Post-Marketing Trials Viewed as Marketing Ploy

ODENSE, Denmark, June 21 ? Doctors evaluating agents in drug-company-sponsored post-marketing trials may become inappropriately seduced by familiarity.

That's according to researchers here, who found that when physicians take part in these studies, their familiarity with the drug being evaluated makes them more likely to use it in everyday practice, suggesting that post-marketing trials are an effective sales tool.

But taking part in a sponsored trial does not appear to alter how physicians follow clinical guidelines for asthma, wrote Morten Andersen, M.D., Ph.D., and colleagues, of the University of Southern Denmark here and the University of Aarhus in the June 21 issue of Journal of the American Medical Association.

"Our study confirms the hypothesis that physician involvement in clinical trials is a powerful tool for influencing company-specific drug preferences," the investigators wrote. "Several mechanisms may be responsible, including setting up a gift relationship by payment to the trial-conducting physicians."

In an accompanying editorial, Bruce M. Psaty, M.D., Ph.D., of the University of Washington in Seattle, and Drummond Rennie, M.D., of the University of California San Francisco, and a deputy editor of JAMA, wrote that the public would be better served by large-scale studies looking at the risk and benefits of therapies over the long term, rather than these small, short-term trials that are as much about marketing as they are about medicine.

Dr. Andersen and colleagues conducted a retrospective cohort study designed to determine how company-sponsored trials might influence participating physicians' adherence to international treatment guidelines/recommendations and their choice of the sponsoring companies' products.

They evaluated 10 practices in Funen County in central Denmark whose physicians and patients took part in a drug-company sponsored clinical trial of asthma medication from April 2001 to October 2002, and compared them with 165 control practices that did not take part in the trial.

The investigators looked at 5,439 patients from the trial practices who were taking asthma medications, and compared them with 59,574 patients from the control practices.

The phase-IV trial was an open-label, multicenter randomized study comparing two doses of the same drug, Symbicort Turbuhaler (a fixed combination of budesonide and formoterol).

The trial was conducted by general practitioners who were responsible for recruiting patients and seeing them at three follow-up visits. For each enrolled patient, the physicians were paid the equivalent of (5,000 Danish kroner) by AstraZeneca.

The asthma trial was approved by an ethics committee and the Danish Medicines Agency. It appears that neither a methods paper nor a results paper from that study has been published.

The JAMA study endpoints were adherence guidelines, measured as the use of inhaled corticosteroids among asthma patient, how often the sponsoring company's drug was used, and the company's share of the total volume of asthma drugs used.

The researchers found among patients in the practices who were taking part in the trial that the prevalence of inhaled steroid use increased from 68.5% at baseline to 72.9% during the second year of observation. This increase almost exactly mirrored that among patients in the control practice, where the prevalence of inhaled corticosteroids rose from 69.1% to 73.3% over the same period.

Among non-trial-conducting practices the sponsor's share of asthma drugs declined slightly over the course of two years from 52.8% to 51.9%; but among trial-conducting practices during the same period, the sponsor's share increased from 52.9% to 58.7% (between group difference, 6.7%; 95% CI, 3.0%-11.7%).

But in the practices that were taking part in the trial, the sponsoring company's shares of the total prescribed volume of asthma drugs increased by 6.7% (95% confidence interval. 3.0%-11.7%), compared with practices not involved in the trials.

The difference in prescription patterns between the groups could be chalked up to "a significantly higher preference for the company's inhaled corticosteroids (odds ratio, 1.26; 95% CI, 1.04-1.54) and trends toward increased prescribing of the company's other asthma drugs," the investigators wrote.

"If we had access to information on the costs of the trial, it would have been possible to evaluate if these trial costs were counterbalanced by the revenue from the trial sponsor's increased market share," the investigators wrote. "Whether conducting a clinical trial can lead to minor improvements in guideline adherence can only be addressed in large-scale studies," they added.

In their editorial, Dr. Psaty and Dr. Rennie noted that post-marketing trials may help to elucidate the specific benefits of a class or drugs, but may also serve to muddy the waters when competition rather than clinical enlightenment is the primary goal.

"For the lipid-lowering statin drugs, for instance, the large long-term clinical trials have provided robust evidence about their health benefits in preventing cardiovascular complications of high levels of cholesterol," " they wrote. "On the basis of this evidence, the indications for the statin drugs have expanded, statin drug sales have increased, and the health of the public has improved."

"On the other hand," they added, "the choice of inferior active comparison treatments in some of the industry-sponsored large long-term randomized trials in hypertension bespeaks commercial influence.".

The editorialist also cited recommendations from the Office of the Inspector General of the U.S. Department of Health and Human Services, which in a guidance letter to pharmaceutical companies states that "post-marketing research activities should be especially scrutinized to ensure that they are legitimate and not simply a pretext to generate prescriptions of a drug."