A closer look at the scientific validation of safety and efficacy of Tamiflu.
Jefferson T, Jones M, Doshi P, Del Mar C. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ. 2009;339:b5106.
Systemic review and meta-analysis
This review and meta-analysis is an update of the 2005 Cochrane Review on neuraminidase inhibitors. It concluded that these drugs are of modest benefit in relieving symptoms of influenza. The drugs are not effective post-exposure to laboratory confirmed influenza, and they are not proven to lessen complications of influenza such as lower respiratory tract complications.
Neuraminidase inhibitors comprise nebulised zanamivir (Relenza; Glaxo Wellcome) and oral oseltamivir (Tamiflu; Gilead Sciences and F Hoffmann-La Roche). Inhibiting neuraminidase—which, as with haemagglutin, is specific to influenza—blocks the exit of the influenza virus from the host cell, thereby preventing replication in other than a few host cells. The use of neuraminidase inhibitors, specifically Tamiflu, has increased dramatically with the spread of the influenza A/H1N1 pandemic that began in April 2009. However, the benefits of Tamiflu are yet to be determined for this application and existing evidence does not support a plausible effect on controlling the spread, reducing the severity, or preventing the complications of H1N1. Keep in mind that the FDA requires Roche to print the following disclaimer on Tamiflu labels:
Tamiflu has not been proven to have a positive impact on the potential consequences (such as hospitalizations, mortality, or economic impact) of seasonal, avian, or pandemic influenza.
Although more than 3 billion dollars have been spent on stockpiling and using Tamiflu in the face of pandemic influenza, it seems that public health officials acted despite the lack of scientific validation of safety and efficacy of Tamiflu. The same is true for many physicians.
Detailed analysis has also shown that most physicians do not make decisions of what drug to use on the basis of scientific research or cost; they base their decisions almost entirely the effectiveness of the drug companies’ marketing and advertising efforts. And, even if they are relying on journal articles for their information, they are not necessarily getting the truth. In my latest book, What the Drug Companies Won’t Tell You and Your Doctor Doesn’t Know, I provide a very detailed account of the issues. Here is what key people at the major journals have to say about the drug companies and their own journals.
- According Richard Smith, for 25 years the editor of the British Medical Journal, “Major medical journals are just an extension of the marketing departments of major drug companies.”1
- Richard Horton, editor of the Lancet, states, “Journals have devolved into information-laundering operations for the pharmaceutical industry.”2
- Marcia Angell, for 20 years the editor of the New England Journal of Medicine, comments that the drug industry is “primarily a marketing machine” that is intent on co-opting “every institution that might stand in its way.”3
- From JAMA: It is estimated that 95% of medical studies in the most prestigious journals contain false or misleading statistics.4
The current situation with Tamiflu once again highlights one of the key problems with medical research: It is funded primarily by drug companies who have a vested interest in the outcomes
The current situation with Tamiflu once again highlights one of the key problems with medical research: It is funded primarily by drug companies who have a vested interest in the outcomes. Here are a couple of pertinent points to the Tamiflu discussion:
- More than 90% of the clinical research done on drugs in the United States is funded by drug companies and conducted by clinical research organizations (CROs) who obviously try to produce data that the drug company will be pleased with.5
- Research conducted by CROs on behalf of a drug company is owned by that drug company and they control how it is interpreted, manipulated, and disclosed.6
- The overwhelming majority of research studies in medical journals are drug-sponsored and written by “ghost authors.” In one analysis, ghost authorship occurred in 40 of 44 articles (91 percent), and in 31 trials the ghost author identified was a statistician.7
- Two former employees of Adis International, a large communications company, have come forward with documents showing they had ghostwritten some of the published studies of Tamiflu with specific instructions from Roche’s marketing department.8
Roche, the manufacturer of Tamiflu, claims that its drug reduces hospital admissions by 61% in patients who were otherwise healthy before they got the flu. It has also said that Tamiflu reduces such complications as bronchitis, pneumonia, and sinusitis by 67%, and lower respiratory tract infections requiring antibiotics by 55%. A 2006 Cochrane review of Tamiflu came to similar conclusions—based largely on a review paper that looked at 10 studies, all of them funded by Roche, but only 2 of these were ever published and those 2 showed the drug had very little effect on complications compared to a placebo.
What the updated Cochrane review found was that it turns out that no credible evaluation of the data from these Roche-sponsored studies has ever occurred. Even the data from the 2 published studies has been called into question. When the Cochrane reviewers went to the lead authors of the 2 published studies, one author said he had lost track of the data when he moved offices and the files appeared to have been discarded. The other said he’d never actually seen the data himself, and directed the Cochrane team to go directly to the company.9 The bottom line is that the Cochrane researchers never received the full research documents from Roche. This situation led to chastising of Roche in various editorials and articles.10 As a result, Roche has released some documents, but hardly the full disclosure to enable proper evaluation.
One of the Cochrane reviewers concluded that the research on neuraminidase inhibitors is “fragmented, inconsistent, and contradictory,” leading to speculation that these drugs may have no “therapeutic and public health policy advantage.”9 Yet, despite all the questions on the safety (yes, there are some safety concerns as well) and efficacy of Tamiflu, the Centers for Disease Control and Prevention strongly recommends the use of Tamiflu in anyone even suspected of having the flu, possibly to justify the expenditure, and now seems unwilling to conduct unbiased research to validate Roche’s marketing claims. Perhaps they are afraid that it will be discovered that the emperor has no clothes—that Tamiflu is nothing more than another failed promise from the pharmaceutical industry. Hopefully, the outcry from the scientific community will lead to not only the proper evaluation of Tamiflu, but also the blueprint for unbiased research with full disclosure for other drugs before they become so enthusiastically anointed without proper evaluation.