Monday, October 4, 2010

Proposal for Pagoclone Drug Trials

It can take a billion dollars, thousands of patients, and more than a decade to gather evidence to approve a new drug. A big part of the problem with conventional trials is that they essentially take all comers. In some cases researchers might know that some participants may not benefit from the treatment. Those who do not respond can cause a drug to fail even though a significant minority of patients could benefit.

Unless something different is done, we may have to wait a very long time for a fluency improving drug. Perhaps the problem lies in the current policy that it is necessary to absolutely, positively prove (e.g., to the 99.9999% level of certainty) the efficacy of the drug before releasing it to the public. For any potentially fluency improving drug such as pagoclone, we might expect all sorts of objections to be raised when the results of any clinical trials are published. For example, although improvement may have been observed in a clinical setting, will this improvement be observed post-clinically after a long period of time? Is the disfluency counting method reliable? Etc., etc.

The most vociferous critics of fluency drug testing (e.g., The Stuttering Brain blog; Roger Ingham, Journal of Clinical Psychopharmacology, October, 2010) rely heavily on the placebo argument to bolster their beliefs and prejudices--namely that individuals respond favorably to a particular drug not because of its therapeutic efficacy but rather through a placebo effect. And, according to them, this effect might be short lived. Since stuttering is basically a mind-body problem, and the mind plays a very important role in the severity of the disfluency, it is no wonder that it is very difficult to disentangle any real therapeutic effects from placebo effects. In addition, naturally occurring fluctuations in the levels of neurotransmitters may further obfuscate clinical trials. Listening to these critics may result in paralysis through analysis with regard to the search for fluency enhancing drugs.

So my proposal is that for such a drug like pagoclone, why not release the drug on the market AFTER testing for safety? In this way, a population larger than that of any clinical trial could try the drug and decide for themselves as to its efficacy. In essence, it will be the market that decides its success or failure. For some, the drug may prove to be a boon to their fluency, while for others the effect may wear off after time. If the effect does wear off, it does not necessarily imply a placebo effect. An alternative explanation might be that tolerance to the drug may have been built up. In which case, for these people, the drug would better be used in a punctuated fashion with periods of use separated by periods of no use. And, of course, there may be a group for whom the drug does not work at all.

The final concern would be the cost of the drug to the consumer if it were released in this fashion. In the ideal, the cost of a drug that has less than strongly proven efficacy should be less, since the cost of excessive testing was substantially reduced. However, given that the capitalistic system is what it is, perhaps the government should step in and regulate not only the release of such drugs, but also their cost, much as governments often regulate the prices that utilities charge for their products or services.

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