Issue 24 / 25 June 2012

POSTMARKETING research into a new drug might seem like an unambiguously good thing.

After all, what could possibly be wrong with an attempt to evaluate safety and efficacy in a real-world setting, as opposed to the more rarified environment of the clinical trial?

Well, nothing — if that was actually what the studies were designed to do.

Unfortunately, postmarketing observational studies are often designed to boost sales of a drug rather than to make any genuine attempt to assess its risks and benefits, according to articles published in the BMJ this month.

Postmarketing studies tend to be far less scrutinised than phase II and III trials, leaving sponsoring companies free to tinker with their statistical analysis, report results selectively, and generally do everything they can to promote positive messages about their product while downplaying any less advantageous findings.

The BMJ papers suggest that companies keen to promote a new treatment over older — and generally cheaper — options may also see the studies as a means to change prescribing habits of participating physicians.

In a scathing review of postmarketing studies of insulin analogues, Professor Edwin Gale, an endocrinologist from the University of Bristol in the UK, found most were performed in middle- or low-income countries, had limited scientific value, and promoted wider use of more expensive insulins.

Many failed to ask a clear or novel research question, lacked any comparator group, and seemed larger than needed to answer the questions proposed, he writes.

When it comes to assessing the validity of research findings, we tend to assume bigger is better, but Professor Gale suggests these excessively large and loosely supervised studies are in fact unlikely to produce much information of value.

In fact, the gargantuan size of some studies may be more about recruiting the maximum possible number of doctors in the hope of persuading them to switch patients to the sponsoring company’s treatment than about any desire to improve statistical power.

“Participating physicians, particularly those with no previous research experience, may participate in good faith, unaware that one aim of the study is to influence their prescribing habits”, Professor Gale writes.

“Their judgment is nevertheless open to question, particularly when their own participation is remunerated and their patients are exposed to extra cost for little benefit.”

Evidence-based reviews have consistently concluded insulin analogues offer little benefit to most people with type 2 diabetes (other than those with troublesome hypoglycaemia), yet they cost 2–4 times as much as human insulin, Professor Gale writes.

A second BMJ paper offers an insider’s view of industry motivations for doing this kind of research.

Written by a former employee of a major drug company, the article reveals how the company omitted negative results from published findings or “played” with the statistical analysis when it failed to reveal the desired result at the first go.

The “lax” protocols of postmarketing studies made this kind of manipulation possible, the anonymous author writes.

“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.”

Making it even worse is the fact that the costs of this questionable research are often borne by patients or the public purse.

While companies front up for incentives paid to doctors and for administrative expenses, the cost of the drugs themselves tends to be laid at the door of patients, their insurers or the health system.

Professor Gale sums it up: “The patient or healthcare system pays for a more expensive agent instead of one that is cheaper and equally effective, and the public is offered misleading claims of comparative merit based on studies of limited scientific value.”

Industry involvement in clinical research has come under a lot of scrutiny in recent years, but attention has mainly focused on studies designed to bring a drug to market.

It seems it’s time to cast the net a little wider.

Jane McCredie is a Sydney-based science and medicine writer.

Posted 25 June 2012

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