Are drug trials too exclusive?

When I wrote recently that Medicare bases its reimbursement decisions on trials that largely exclude the elderly population (Tested on the young, used on the old), Cor Doc commented –quite rightly– that there may be good reasons for this:

There are difficulties performing clinical trials in the elderly population. This is most often due to multiple comorbid illnesses in the older patients. Trials are usually designed to exclude such subjects lest their other illnesses cloud the outcome of the study and cast into doubt the significance of the results. Performing clinical trials is challenging to begin with because we are constantly assessing a sample of the general population and then applying these results to the world-at-large. The same statistical flaws can therefore theoretically affect clinical trials as they can New Hampshire poll results.

While we would love to study outcomes in a target population with every intervention, researchers hold sacred the validity of their results. Having results as iron-clad as possible, therefore, means that one must remove any confounding variables.

Three years ago I looked into a related topic –the proliferation of exclusion criteria in pharmaceutical clinical trials. Many of these trials were designed in a sloppy manner: exclusion criteria were added without a clear rationale, in a way that made the trials hard to conduct and the results less useful.

In a 2002 article in the American Journal of Psychiatry, Posternak et al. studied exclusion criteria in drug trials and made this conclusion:

Many of the standard exclusion criteria currently used in antidepressant efficacy trials may not be achieving their intended goals of maximizing drug-placebo differences. The practice of excluding subjects with particular clinical profiles, which greatly reduces the generalizability of antidepressant trials, appears to lack empirical support.

Posternak’s study was based on trials in the 1990s, but the phenomenon was alive and well a decade later. As one researcher said:

Companies are making exclusion criteria too narrow to the point that it’s very difficult to meet enrollment expectations. Oftentimes they are also vaguely defined, such as excluding those with borderline personality disorder without specifying how such patients are to be identified.

Let’s hope designers of trials are being more thoughtful these days.

February 5, 2008

One thought on “Are drug trials too exclusive?”

  1. Recently published on

    The Human Injury of Lost Objectivity

    If I were to rate the corruptive tactics performed by big pharmaceutical companies, the intentional corruption of implementing fabricated and unreliable results of clinical trials by pharmaceutical companies by hired third parties who manipulate these trials they sponsor because of their power to control others involved in such trials that is largely absent of regulation would be at the top of the list, and likely the most damaging to the requirement of authenticity and, more importantly, assuring the safety of the public health, as I understand that this does in fact occur.
    Decades ago, clinical trials were conducted at academic settings that focused on the acquisition of knowledge and the completely objective discoveries of meds. Then, in 1980, the Bayh-Dole Act was created, which allowed for such places to profit off of their discoveries that were performed for pharmaceutical companies in the past. This resulted in the creation of for-profit research trial sites, called Contract Research Organizations, which is often composed of community research sites with questionable investigators possibly void of necessary research experience or quality regarding their research purpose and ability. Since they are for- profit, with some CROs making billions of dollars a year. The trials conducted at such places are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial being conducted involving their med being studied in the trial. This coercion is done by various methods of deception in subtle and tacit methods. As a result, research in this manner has been transformed into a method of marketing, which includes altered results of the trial to favor the sponsor’s med. Their activities are absent of true or applied regulation, and therefore have the autonomy to create whatever they want to benefit what may be a collusive relationship between the site and the sponsor.
    Further disturbing is that once the creation of the trials is completed, they are then written by ghostwriters often, although no one seems to know how often. These people are not identified and acknowledged by the sponsor, and may not be trained in clinical research overall, as they are simply freelance writers, as one does not need research training or certification in order to perform this function. Rarely do trial ghostwriters question their instructions about their assignment, which is clearly deceptive and undocumented by the sponsor. Also, these hired mystery writers are known to make about 100 grand a year. This activity removes accountability and authenticity of the possibly fabricated clinical trial even further. The corruptive act is finally completed by the sponsor hiring an author to be placed on the trial that likely had no involvement with the trial, and, along with others, was paid by the sponsor for doing this deceptive act.
    To have the trial published, the sponsor pays a journal to do this in various ways, I understand, such as purchasing thousands of reprints of their study from the journal. Again, how often this process is performed is unknown, yet frequent enough to create hundreds of such false writers and research sites to support the pharmaceutical industry. So benefits of meds studied in such a malicious way potentially can harm patients and their treatment options and safety risks. The purchased reprints are distributed to the sponsor’s sales force to share the content with prescribers which may lack validity.
    Such misconduct discussed so far impedes research and the scientific method with frightening ethical and harmful concerns, if in fact true based on reports by others. If so, our health care treatment with meds is now undetermined in large part with such corruptive situations, as well as the possible absence of objectivity that has been intentionally eliminated. Trust in the scientific method in this type of activity illustrated in this article is absent. More now than ever, meds are removed from the market are given black box warnings. Now I understand why this may be occurring.
    Transparency and disclosure needs to happen with the pharmaceutical industry for reasons such as this as well as many others, in order to correct what we have historically relied upon for conclusive proof, which is the scientific method. More importantly, research should not be conducted in a way that the sponsor can interfere in such ways described in this article, requiring independent sites with no involvement with the drug maker. And clearly, regulation has to be enforced not selectively, but in a complete fashion regarding such matters. Public awareness would be a catalyst for this to occur, after initially experiencing a state of total disbelief that such operations actually are conducted by such people, of course. We can no longer be dependent on others for our optimal health. Knowledge is power, and is also possibly a lifesaver.

    “Ethics and Science need to shake hands.” ……. Richard Cabot

    Dan Abshear

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