Further adding to these weak findings was what the authors found when they reviewed the actual documents from the Warner-Lambert settlement. Documents found on the Drug Industry Document Archive (DIDA; http://dida.library.ucsf.edu) indicate that authors of 8 of the 29 articles referenced above may have taken part in a company-sponsored meeting, been paid as a speaker, or worked with ghostwriters. Unfortunately, information available from DIDA was not sufficient to directly tie an individual author’s specific involvement with Pfizer or Warner-Lambert to their work on specific publications.4
The Journal of Psychiatric Practice supplement article documents how drug marketing can influence publication in scientific and clinical research literature as backdoor, off-label drug marketing. Prescribing professionals should be aware of the damage that such tactics can cause in individuals who were prescribed an ineffective drug by physicians mistakenly relying on what they believed to be emerging literature supporting its efficacy.
The tactics used to market Neurontin should be a wake-up call as cases of off-label marketing continue to flow through the legal system. In 2008, Pfizer settled lawsuits costing more than $60 million in 33 states and Washington, DC, for charges that the company used illegal tactics to off-label market its drug Celebrex. As recently as early 2009, Eli Lilly and Company pleaded guilty and paid $1.4 billion for promoting Zyprexa for unapproved uses—such as treatment for dementia in the elderly.
Scrutinizing the literature
Given the prevalence of these cases, it’s imperative that physicians and other prescribing professionals scrutinize the medical and scientific literature with the awareness that sometimes scientific publication is part of an organized marketing campaign.
A standardized protocol on how to conduct such scrutiny might make the task less burdensome and time-consuming. When reading case series or cohort studies, professionals should view articles through an evidence-based prism and ask the following questions when reading literature supporting the off-label use of any drug:
1. Are the case studies presented clearly and completely, with full disclosure by the author(s)? There is relatively little guidance on how to evaluate the quality of a case study, but an article appearing in the journal Spine5 suggests that high-quality case studies should have the following:
• Questions that are clearly defined.
• Study populations and results that are well described.
• Outcome measures that have been validated.
• Appropriate statistical analyses.
• Discussions and conclusions clearly supported by the data.
• Funding sources that are fully dis- closed or, when no funding source exists, a statement to that effect.
2. Is there an inexplicably small group of individuals repeatedly publishing positive case series without follow-up controlled trials?
3. What is the quality of the peer review of the journals in which the studies are being published? Are there published policies regarding peer review and conflict of interest disclosure?
4. Are the funding sources of studies disclosed? If so, are the studies being funded by the company that owns the drug? If not, have the authors received funding from the company that owns the drug?
5. Do the studies make sense? For instance, if the illness is chronic, do case series studies only present short-term results or do conclusions from randomized controlled trials (if available) contradict conclusions/recommendations from case studies?
Just as no 2 manufacturers produce the same quality cars, computers, or televisions, the same is true for the articles produced by authors, editors, and publishers. The discovery that relatively few individuals could significantly affect the literature shows why clinicians and researchers must apply their own judgments when considering off-label uses for their patients. Part of this process should involve reading articles carefully to identify weaknesses and missing information within the articles themselves, and then comparing articles across journals to see whether the weaknesses have been adequately addressed elsewhere. Systematic reviews, conducted by researchers without conflict of interest, are one way to efficiently sort through the literature. Unbiased online resources such as the Drug Effectiveness Review Project (http://www.ohsu.edu/drugeffectiveness) or the Agency for Healthcare Research and Quality (http://effectivehealthcare.ahrq.gov) are particularly helpful.
Finally—and perhaps most important—prescribing professionals must temper anything they read with their 2 most important tools: experience and common sense.