sexta-feira, 22 de agosto de 2008

ELSA no ano 1 saúda os 60 anos do "vovô" Framingham Heart Study

Em breve, o Framingham Heart Study completará 60 anos. Esse estudo iniciado em 1948 com mais de 5 mil pessoas na cidade do mesmo nome, próxima a Boston representa um dos grandes legados da epidemiologia à ciência e saúde pública. Impossível falar em fatores de risco cardiovascular sem os resultados de Framingham.
Essa semana, os quatros primeiros participantes terminaram os exames iniciais do Estudo Longitudinal de Saúde do Adulto, na sede paulista do projeto localizado no Hospital Universitário da USP. Na foto, a coordenadora, professora Isabela Benseñor e técnica Angelita trocam a placa no primeiro dia do estudo. O ELSA examinará 15 mil pessoas em SamPa (5 mil), BH (3 mil), Salvador (2 mil), Rio (2mil), PoA (2mil) e, Vitória (1 mil). Trará informações sobre os determinates do diabetes e da doença cardiovascular em uma população brasileira. Trata-se do grande empreendimento dos epidemiologistas brasileiros que aproveitam o momento para saudar o aniversário do "vovô" Framingham.

Vacina para o HPV: custo-benefício discutível

O PharmaBlog faz um resumo abaixo muito bom do artigo sobre a custo-efetividade da vacina para o HPV. Esse é recidivante nesse blogue, basta clicar aqui para ver o debate nos Estados Unidos a conduta do nosso Ministério da Saúde.
Eu volto a repetir o post de 19/01/07: "... quem precisará da vacina, não terá acesso e, fará uso quem tem risco mínimo de câncer de colo uterino. É o fenômeno descrito na Inglaterra por Julian Tudor- Hart chamado "inverse care law". O Ministério da Saúde precisa ser rigoroso e, impedir a liberalização total de venda da vacina? Sim, porque (1) somente o Ministério poderá comprar a vacina e, quem tomar em clínica particulares irá deduzir o valor pago no imposto de renda. Ou seja, por compra direta ou por renúncia fiscal, a conta será do erário; (2) existirá em breve, alternativa da Glaxo, que poderá ser mais barata e efetiva. Por isso, se o Ministério facilitar a venda do produto da Merck estará "matando" o concorrente que poderá ser ou não a melhor opção (não há dados confiáveis) entre as duas estratégias de prevenção. No entanto, a prioridade de aplicação em termos de faixa etária, região e categoria social deveria ser do Ministério. Porque, se com certeza, a moça de 15 anos moradora em Brasília Teimosa em Recife se beneficiará mais da vacina, do que a senhora de 35 anos moradora no plano piloto de Brasília, não preciso ser advinho para saber quem terá e, quem não terá acesso à vacina, casos as "leis de mercado" prevaleçam."
Pharma Blog » 2008 » August » 21 Gardasil Isn’t Worth The Cost For Women Over 18 By Ed Silverman // August 21st, 2008 // 8:05 am That’s the conclusion of a new study that is going to make life much harder for Merck to wring needed sales out of its controversial HPV vaccine. The study, which appears in the New England Journal of Medicine, comes as the drugmaker is already struggling to convince college-age and older women to get the vaccine, which costs about $360 for a three-dose regimen. The vaccine, which is approved for girls and young women ages 9 to 26, makes economic sense for preteens because they are less likely to have the sexually transmitted virus that causes cervical cancer, according to the study. But the cost-benefit depends on how long Gardasil’s protection will last, although Merck contends the vaccine is cost effective for women through age 24. The analysis predicted that life expectancy gained by giving Gardasil to women older than 18 doesn’t outweigh the expense. “We aren’t saying older women can’t benefit. We are just saying that from a societal perspective there might be a better use of this investment in money,” Jane Kim, an author on the study and an assistant professor of health decision science at Harvard University, tells Bloomberg News. “You are getting diminishing returns.” The researchers compared the price of the vaccine and other expenses involved in getting the shot along with regular pap smears to the cost of pap smears. A pap smear, which detects abnormal cell change that could signify cervical cancer, costs about $38.68 and is recommended at least once every three years for women ages 21 through 64, according to the National Institutes of Health. To wit, Gardasil cost about $43,600 per “quality-adjusted life year” gained when administered to 12- year-old girls. This falls below the $50,000 per QALY benchmark used by many researchers as a maximum for cost-effectiveness, although other researchers cite $100,000 per QALY. It would cost $97,300 per QALY, however, to vaccinate girls and women through age 18; $120,400 per QALY for girls and women up to age 21, and $152,700 for girls and women up to age 26. However, the cost becomes more attractive when considering protection against genital warts - the cost per QALY when given to 12-year-olds falls 20 precent to $34,900, and to $133,600 for a program through age 26. Current data has only looked at Gardasil’s ability to stop HPV for up to five years. It is unknown whether Gardasil can reduce overall rates of cervical cancer and deaths, Charlotte Haug, editor-in-chief of the Journal of the Norwegian Medical Association, wrote in a separate editorial also published in the New England Journal. “There is good reason to be cautious about introducing large-scale vaccination programs,” Haug tells Bloomberg. “Instead, we should concentrate on finding more solid answers through research rather than base consequential and costly decisions on yet unproven assumptions.” It is routine for vaccines to be used after five years of efficacy data and it would be unfair to patients keep the product off the market while researchers study its long-term effects, Rick Haupt, Merck’s executive director of Gardasil clinical research, tells Bloomberg. Merck may present data this year on the effects of the vaccine over nine years. Gardasil protects against the HPV strains 16 and 18, which are responsible for 70 percent of cervical cancers, and HPV strains 6 and 11, which cause 90 percent of genital warts. While many of the sexually transmitted infections caused by HPV are resolved naturally, others develop into genital warts and cervical cancer. The CDC recommends girls be vaccinated at age 11 or 12.

segunda-feira, 18 de agosto de 2008

Caso Vioxx: ver o post anterior. Aqui, o editorial do The Annals of Internal Medicine

Seeding Trials: Just Say "No" Harold C. Sox, MD, Editor, and Drummond Rennie, MD Annals of Internal Medicine 19 August 2008 Volume 149 Issue 4 Pages 279-80 The public has lacked convincing documentary evidence of a long-suspected drug company practice: promoting a new drug by sponsoring a randomized trial in which participating physicians use the drug as they follow the trial protocol. This practice—a seeding trial—is marketing in the guise of science. The apparent purpose is to test a hypothesis. The true purpose is to get physicians in the habit of prescribing a new drug. Why would a drug company go to the expense and bother of conducting a trial involving hundreds of practitioners—each recruiting a few patients—when a study based at a few large medical centers could accomplish the same scientific purposes much more efficiently? The main point of the seeding trial is not to get high-quality scientific information: It is to change the prescribing habits of large numbers of physicians. A secondary purpose is to transform physicians into advocates for the sponsor's drug. The company flatters a physician by selecting him because he is "an opinion leader" and incorporates him in the research team with the title of "investigator." Then, it pays him good money: a consulting fee to advise the company on the drug's use and another fee for each patient he enrolls. The physician becomes invested in the drug's future and praises its good features to patients and colleagues. Unwittingly, the physician joins the sponsor's marketing team. Why do companies pursue this expensive tactic? Because it works (1, 2). It works, but it may endanger the unwary physician. The tide is turning against the physician who accepts emoluments from drug companies. Academic institutions and professional organizations are issuing ethical guidelines that proscribe transactions in which drug companies pay physicians an amount that is disproportionate to the services that the physician provides (3, 4). The office of the U.S. Inspector General has issued guidance about which transactions are legal. Although its guidance focuses on gifts, it also states that payments for participation in research "should be fair market values for legitimate, reasonable, and necessary services" (5). Moreover—and most ominously for the future of seeding trials—"postmarketing research activities should be especially scrutinized to ensure that they are legitimate and not simply a pretext to generate prescriptions of a drug" (5). Several years ago, Annals published a seeding trial (6). Merck & Co. (Whitehouse Station, New Jersey) sponsored ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness), a large, community-based, randomized comparison of a cyclooxygenase-2 inhibitor (Vioxx [rofecoxib]) and a nonselective cyclooxygenase inhibitor (naproxen). At the end of the 3-month follow-up, the proportion of patients who discontinued naproxen was larger (8.1% vs. 5.9%) than that of those who discontinued Vioxx. We published the study because we thought that physicians would be interested in the low discontinuation rates for both drugs and the small difference between them. No one told Annals the true purpose of ADVANTAGE. We learned about it when we received a letter to the editor from Dr. David Egilman, who was a consultant to the plaintiffs' attorneys in the civil suits against Merck (7). He had access to publicly accessible trial documents, which included Merck employees' e-mail messages that disclosed the true intent of the ADVANTAGE trial. These messages are the meat of the article about seeding trials published in this issue by Hill and colleagues (8). To our knowledge, this article is the first to provide documentary evidence that proves the existence of seeding trials. Other than an excerpt from a single industry document cited in an article by Kessler and colleagues (9), we have not had "smoking gun" evidence, in which the perpetrators are on public record about why they conducted a trial like ADVANTAGE. The article provides clear evidence that the intent of ADVANTAGE was to increase prescriptions of Vioxx (the study outcome of greatest interest to Merck seems to have been Vioxx prescribing rates). However, despite the large body of documents searched by the authors, they discovered few details about exactly how Merck's marketing division carried out ADVANTAGE. The documents do tell us that deception is the key to a successful seeding trial. That information—once it becomes general knowledge—could be the fatal blow for seeding trials. Institutional review boards, whose purpose is to protect humans who participate in research, would probably not likely approve an action that places patients in harms' way in order to influence physicians' prescribing habits. If they knew, few established clinical researchers would participate as coinvestigators. Few physicians would knowingly enroll their patients in a study that placed them at risk in order to provide a company with a marketing advantage, and few patients would agree to participate. Seeding trials can occur only because the company does not disclose their true purpose to anyone who could say "no." It is also true that seeding trials exist only because physicians say "yes" to a deal that seems too good to be true. Academic physicians agree to be on the byline of an article that someone else wrote about a study that someone else designed and paid for because there is considerable prestige, little effort, and low risk (10). A practicing physician says, "Why not?" when he learns that he has been selected to participate in an important clinical trial and receives inducements designed to make it an offer he will not refuse. Our parents prepared us for this moment when they warned us to ask questions when someone offers us easy money. We owe it to them and especially our patients to ask if we are being recruited to participate in a seeding trial. How can people with decisional responsibility—institutional review boards, researchers, physicians, and patients—identify a seeding trial? They could ask the about the intent of the trial. If the answer was "It's a seeding trial," most would say no, and seeding trials would soon fade away; but this scenario is a fairy tale, because sponsors would probably ascribe a scientific purpose to the trial and proving otherwise would be difficult. Nonetheless, institutional review boards could routinely ask, "Is this a seeding trial?" Sponsors would think twice about lying to an institutional review board, an institution that has so much legal and public support, especially in an era in which e-mail messages seem to live on forever, awaiting discovery by a curious someone. Asking about intent may be the wrong approach. Does the goodness of a trial inhere in its intent or in something else? An adequately powered trial is good if it tries to answer an important scientific question on which patients should be in equipoise, even though participating physicians will become familiar with a new drug and be more likely to prescribe it. Is the same trial bad if its main purpose is to increase drug sales by habituating trial physicians to prescribing a new drug? Couldn't the answer to this question depend on the scientific importance of the question that it addresses? The trial would be bad if it addressed a question that lacked merit but good, despite its intent, if the question had intrinsic merit. Does the motivation for the trial make it wrong to participate in it, or does addressing an important, unsettled question make the study worthwhile, despite its intent? Perhaps physicians should focus less on intent and more on the scientific question. The ADVANTAGE physicians should have been asking whether the trial addressed an issue that previous trials had already answered—or should have answered. This line of reasoning suggests that institutional review boards, researchers, physicians, and patients should be asking about the study hypothesis and whether it addresses a settled question. Physicians have a fiduciary obligation to ask these questions on behalf of their patients, as do institutional review boards and researchers, which have the skill set and personnel to judge whether a trial is asking an already-answered question. They could look for other clues, such as a study with an open-label design, no control group, a very large projected enrollment relative to the importance of the question, a short-term study of a chronic disease, a study of an already approved drug, and so forth (1, 8, 9). None of these clues is highly specific, but institutional review boards should start asking questions when a study has several of them. A bureaucratic solution, such as relying on institutional review boards, could help to rid us of seeding trials, but simply shining a bright light on their existence may have already sown the seeds of their destruction. The next step would be a societal consensus that it is wrong to deceive institutional review boards and participants about the true purpose of a trial. Therein lies the importance of Hill and colleagues' article (8).

Por dentro do caso Vioxx

The ADVANTAGE Seeding Trial: A Review of Internal Documents
Kevin P. Hill, MD, MHS; Joseph S. Ross, MD, MHS; David S. Egilman, MD, MPH; and Harlan M. Krumholz, MD, SM Annals of Internal Medicine 19 August 2008 Volume 149 Issue 4 Pages 251-8 Background: Seeding trials, clinical studies conducted by pharmaceutical companies that are designed to seem as if they answer a scientific question but primarily fulfill marketing objectives, have not been described in detail. Purpose: To describe a known seeding trial, ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness), through documents of the trial sponsor, Merck & Co. (Whitehouse Station, New Jersey). Data Sources: Merck internal and external correspondence, reports, and presentations elicited to inform legal proceedings of Cona v Merck and Co., Inc., and McDarby v Merck and Co., Inc. The documents were created between 1998 and 2006. Data Extraction: An iterative case-study process of review, discussion, and re-review of documents to identify themes relevant to the design and conduct of ADVANTAGE. To supplement the case-study review, the authors did a systematic review of the literature to identify published manuscripts focused on seeding trials and their conduct. Data Synthesis: Review of the documents revealed 3 key themes: The trial was designed by Merck's marketing division to fulfill a marketing objective; Merck's marketing division handled both the scientific and the marketing data, including collection, analysis, and dissemination; and Merck hid the marketing nature of the trial from participants, physician investigators, and institutional review board members. Although the systematic review of the literature identified 6 articles that focused on the practice of seeding trials, none provided documentary evidence of their existence or conduct. Limitations: The legal documents in these cases provide useful, but limited, information about the practices of the pharmaceutical industry. This description of 1 company's actions is incomplete and may have limited generalizability. Conclusion: Documentary evidence shows that ADVANTAGE is an example of marketing framed as science. The documents indicate that ADVANTAGE was a seeding trial developed by Merck's marketing division to promote prescription of Vioxx (rofecoxib) when it became available on the market in 1999

Começa o maior estudo epidemiológico em doenças cardiovasculares e diabetes do hemisfério sul

Hoje, às 12:15, no Hospital Universitário da USP, a primeira participante do Estudo Longitudinal de Saúde do Adulto completou o questionários e os diversos exames do maior estudo epidemiológico em doenças crônicas do hemisfério sul. Restam 14 999 pessoas entre 35-74 anos, funcionários das universidades federais da Bahia, Espírito Santo, Minas Gerais, Rio Grande do Sul, da FIOCRUZ-Rio de Janeiro e, da USP. O financiamento é do Ministério da Saúde e do Ministério de Ciência e Tecnologia.
Maiores informações com a coordenadora do Elsa-SP, profa Isabela Bensenor, em