Analysis

Post-marketing observational studies: my experience in the drug industry

BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e3990 (Published 12 June 2012) Cite this as: BMJ 2012;344:e3990

I was an employee of a major drug company for more than seven years. During most of that time I was part of the medical department, which was responsible for designing, conducting, and publishing clinical research. I was mainly involved in post-marketing observational studies. These studies are challenging because of their observational nature, very different from the controlled settings of phase II and III clinical trials. In theory, post-marketing studies are primarily used to answer an important clinical question: “Is this drug effective and safe in a non-controlled, real life setting?” However, some of the studies I worked on were not designed to determine the overall risk:benefit balance of the drug in the general population. They were designed to support and disseminate a marketing message.

Whether it was to highlight a questionable advantage over a “me-too” competitor drug or to increase disease awareness among the medical community (particularly in so called invented diseases) and in turn increase product penetration in the market, the truth is that these studies had more marketing than science behind them.

Since marketing claims needed to be backed-up scientifically, we occasionally resorted to “playing” with the data that had originally failed to show the expected result. This was done by altering the statistical method until any statistical significance was found. Such a result might not have supported the marketing claim, but it was always worth giving it a go to see what results you could produce. And it was possible because the protocols of post-marketing studies were lax, and it was not a requirement to specify any statistical methodology in detail. On the other hand, the studies were hypothesis testing (such as cohort studies, case-control studies) rather than hypothesis generating (such as case reports or adverse events reports), so playing with the data felt uncomfortable.

Other practices to ensure the marketing message was clear in the final publication included omission of negative results, usually in secondary outcome measures that had not been specified in the protocol, or inflating the importance of secondary outcome measures if they were positive when the primary measure was not.

Although the medical department developed the publication plans, designed the study, performed the statistical analysis, and wrote the final paper (which when published was passed on to marketing and sales to be used as marketing material), the marketing team responsible for that product were directly involved in all stages. They also closely supervised the content of other educational “scientific” materials produced in the medical department and intended for potential prescribers. Instructions from marketing to the medical staff involved were clear: to ensure that the benefits of the drug were emphasised and the disadvantages were minimised where possible.

Carrying out large post-marketing studies was also a great opportunity to increase product name recognition by recruiting lots of patients via prescribers. A small group of these investigators would also act as so called key opinion leaders and would become part of the company’s advisory boards. These were clinicians, usually experts in the subject of study, and key prescribers and influencers. Every big international observational study had a large advisory board. This was critical since the success of a newly launched drug in the market would depend on how many key opinion leaders were part of the study. Not only would they add credibility to the results, but they would also be key in influencing decision makers and other prescribers. In regional studies with thousands of patients, the study’s advisory board was formed by at least one key opinion leader from each country in that region, ensuring that areas important in terms of possible sales were covered. The contributions of the key opinion leaders to the study were always positive, but in my experience more directed towards designing new studies to answer their specific clinical questions rather than critically appraising our results and conclusions. In general, the relationship was amicable. We took them to the best hotels and restaurants during our advisory board meetings, and they appeared as authors in our research. Later, they would act as the company’s “ambassadors,” giving conferences, teaching doctors, or talking to the media about the benefits of the drug.

A drug is profitable for as long as its patent lasts. The patent lasts for 20 years, and drugs are patented as soon as they show some pharmacological activity as chemical compounds. Of those 20 years, 12 are spent on drug discovery, preclinical and clinical research, and receiving approval by the relevant regulatory agency. That leaves eight years to recover the millions of dollars invested. These are average numbers. Sometimes one of the stages is delayed, leaving less “patent time” available to make a profit. So the pressure is on.

However, this does not justify drug companies engaging in questionable practices. Allowing companies to focus more time and efforts on drug development, or increasing transparency by encouraging industry authors to disclose the fact that the research has commercial objectives (as long as these are balanced with scientific value) would definitely help to develop better drugs for patients. And by better, I mean innovative, more effective, and safer drugs, not necessarily just more profitable.

Notes

Cite this as: BMJ 2012;344:e3990

Footnotes

  • doi:10.1136/bmj.e3974
  • , doi:10.1136/bmj.e3987
  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.