What should we make of dinosaur publishers leading the charge against dangerous drugs?
On Monday, GlaxoSmithKline received some bad news about Avandia, its drug for diabetes patients. According to a study in the New England Journal of Medicine, Avandia – Rosiglitazone Maleate – increases the risk of heart attack.
Here’s the report, although readers without medical training may find it impenetrable:
- Stephen E. Nissen & Kathy Wolski. Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. New England Journal of Medicine (2007 May 21).
For a measure of the confusion that results from this type of disclosure, see Dr. Charles’ coverage at Unanswered Questions About Avandia & More on Avandia. [Update: see also this Washington Post article, presented as a FAQ.]
This may remind readers of the medical, financial and legal panic following indications that Cox-2 Inhibitors prescribed to arthritis sufferers had serious side effects. The most popular of the Cox-2 drugs were Celebrex (sold by Pfizer) and Vioxx (sold by Merck). Responding to panicking patients, doctors, regulators, and investors, the FDA and Health Canada were quick to issue warnings.
The Vioxx scandal was a natural result of a general failure to regulate drug safety, and there were widespread calls for closer and more reliable monitoring – both before and after their approval for sale by government agencies. The targets for regulatory reform don’t tax common-sense:
- the merits of post-market surveillance, including provisional licensing.
- the dangers of early pre-market licensing, and
- the unhealthy demand created for untried prescription medications by direct-to-consumer advertising.
An editorial from the journal of the Canadian Medical Association nicely summed up the problem, and advocated a sweeping regulatory solution:
The FDA and Health Canada have demonstrated their structural inability to do ongoing safety monitoring of new drugs and devices, and industry is far too conflicted to be able to carry out this important task. We need new national agencies to monitor drug safety independently from the approvals process. Only then can physicians and patients be assured an unbiased safety assessment of the drugs they are prescribing and taking.
- Vioxx: lessons for Health Canada and the FDA. CMAJ January 4, 2005; 172 (1).
Two years later, and very little has changed at either agency. Despite tentative forays in the US Congress, and ‘critical path‘ talks at the FDA, no legislation has been passed which would respond to the problem. In Canada, discussions about progressive licensing have yet to assume regulatory force, and there are indications the situation will become worse, not better.
The most significant development has come from member journals of the International Committee of Medical Journal Editors (ICMJE), who issued a statement declaring they will only publish trials previously registered with ClinicalTrials.gov, a database hosted by the National Institutes of Health.
- DeAngelis CD, Drazen JM, Frizelle FA, Haug C, Hoey J, et al. (2004) Clinical trial registration: A statement from the International Committee of Medical Journal Editors. Ann Intern Med. 141:477-8.
Soon after, the ICMJE adopted recommendations of the World Health Organization, in part to counter Big Pharma’s attempts to circumvent their requirements.
- De Angelis CD, Drazen JM, Frizelle FA, Haug C, Hoey J, et al. (2005) Is this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors. Ann Intern Med 143:146–148.
This is a story with enough alarm and money involved that it has gained significant attention. But unlike the Vioxx ‘fallout’ story in 2004, this story is made new by an extra twist. Major newspapers are framing it as a triumph for open access to information.
- Open-Source Drug Safety? – Forbes
- Glaxo Gets Googled, Avandia Data Pop Up – Wall Street Journal’s Health Blog
- For Drug Makers, a Downside to Full Disclosure – New York Times
Each of these focus on how Nissen and Wolski used information culled from GlaxoSmithKline’s own public database, the Clinical Trial Register.
This story works. It has a personalized David and Goliath theme that invites schadenfreude when a large drug company is caught by its own data.
I worry, though, that this will create confidence in informal drug monitoring that relies on whistle-blowing by objective and motivated researchers and medical journals.
It’s already happening.
Joe Weisenthal at Techdirt, floats the idea that medical journals could replace the FDA.
Looking down the road, one could envision a system whereby it’s the FDA’s job to ensure that drug companies properly report safety and efficacy data, while third parties (think highly specialized versions of Consumer Reports) make judgments on a drug. Then, instead of having blanket pronouncements on whether a drug can be sold or not, it would be up to doctors to weigh all the risks and decide what’s best for their patients on an individual basis.
This a dangerous and naive view of informed medical choice. Front-line physicians don’t have the time, resources or skill to mount strict, comprehensive and authoritative analysis of drugs. GlaxoSmithKline’s Rosiglitazone Studies are no good to your family doctor. Moreover, doctors are swayed by drug marketing and browbeaten by patient advocating specific treatments.
- Editorial. Time to Ban Direct-to-Consumer Prescription Drug Marketing. Annals of Family Medicine 5:101-104 (2007).
Even worse, we can’t rely on uncoordinated third-party research specialists to study all of the effects of medicines that go to market, and we can’t rely on peer-reviewed journals to publish only good results.
Open access to the data is a good idea, but it is not enough. Public health cannot take place voluntarily or in a legal vacuum. We need regulation to enforce that open access, we need regulation to uncover harmful effects and screen for snake-oil ‘alternative therapies’, and we need regulation to free doctors and patients from biased sales pitches.
Absent this, informed choice about medical treatment is a myth.