Nova forma de estimular a pesquisa na Big Pharma

A Big Pharma quando quer sabe inovar e dar a volta por cima. A maior delas, depois do tombo provocado pela Avandia. Agora estão estimulando a iniciativa de investigadores com capital da própria empresa. Isso mostra que o estímulo é para a biotecnologia, onde o pesquisador em pequenos laboratórios consegue resultados melhor do que aquele obtido em projetos grandes e custosos. Outra notícia é que a Glaxo está repassando sua linha de genérico em vários países para uma empresa sulafricana. Mais um dado mostrando que a química fina já era como o centro da atividade da indústria farmacêutica. Um ponto a ser muito bem debatido.

Three Big Moves for Glaxo.Posted by Jacob Goldstein Andrew Witty, GlaxoSmithKline’s new CEO, is starting to shake things up. A few key moves announced in the past day:A panel including a venture capitalist and the CEO of a biotech company will decide how to parcel out $1 billion a year in funding to Glaxo researchers, the Financial Times reports. “This will be analogous to a university spin-out going to a venture capitalist, and having to answer the questions of whether their strategy stacks up with the market place and is the team the right one to deliver,” Witty told the FT. Research teams will also be split into smaller units of five to 80 scientists.

Ex Big da Big Big Pharma desagrava epidemiologistas. E, agora speakers?

Imperdível a reportagem no The IN VIVO Blog sobre a saída de JP Garnier da Glaxo Smith Kline. Os pontos apresentados por ele decorrentes de vários problemas, mas principalmente do Avandia mostram o quanto a Big Pharma errou. Epidemiologistas estamos sendo desagravados pelo CEO da maior Big Pharma do ataque constante dos speakers da própria Big Pharma.

Há décadas que se critica o abuso dos "surrogate end-points". Leiam abaixo a opinião de Garnier sobre o uso da hemoglobina glicada como desfecho em oposição a um evento clínico como gangrena ou infarto do miocárdio. (clique aqui para ler a reportagem completa)

Expect to do more outcomes studies.“There will be more demands for outcome studies. People are even questioning whether hemoglobin A1c is a good indicator for diabetes. It is very easy to say well why don’t you do outcome studies and show us that over five or six years you can reduce the rate of gangrene and heart attacks and the like. Well, if we have to do that, it is going to be a long time before the product can hit the market. So we’re going to have to deal with this issue.”Once again, it is not just Avandia that supports that argument. Look at ENHANCE.

de volta, feliz 2008

Há 18 meses iniciei esse blogue. O objetivo era modesto, se modéstia não for termo incompatível à blogosfera. Recebi apoio de vários outros blogueiros que aumentaram a audiência e, tenho leitores fiéis na casa de duas centenas. Ao contrário, da blogosfera política, os leitores são civilizados e, na maioria enviam mensagens por email com críticas e sugestões. A avaliação desse período mostrou que fui um dos primeiros a mostrar a importância dos programas de saúde nas eleições americanas, a apresentar a absurda prisão de enfermeiras búlgaras na Líbia, a mostrar que a queda de homicídios é real e, reproduzir o noticiário de casos extremos, como o Avandia. Por outro lado, excedi um pouco em comentários sobre a política e entrei em questões pessoais. Claro, que estive há anos-luz de blogueiros que publicam foto de filhas, cadernos, relatos de filhas, netos e, discorrem sobre tudo e todos. Questões pessoais, definitivamente, são da esfera pessoal, por mais acaciano que seja essa afirmativa. O produto que continuarei a fazer é acadêmico, uma tentativa de traduzir a epidemiologia e a clínica, a outros setores que não os especialistas no assunto. Por isso, prescindirá de questões pessoais. Por último, cabe sempre insistir sobre o conflito de interesse. Minhas fontes de renda são o salário da Universidade, da bolsa do Conselho Nacional de Pesquisa e, de direitos autorais. Se, outra fonte surgir, os leitores saberão de imediato. Nesse ano, utilizarei o recurso Google Pages para permitir leitura mais dinâmica do blogue. Haverá comentários curtos com a ligação a textos longos. Em março, haverá uma página mais técnica denominada Clínica e Epidemiologia dirigida a profissionais, pesquisadores e estudantes das ciências da sáude.

em recesso, Avandia: transcrição de outro blogue

IN VIVO Blog Update Who's Sorry Now? Not Feeling So Good Edition Posted: 30 Jan 2008 11:50 AM CST Nature reports today that a peer reviewer for the New England Journal of Medicine leaked to GlaxoSmithKline that big old Avandia meta-analysis that has been the bane of their existence since it was released in May 2006. (Our coverage of the Avandia debacle can be found here.) University of Texas Health Science Center professor of epidemiology Steven Haffner, MD, explained to Nature: "Why I sent it is a mystery. I don't really understand it. I wasn't feeling well. It was bad judgement." Brian Vastag writes in Nature that Haffner faxed the article 17 days ahead of publication to GSK's Alexander Cobitz, whom he had worked with on an earlier trial of Avandia. What happens from there is unclear--though it's not like GSK effectively got out in front of the news, the 17-days head start may have helped them provide a relatively prompt interim analysis of its RECORD study, which was published in the NEJM in June to try to stop the bleeding. We will likely have more on this later, once the dust settles. For now, we bring you another edition of "Who's Sorry Now?" Steven Haffner to NEJM: Sorry I leaked the Avandia study, but i had a serious cold that day. Senator Grassley's office to Nature: Sorry we broke your embargo on the Avandia news today, but we aren't feeling so hot today ourselves. American Heart Association and American College of Cardiology to patients: sorry we forgot to disclose our potential financial ties to Merck and Schering-Plough, but there's a wicked flu going around the office. Phillies to Mets: Sorry you're spending all that money on Santana, but you're still not winning the NL East this year. Cough. © Copyright 2008 Windhover Information Inc. www.windhover.com/blog

Blogue em recesso

O final de ano obriga a muitas coisas: entregar relatórios, enviar textos atrasados, corrigir teses e, como não poderiam faltar: as festas, os almoços, e as confraternizações.

As coisas no Brasil esfriam, mas se mantém acesa no hemisfério norte. Mesmo assim, é o momento do recesso.

Um momento de reflexão, de ler aquela montanha de livros e textos que li apressadamente e, recomendei.

Agradeço a atenção da minha quase duas centenas de leitores diários nesse ano de 2007. Em fevereiro de 2008 voltarei normalmente, exceto algo muito excepcional ocorra, tal como um novo caso Avandia que rendeu a maior audiência do blogue em 2007.

Até o final do ano farei uma postagem com um balanço do ano.

Feliz Natal e Ótimo 2008.

Avandia: agora osteoporose

Quando uma empresa força demais a indicação de um medicamento, ocorre uma reação inversa, que muitas vezes é desproporcional ao potencial dano do medicamento. Um exemplo é o relatado abaixo pela Associated Press e, repetido em todos os jornais do planeta. Apesar, da empresa reconhecer a possibilidade de aumento de fraturas, o objeto de discussão - osteoporose - não é objeto de preocupação em termos clínicos. Primeiro, os dados foram obtidos em animais. Segundo, o risco cardíaco é mais importante do que o aumento de risco de osteoporose. Por último, notem que o pesquisador que identificou o mecanismo em ratos de forma súbita já indica ações médicas a longo prazo.

Popular Diabetes Drug May Increase Osteoporosis Associated PressDecember 2, 2007 1:29 p.m. WASHINGTON -- The popular diabetes drug marketed as Avandia may increase bone thinning, a discovery that could help explain why diabetics can have an increased risk of fractures. New research raises the possibility that long-term treatment with rosiglitazone, as Avandia is also called, could lead to osteoporosis. The diabetes drug is used to improved response to insulin. While bones seem solid, they constantly are being broken down and rebuilt by the body. Researchers found that in mice, the drug increased the activity of the cells that degrade bones, according to a report in this week's online issue of Nature Medicine. Avandia recently was labeled with warnings about the risk of heart failure in some patients. GlaxoSmithKline, which markets the drug, already has acknowledged that a study found a higher risk of fractures among women who take the drug. But this report is the first to attempt to explain the link between the drug and fractures. The finding "has led to a better understanding of the challenges associated with long-term treatment of patients with Type II diabetes," said Ronald M. Evans of the Salk Institute for Biological Studies in La Jolla, Calif., lead author of the report. "It also provides a basis for the development of a "next generation" of drug that can specifically dial out this side effect and a new insight into a previously unrecognized aspect of bone physiology that has important medical consequences," he said in an interview via e-mail. Nearly 21 million people in the United States have diabetes. Rosiglitazone is widely used in people with Type II, or adult onset diabetes, the most common form of the disease. Evans said the discovery was fortuitous. Researchers were looking at different aspects of the diabetic mice and did not realize they would be able to change the bone-removing activity. The assumption had been that more brittle bones in diabetics were the result of a reduced bone-building activity, not increased bone removal. "Considering the widespread use of these drugs and the known action in people it is surprising that such a key observation had been missed," he said. "The long-term use of rosiglitazone should be cautious in patients with higher risk of fractures such as older women," he added. Using it in combination with anti-osteoporosis drugs could be beneficial, he said. The research was funded by the Howard Hughes Medical Institute and the National Institutes of Health.

Avandia, mudança de bula e ameaças a médico.

O caso Avandia ainda rende: essa semana, o FDA obrigou a empresa a modificar a bula do medicamento com alerta para risco potencial de infarto do miocárdio. Hoje, The Wall Street Journal relembra das pressões sobre pesquisador de diabetes há 8 anos por causa de suas críticas ao medicamento.

Glaxo's Handling of Physician Criticized By JEANNE WHALENNovember 17, 2007 Over a period of several years, drug maker GlaxoSmithKline PLC was so concerned about a prominent physician's negative views of its diabetes drug that it engaged in a concerted effort to intimidate him and stifle his opinion, a report by the U.S. Senate Finance Committee found. The report offers a window into the rarely acknowledged practice among drug companies of monitoring and seeking to influence the opinions of leading physicians, who can make or break a drug's sales. The report alleges that Glaxo Chief Executive Jean-Pierre Garnier and former research chief Tachi Yamada were involved in the intimidation.The Senate Finance Committee released the report Thursday, after researching Glaxo's relationship with John Buse, a diabetes expert and professor of medicine at the University of North Carolina in Chapel Hill. In 1999, Dr. Buse began expressing concerns about the cardiovascular risks of Avandia, one of Glaxo's top selling drugs. The Senate Finance Committee investigated the matter because it has jurisdiction over Medicare and Medicaid and wants to ensure that they are paying for safe and effective medicines, the report says. The committee, led by Montana Democrat Max Baucus and Iowa Republican Chuck Grassley, didn't recommend any particular action. It said it feared the Avandia case was part of a "troubling pattern of behavior by pharmaceutical executives." "The effect of silencing [Dr. Buse's] criticism is, in our opinion, extremely serious," the report concludes, noting that patients may have needlessly suffered heart attacks during the period. "Had GSK considered Avandia's increased cardiovascular risk more seriously when the issue was first raised in 1999 by Dr. Buse, instead of trying to smother an independent medical opinion, some of these heart attacks may have been avoided," the report says. This week, the Food and Drug Administration forced Glaxo to add a strong new warning to Avandia's prescribing label about potential heart-attack risks for patients taking the drug. A Glaxo spokeswoman, Nancy Pekarek, said the company strongly disputes the committee's conclusions. She said Glaxo had tried to correct Dr. Buse's "inaccuracies" about Avandia but had never tried to intimidate or silence him. "People at the time were very passionate about this new medicine and could perhaps have handled the interactions with Dr. Buse better," she said. "We did apologize to Dr. Buse for the tone of some of the conversations, and he accepted that apology eight years ago." She said Dr. Garnier had no additional comment. Dr. Yamada, who is now president of the global health program at the Bill & Melinda Gates Foundation, was traveling Friday and unavailable for comment, his assistant said. In an interview last month with Nature magazine, Dr. Yamada said that he never pursued any "diabolical plot" against Dr. Buse. Dr. Buse was also traveling Friday and unavailable for comment.

Voltando ao caso Avandia: impacto para a empresa

Abaixo, notícia publicada no Valor Econômico de ontem, 24/10/2007 sobre os lucros da Glaxo Smith Kline.

Um detalhe: traduzir The New England Journal of Medicine para Jornal de Medicina de Nova Inglaterra é excesso de licença poética! The Lancet será O Bisturi? Cuidado, O Bisturi já existe há quase cem anos. Ele é o jornal do Centro Acadêmico "Oswaldo Cruz" da FMUSP.

GlaxoSmithKline registra queda de 7% em seu lucro líquido no terceiro trimestre SÃO PAULO - A farmacêutica GlaxoSmithKline (GSK) anunciou hoje uma queda de 7% em seu lucro líquido no terceiro trimestre, para 1,88 bilhão de libras, contra 2,02 bilhões de libras no mesmo intervalo do ano passado. As vendas recuaram 3% no período, para 5,48 bilhões de libras. Os motivos para as quedas no lucro e nas vendas foram a forte redução no comércio da droga anti-diabetes Avandia e a competição com medicamentos genéricos no mercado dos EUA. Além do resultado, a empresa também anunciou um programa de reestruturação para cortar 1,5 bilhão em custos no intuito de tentar compensar os problemas com genéricos e com o Avandia no ano que vem. A GlaxoSmithKline se mantém no caminho para alcançar suas metas para o ano, apesar desses desafios significativos, disse o executivo-chefe da empresa, Jean-Pierre Garnier, que deve se aposentar em 2008. As vendas da família Avandia caíram 38%, para 225 milhões de libras entre julho e setembro. Apenas nos EUA, elas recuaram 48%, para 130 milhões de libras. Nesse país, a queda foi causada pela preocupação dos usuários quanto à sua segurança, questionada por um artigo publicado em maio no Jornal de Medicina de Nova Inglaterra.

Avandia, agora o concorrente é melhor.

A saga da rosiglitazona continua em tela. Mais, uma metanálise publicada - adicionando os dados mais recentes da própria GSK - mostrou novamente aumento do risco de infarto do miocárdio, o artigo está publicado em JAMA. Esse artigo não chega a ter o impacto contra o Avandia, como esse outro publicado na mesma edição de JAMA. Trata-se de outra metanálise,mas com o concorrente, a pioglitazona, onde revela-se que esse medicamento reduz o risco de morte, infarto do miocárdio e acidente vascular cerebral.

Depois da Avandia, a GSK se reestrutura.

A crise deflagrada pela revisão sistemática do Avandia e, a defesa pífia da Glaxo Smith Kline motivou queda do valor das ações e a necessidade de recomposição do capital da empresa.

Leia no The Financial Times como a empresa está se safando das dificuldades. Porém, tenta a todo custo manter a linha OTC (over the counter) que é bem estabelecida no Reino Unido e Estados Unidos e, relativizada no restante do mundo. Aqui, temos o Behind the Counter, isto é medicamento solicitado ao balconista, mas não disponível nas prateleiras.

Aniversário do Blog

Completou um ano de idade, o Blog do Paulo Lotufo. Dirigido à elite, ele está sendo lido pela elite, sem qualquer preconceito. Jornalistas e assessores de imprensa representam um proporção generosa dos frequentadores assíduos dessas páginas.

Graças a Roberto Romano, ao blog do Alon e a revista Pesquisa Médica houve saltos no acesso a esse blogue.

O enfoque principal continuará ser a macropolítica da saúde e da educação em mundo globalizado há muito tempo.

No início enveredei um pouco no midia criticism, mas confesso que não é a minha especialidade e, trata-se de tarefa das mais difíceis. Por isso, abandonei o acompanhamento da imprensa, exceto na cobertura da violência, em particular das taxas de homicídio, que considero um dos equívocos mais sérios da cobertura jornalística brasileira.

Outro lado, que evitei foi o passionalismo da blogosfera não entrando em questões político-partidárias. Quem gosta de sangue, terá outros locais para extravasar suas frustações. Por isso, limitei várias manifestações que considerei indevidas.

As questões relacionadas a direitos humanos -enfermeiras búlgaras presas na Líbia - tiveram grande repercussão, bem como o caso Avandia que proporcionou um recorde de acessos e, segundo uma jornalista foi o local onde parte da imprensa da área se atualizou.

Por uma questão de disciplina profissional, estou dedicando meia hora do dia para editar o post do dia. Haverá sempre mais temas para comentar do que tempo para editá-los.

Avandia, o voto vencido na reunião do FDA.

Clifford Rosen, endocrinologista que dirigiu a comissão do FDA que manteve a comercialização do Avandia nos Estados Unidos foi voto vencido na reunião de 30 de julho. Hoje, no The New England Journal of Medicine ele apresenta as razões do seu voto. (clique aqui, acesso livre) O artigo é simples e de fácil compreensão por não médicos ou epidemiologistas. Em suma, o FDA considera que o importante é reduzir a glicemia, mesmo que o diabético tenha um infarto do miocárdio.

Meu mestre, Virgílio Gonçalves Pereira, um clínico fantástico, adorava afirmar que alguns médicos preferiam assinar atestado de óbito de um paciente com exames normalizados, a dar alta com exames alterados.

Virando a medicina de ponta cabeça

Se você tiver interesse em em entender como fatores de risco tornaram-se doenças e, como sintomas foram substituídos por números. O livro Prescribing by Numbers

Drugs and the Definition of Disease de Jeremy A Greene é obrigatório. Entenderá também a bizarra decisão do FDA no caso Avandia. Em outras palavras, o medicamento não reduz o risco de doença coronariana, aumenta o de insuficiência cardíaca, mas reduz o valor da glicemia no jejum. Entenderam?

FDA: comissão considera que Avandia deve continuar no mercado.

20 x 3 foi o resultado. Leia no The New York Times. Interessante, o maior problema do diabetes é aumentar o risco de doença cardiovascular, mas o Avandia, não aumenta, nem reduz o risco de doença coronariana, diz o FDA. Então, por que prescrevê-lo?

FDA avaliará Avandia na próxima semana.

Voltando ao caso Avandia. Na próxima, semana o FDA irá avaliar se o medicamento aumenta ou não o risco cardiovascular. Porém, será desconsiderado o artigo publicado no The New England Journal of Medicine porque: We should note that while Dr. Nissen’s meta-analysis … engendered considerable public notice and concern … this metaanalysis, performed out of necessity on study level data, will not be a focus of this Advisory Committee meeting. … This is because we believe the results of the analysis performed by GSK and subsequently by the FDA on the more granular individual datasets do not greatly differ from that of Dr. Nissen … Importantly, though, we believe that the FDA analysis of the data, including patient level data, is more robust than would be possible for an analysis utilizing study-level data alone.

O texto imenso com quase 500 páginas está disponível clicando aqui. Se for por motivo processual, com implicação jurídica, talvez tenha o mínimo de nexo. Porém, como não considerar estudo que até agora, apesar do imenso esforço não houve invalidação científica do método e resultado.

Steven Nissen, novamente no holofote

Se você não aguenta mais o caso Avandia descrito aqui em detalhes, passe adiante, mas se quiser recapitular clique aqui. Abaixo, mais um capítulo centrado na figura de Steven Nissen.

The New York Times descreve nesse domingo (artigo completo para registrados no site) as atividades de Steven Nissen, o pesquisador que mostrou os problemas de segurança com o Avandia. Muitos dizem que ele tem como objetivo dirigir o FDA. Apesar do rigor do artigo publicado no The New England of Journal , Nissen cometeu deslizes como afirmar que Avandia mataria mais gente do que o 11 de setembro. Questiona-se também o fato de que Nissen procura ativamente financiamento da indústria, mas sempre afirma que o dinheiro é distribuído para instituições de caridade. Nas quais se incluem entre outras, American College of Cardiology e o Cleveland Museum of Art, onde trabalha sua mulher.

Tudo isso é perfumaria e bobagem perto da afirmação que após ter sido o responsável principal pela derrubada do Vioxx, Nissen está trabalhando em ensaio clínico com o Celebrex, também um inibidor da COX-2, do mesmo grupo farmacológico do Vioxx.

Avandia: julgadores em conflito

A agência Bloomberg que informa que a comissão que analisará o caso Avandia para o FDA é composta seis médicos com conflito de interesse em relação ao medicamento, conforme o texto da agência. O mesmo problema ocorreu na análise do Vioxx e Bextra pelo FDA.

July 16 (Bloomberg) -- Six doctors with financial ties to the pharmaceutical industry, including stock holdings or speaking fees, will be among members of a U.S. advisory panel on the use of a GlaxoSmithKline Plc diabetes medicine linked to heart risks. The doctors will discuss the safety of the drug, Avandia, and similar treatments at a July 30 meeting convened by the Food and Drug Administration. As many as four of the six doctors with conflicts may vote on recommendations to the FDA, according to financial disclosure documents released by the agency. The agency wouldn't say how many members the committee will have. The FDA lets too many doctors with financial conflicts serve as advisers, lawmakers and consumer advocates say. Panelists with industry ties have backed drugs including Vioxx, the Merck & Co. painkiller that was withdrawn in 2004 after being linked to heart attacks and strokes. Legislation approved by the House last week would permit only one person with a financial conflict to vote on drug recommendations. ``They shouldn't appoint people with conflicts of interest,'' said Merrill Goozner, director of the Integrity in Science project at the Washington-based Center for Science in Public Interest, in an interview. ``The public perception of the evenhandedness of the process will be immeasurably enhanced if they appoint only people who do not have conflicts.'' To allow the doctors to participate in the Avandia review, the FDA is waiving rules that bar panelists with financial conflicts. Regulators, who routinely issue the waivers, say researchers often consult for drugmakers or have other ties and aren't swayed by those connections.

A voz do dono: entrevista com o CEO da GlaxoSmithKline

Abaixo, segue entrevista com o CEO da GlaxoSmithKline publicada hoje no The Wall Street Journal. Destaquei algumas opiniões como de que o risco da Avandia já era conhecido pela empresa - obviamente, em magnitude menor - e que há países que preferem comprar metralhadoras a vacinas.

Glaxo's GarnierIs Taking the Heat Defending Safety of Avandia Preoccupies,But Doesn't Consume, Drug Company's CEO By JEANNE WHALENJuly 9, 2007; Page B1 Jean-Pierre Garnier, chief executive of GlaxoSmithKline PLC, has been in the hot seat since May, when an article in the New England Journal of Medicine raised concerns about the safety of the diabetes treatment Avandia, his company's second-biggest selling drug. In the article, cardiologist Steven Nissen analyzed 42 past clinical trials of Avandia -- an approach known as a meta-analysis -- and concluded that patients taking the drug may be at a higher risk for heart attacks than patients taking other drugs. Since then, Avandia prescriptions have fallen sharply, and Glaxo's stock price has plummeted. Dr. Garnier is now trying to fight research with research. He says Glaxo performed its own meta-analysis of Avandia before Dr. Nissen's -- and also found a risk of heart attack. But the risk was very slight, and was outweighed by other evidence showing that Avandia is as safe for the heart as other diabetes drugs, Dr. Garnier says. The Food and Drug Administration is now carrying out its own meta-analysis and will convene a panel of medical advisers on July 30 to weigh the evidence. Dr. Garnier has faced safety crises before. In 2004, medical experts raised concerns that Glaxo's Paxil and other antidepressants could induce suicidal thinking and behavior in children, leading the FDA to add strong warnings to the drugs. In an interview in Glaxo's Philadelphia office, Dr. Garnier discussed such topics as managing the Avandia crisis, the pricing of HIV drugs, serving poor communities and what he wants to accomplish before stepping down as CEO in May 2008. Excerpts follow. WSJ: Has Glaxo done everything it could to study Avandia and communicate its risks to the public? Dr. Garnier: We're not perfect, I'm sure. With 20-20 hindsight we could have done more. But I have to say in the case of Avandia, you see that we were diligent from the day of the launch to start to study the drug in some depth in [clinical] studies and then we did the meta-analysis a year ahead of Dr. Nissen. As soon as we found out that there was at least a question raised by the meta-analysis, we immediately did the epidemiology study with 30,000 patients that came out absolutely squeaky clean and supportive of Avandia. So you look at the totality, Avandia is by far the most studied diabetic agent on the market today. So sure, maybe we could do more, but frankly the record is very good. Not only have we studied this drug right, left and center, but also we have been transparent, informed everybody. WSJ: What feedback are you getting from doctors about Avandia? Dr. Garnier: Doctors are worried about being sued for putting patients on Avandia and things like this. But overall, they are staying behind Avandia. Very few patients actually are switching off their medication. But some have. WSJ: Are doctors more concerned about liability risk when putting new patients on the drug? Dr. Garnier: Physicians are naturally gun-shy about putting new patients on. The reality is, and we have the data, they're putting fewer new patients on it. We've just run a big survey of physicians, and they're playing back again the two key points: "Most of my patients have not switched, and I have no intention of switching them. However, as far as putting new patients on Avandia, I'm putting far fewer than before, and I'm waiting to see what the FDA has to say." WSJ: Does the safety flap take up your entire day? Dr. Garnier: Pretty much, 24-7. This is a very unpleasant event. But on the other hand this is not my first one. I've been there before. My job is to manage the company through the crisis. WSJ: How do you do that? Dr. Garnier: We have crisis-management phone calls every day. These things don't get done without a lot of coordination. WSJ: Glaxo recently donated 50 million pandemic flu vaccines to the World Heath Organization. What's the story? Dr. Garnier: It's probably the largest vaccine donation ever. The company could have sold possibly those 50 million units. They [Glaxo] decided to set them aside because frankly those countries are not going to buy any pandemic vaccine. Some of them have no commitment to health care. Let's call a cat a cat. They'll buy a lot of other things including Kalashnikovs before they allocate enough money for health care in their own countries. [Some] are committed to better health care but [pandemic flu] never makes their top 10 list because they have humongous problems. They have HIV, and they have this and that. So putting resources aside for a maybe problem doesn't work out to their top priority. WSJ: How has Glaxo changed its HIV-drug pricing in the developing world since you started running the company? Dr. Garnier: I always wanted to have access as part of the DNA of the company. I don't look at those things as philanthropic undertakings. Even Tykerb -- we just introduced this breast-cancer treatment in the U.S. It's a very expensive product for the average person. We provide funding and subsidies for people up to an income level of $100,000 per family. It's intertwined with the purely commercial pricing. I wanted that. I never wanted to just close my eyes to the fact that 80% of the population won't be able to afford the drugs. Because that's the truth -- 80% of the market for pharmaceuticals comes from 20% of the world-wide population. I'm not going to be CEO of a company that just works for rich countries. And even within rich countries, by the way, you have holes in the safety net that are part of the equation. WSJ: What has that meant in HIV? Dr. Garnier: To me, it became very obvious that we had to go much further than to give discounts [on drugs]. We had to make basically a philosophical statement that for the very poor countries of this world, we were going to sell our drugs without making a profit, completely not for profit. And overnight we did this. And that allowed the consumption of HIV drugs in Africa to increase dramatically, exponentially. Overnight we went from very little to hundreds and hundreds of millions of tablets. Then we went one step further and said, why don't we give licenses to generic companies [to make our drugs], particularly local companies. Maybe they can make it even cheaper. WSJ: What are the main things Glaxo has done to provide better access [to HIV drugs] and what's been the effect? Dr. Garnier: What we sell at this not-for-profit price corresponds to roughly a million patients being treated, mostly in Africa. We dropped the price, helped with access -- that is, we have a number of community support programs. Because treating people who have HIV is not a simple thing. WSJ: What are you doing? Opening clinics? Hiring doctors? Dr. Garnier: No, we don't own the infrastructure but we've supported clinics. Not just with money -- with advice, sending doctors. WSJ: Do you do much licensing for production of your drugs in middle-income countries like Thailand? Dr. Garnier: No, no, no. Middle-income countries should pay a fair price for our drugs. They certainly can use some of their resources to pay a fair price, which is clearly an intermediate price between the lowest and the highest -- we try to price according to standard of living. WSJ: You're retiring next year. What more do you want to do? Dr. Garnier: No. 1 is deliver the pipeline. We have a very exciting, high-quality, deep, dense, innovative pipeline of late-stage drugs. So let's make sure we deliver, and those drugs pass the last hurdle and get launched.

Ah, esse monstro de olhos verdes..

Heartwire, o boletim do InfoHeart apresenta os problemas do foco na pessoa de Steven Nissen e, não no FDA e na Glaxo-Smith Kline no caso Avandia. O título acima é uma tradução tosca de Otello de Shakespeare, que os americanos popularizam como The Irish eyes of envy. Sim, a inveja é a aquilo que os caminhoneiros escrevem nos para-choques.

The media, the man, and his message: Nissen seeks to refocus scrutiny on rosiglitazone June 21, 2007Shelley Wood New York, NY - The first act appears to be over in the rosiglitazone (Avandia, GlaxoSmithKline) drama, but the media have not yet loosened their grip on the man who first sounded the alarm about the diabetes drug: Dr Steven Nissen (Cleveland Clinic, OH). Nissen's meta-analysis, published in the New England Journal of Medicine (NEJM) and reported by heartwire, propelled rosiglitazone into the spotlight, culminating in a congressional hearing earlier this month and an FDA hearing on July 30. Despite Nissen's repeated insistence that the focus should be on patient safety, not his methods or motives, newspapers and their editorialists—as well as alternative media—continue to take disparate views on the man in the middle of the maelstrom. Dr Steven Nissen An editorial in the Cleveland Plain Dealer insists Nissen is being victimized for championing the public good . "Nissen, and clinicians like him around the country, aren't sifting drug performance data so they can add to their scrapbooks of news clippings. They're doing it so they can add to the store of knowledge in the medical community, which can then improve care for patients," the Dealer asserts. "As it now stands, public-spirited doctors like Nissen, who are trying to save patients grief, can be accused of poking their noses where they don't belong. That's ludicrous." Other media outlets have profiled Nissen, emphasizing his lifelong activism in different spheres. A glowing portrait of Nissen on MedPageToday.com points out that he was a part of the college antiwar movement during the 1960s at the University of Michigan. "His years as a campus activist left him with an entrenched commitment to righting wrongs and a willingness to challenge the status quo, attributes that he has integrated into his medical career," Peggy Peck writes for MedPageToday. "And he never forgot the power of the press." Altruism not universally accepted Indeed, the mainstream media loves a whistleblower, but not all of the coverage of Nissen's role has accepted the notion of him as altruist. Earlier this week, the Wall Street Journal (WSJ) ran an editorial questioning the "larger political context" in which the rosiglitazone concerns were raised, noting that "Dr Nissen has a reputation as an adversary of the pharmaceutical industry" and that he "admitted that he consulted with several congressional committees" prior to the publication of his rosiglitazone meta-analysis. "Ostensibly serious medical research isn't supposed to be peer-reviewed by the Democratic majority," the WSJ editorial gibes. Nissen, for his part, has repeatedly rejected claims that politics had anything to do with it. "That's just not what happened," he told heartwire. "The scientific process proceeded in the usual way: the journal had the article reviewed by peer scientists, it was a very careful review, it was revised based upon those reviews, and it has absolutely nothing to do with politics, it was about patients. . . . If the reviewers had not recommended publication, I'm sure that the NEJM would not have published it." Other news coverage has implied that Nissen had a different, more personal, political agenda. On June 5, Boston Globe staff reporter Diedtra Henderson quotes critics who claim Nissen's motives stem from a desire to run the FDA, a charge Nissen flatly rejects. "I'm not running for anything," Nissen is quoted in the Globe. "I've got a great job here [at the Cleveland Clinic], and I'm not going anywhere." Nissen reiterated this point to heartwire: "Speculation about the FDA is a very common topic. I am very happy as the chair of CV medicine at the Cleveland Clinic: I have no interest in going anywhere else; I have my hands full. I'm certainly not interested in running for an office like the FDA commissioner, I don't know where that comes from, it certainly doesn't come from me." Headline news A sticking point for the media mania around Nissen has been his apparent eagerness to make headlines. That was also the charge levied by California Republican Rep Darrell Issa during the congressional hearing, where he accused Nissen of caring more for making a "public splash" in the media than informing the FDA directly of his concerns about rosiglitazone. Even earlier, a Bloomberg news report posted online when his meta-analysis was first published notes that Nissen "put the Cleveland Clinic's in-house television studio to good use this week, appearing on a dozen broadcasts across the world." Nissen agrees that his paper "had more than the usual amount of media attention," but, he insists, "We published this because of the science. It was certainly not about politics, it's certainly not about media. . . . Ninety-nine percent of the coverage of the rosiglitazone story has been very good and very responsible. It's a very tiny group that's making an effort here to make this about the messenger, not the message." Nontraditional media have their say The bulk of that negative press has come from independent bloggers and other nontraditional media, many with major conflicts of their own. One of the more novel was a video podcast on the popular video-sharing website, YouTube, that opens with the question, "What do you think about a doctor … who compares a diabetes drug to 9/11?" a reference to a comment Nissen made during an interview that aired on ABC's Nightline website. The one and a half minute video features Dr Michael Weber (SUNY, Brooklyn, NY) expressing his misgivings about how Nissen described rosiglitazone's risks in the media. But the YouTube video was funded by the Center for Medicine in the Public Interest (CMPI), a "research" organization funded by the pharmaceutical industry, and Weber's own ties to industry have been scrutinized in the past. Contacted by heartwire, Weber said he did not even know what YouTube was. He stated that he is a member of an external, unpaid advisory group of directors for the CMPI and that the CMPI approached him to do "a video," not the other way around. He also emphasized that his comments were not about the scientific validity of the study, but about how they were disseminated. "As far as I'm concerned, the full story about Avandia still isn't known, and the concerns that were raised by Dr Nissen may be something we need to find out about," Weber said. "I'm not criticizing or disputing the scientific data, and in fact the whole reason I agreed to be videoed was because I did get very upset when I saw that Steve had said that the Avandia situation was worse than what happened on 9/11. I found that to be the sort of hyperbole that is really unacceptable in discussing these sorts of issues, and as a New Yorker, the statement was particularly unacceptable." But Weber rejected any suggestions that he himself was conflicted in this particular circumstance. "I do consult for industry, and I have done research projects and been a part of research activities that have been funded by industry, and I've always fully disclosed or acknowledged those. In this case, there is really not an industry connection, because I have not in any way defended Avandia or defended the way the company that manufactures Avandia has managed the situation." Nissen says he hasn't seen the video and doesn't want to. "What can I say? We publish scientific work, we did this analysis not to address the YouTube audience but because we believe that providers and patients have a right to know that there are significant safety issues with rosiglitazone," he told heartwire. "If it in fact stimulates people to create YouTube videos, I can't do anything about that, but that's not the audience." Blogs and missed potential Other blogs, associated with online editions of newspapers and magazines, have also debated Nissen's role. Ivan Oransky, blogger for The Scientist online, pointed out that Nissen has twice in the past year been wrong about drugs that he thought "held promise": torcetrapib (Pfizer), and now rimonabant (Sanofi-Aventis), the latter unanimously panned by the FDA's advisory panel last week. Oransky's observations were subsequently picked up in the WSJ health blog by veteran reporter Scott Hensley, who observed that Nissen, "a frequent and outspoken critic of the drug industry," has an "imperfect crystal ball." Oransky, quoted by Hensley, writes: "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." This is not like handicapping horse races; it's about doing good scientific studies and reporting the results in a faithful and accurate fashion. Nissen calls this a "straw-man" argument. "I'm always enthusiastic about drugs that we're studying, but when results come in, we tell it the way it is," he told heartwire. "I don't predict the success of drugs, I study the effects of drugs. . . . I have no vested interest, personally, one way or another in whether a drug works or not. It's my job to report scientific results in a neutral fashion, and I never predicted that torcetrapib would be successful. I thought it had great potential, and that was a potential that didn't pan out." In the case of rimonabant, investigators, including Nissen, did not have data on psychiatric side effects of the drug. "I'm glad that those data were reviewed; I hope that it can be overcome, because I do think [rimonabant] has potential. But this is not like handicapping horse races; it's about doing good scientific studies and reporting the results in a faithful and accurate fashion." Biting the hand that leads For health reporters, Nissen is a rare gem in the parched, baked earth that is the medical/pharmaceutical beat. In a sphere where wooden interviews, cautious opinions, and technical jargon are the norm, Nissen speaks his mind and is deliciously quotable. At the major cardiology meetings when he's spoken at a press conference, Nissen will glide through the pressroom like he's hosting a garden party, offering opinions, warmly greeting reporters by name. Asked whether the proximity he's always enjoyed, even nurtured, with the press has come back to bite him, Nissen cordially steers the conversation back to where he insists it should remain. "The last thing in the world I want is for this to be about me. It has to be about the science. If there are criticisms of the manuscript, let them be directed at the science, not at the messenger." Yet even as the hue and cry dies down, many journalists following the rosiglitazone saga are left wondering if Nissen—always so frank with and accessible to the media—may, this time, have gotten more attention than he wanted. Which just goes to prove the adage: Be careful what you wish for, you just might get it.

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.