrada de muitos recursos e doações como aparelhos de ultra-som. Com o aborto permitido, houve um feminicídio em proporção maior que a chinesa. Tudo isso em um país com grau elevado de cultura, mas pertencente a um conjunto de países - a União Soviética - onde prevaleceu a ideologia sobre a ciência. Apesar do Sputinik. Esse é um pequeno exemplo de um artigo excelente publicado no International Journal of Epidemiology Cochrane on Communism: the influence of ideology on the search for evidenceMartin McKee. Acessível somente a assinantes ou aqueles com permissão da base CAPES de periódico. Abaixo, dois pequenos trecho do artigo.
In his seminal work Effectiveness and Efficiency,1 Archie Cochrane asked why, despite their enormous potential, randomized trials were much less widely used that they should be. At the time that he was writing, their geographical distribution was very uneven. He wrote ‘If some such index as the number of RCTs per 1,000 doctors per year for all the countries of the world were worked out, and a map of the world shaded according to the level of the index, one would see the UK in black, and scattered black patches in Scandinavia, the USA, and a few other countries. The rest would be nearly white. It appears in general that it is Catholicism, Communism, and underdevelopment that appear to be against RCTs. In underdeveloped countries this can be understood but what have Catholicism and Communism against RCTs?’

An example can be seen in Armenia. Shortly after gaining independence, Armenian physicians acquired large numbers of ultrasound machines, often benefiting from assistance from the extensive Armenian Diaspora. This was associated with a rapid rise in the male:female sex ratio to a level that now exceeds that in China. There are, however, many other examples. A recent study of obstetric care in a region near Moscow found that many of the obstetric interventions were ineffective, such as physical therapies based on light, electricity or magnetism, administered at some stage during pregnancy. Other treatments were unnecessarily unpleasant, such as the near universal practice of administering intra-muscular injections of vitamins. Yet, others were potentially harmful, such as the administration of diethylstilbestrol, even though it has been known since the 1960s that it causes vaginal cancer in those exposed in utero. Many of the drugs used, including a diverse range of infusions administered almost universally to pregnant women, have never been subject to rigorous evaluation.

terça-feira, 12 de junho de 2007

Avandia: tentativa de encerramento

Tentarei encerrar o caso Avandia porque já cansou. O próximo passo será a retirada do mercado ou a saída à francesa, visto que as prescrições se reduziram nos EUA em 15-20%. (ver reportagem do The Wall Street Journal) Os artigos publicados na semana passada no The New England Journal of Medicine ampliaram a crítica ao medicamento, ao contrário do esperado pela empresa ao liberar a análise preliminar do estudo Record cujo desfecho foi doença cardiovascular e, não normalização da glicemia. O estudo Record apresentado pela empresa como prova de que não há risco com o uso de Avandia, torna a sua prescrição como desnecessária. Afinal, se não não há redução do risco cardiovascular, qual a vantagem de se prescrever medicamento tão caro? Há problemas metodológicos que aumentam a limitação do estudo. Pior, Psaty e Furberg (em editorial no mesmo dia) adicionaram os dados publicados à metanálise original de Nissen (que originou o problema) e, mesmo assim há risco aumentado de infarto do miocárdio. Por último, não há qualquer lógica em corrigir a glicemia com medicamento que aumenta o risco (comprovado também no Record) de insuficiência cardíaca.

Senhor Yamada (ou equivalente) para Ministro da Saúde.

The Economist (edição de 09 a 15 de junho) apresenta reportagem sobre o que eles chamam de ataque à patentes da indústria farmacêutica. O artigo é bem ponderado com vários pontos de vistas, exceto a do governo brasileiro, visto que o foco é mais na Tailândia e na Índia. Porém, há uma frase de personagem já aqui citado, o senhor Tadataka Yamada, hoje diretor da Fundação Melinda e Bill Gates: “Brazil is not Rwanda, which cannot afford to pay”. Interessante, muito interessante, as análises vindas dessa Fundação. Quando convém aos interesses da Fundação, o Brasil é um país rural onde campeia parasitores sendo imposta a vacina jeca tatu para ancilostomíase. Em outro momento, onde a defesa dos interesses da Big Pharma é mais importante, o discurso muda o estágio de desenvolvimento do país é outro. Já discorri mais de uma vez sobre a vacina da ancilostomíase e o papel da Fundação Melinda e Bill Gates. (clique aqui) Discordo que os Institutos Rene Rachou (MG) e Butantan (SP) gastem tempo com essa proposta. Melhor seria se preocupar com o vírus sincicial respiratório cuja contaminação aflige milhões de crianças e aumentam consideravelmente a morbidade nessa época do ano.
Ou o Ministério da Saúde, Secretarias de Saúde e acadêmicos de uma forma geral estabelecem qual a agenda de prioridades de ações em saúde ou estaremos sendo dirigidos por pessoas como o senhor Yamada, ora na Glaxo Smith-Kline ora na Fundação Gates.