Tuesday, March 1, 2011

What is the Optimal Rate of Clinical Trial Participation?

The authors of EDICT's white paper, in their executive summary, take a bleak view of the current state of clinical trial accrual:

Of critical concern is the fact that despite numerous years of discussion and the implementation of new federal and state policies, very few Americans actually take part in clinical trials, especially those at greatest risk for disease. Of the estimated 80,000 clinical trials that are conducted every year in the U.S., only 2.3 million Americans take part in these research studies -- or less than one percent of the entire U.S. population.
The paper goes on to discuss the underrepresentation of minority populations in clinical trials, and does not return to this point. And while it's certainly not central to the paper's thesis (in fact, in some ways it works against it), it is a perception that certainly appears to a common one among those involved in clinical research.

When we say that "only" 2.3 million Americans take part in clinical research, we rely directly on an assumption that more than 2.3 million Americans should take part.

This leads immediately to the question: how many more?

If we are trying to increase participation rates, the magnitude of the desired improvement is one of the first and most central facts we need. Do we want a 10% increase, or a 10-fold increase? The steps required to achieve these will be radically different, so it would seem important to know.

It should also be pointed out: in some very real sense, the ideal rate of clinical trial participation, at least for pre-marketing trials, is 0%. Participating in these trial by definition means being potentially exposed to a treatment that the FDA believes has insufficient evidence of safety and/or efficacy. In an ideal world, we would not expose any patient to that risk. Even in today's non-ideal world, we have already decided not to expose any patients to medication that have not produced some preliminary evidence of safety and efficacy in animals. That is, we have already established one threshold below which we believe human involvement is unacceptably risky -- in a better world, with more information, we would raise that threshold much higher than the current criteria for IND approval.

This is not just a hypothetical concern. Where we set our threshold for acceptable risk should drive much of our thinking about how much we want to encourage (or discourage) people from shouldering that risk. Landmine detection, for example, is a noble but risky profession: we may agree that it is acceptable for rational adults to choose to enter into that field, and we may certainly applaud their heroism. However, that does not mean that we will unanimously agree on how many adults should be urged to join their ranks, nor does it mean that we will not strive and hope for the day that no human is exposed to that risk.

So, we're not talking about the ideal rate of participation, we're talking about the optimal rate. How many people should get involved, given a) the risks involved in being exposed to investigational treatment, against b) the potential benefit to the participant and/or mankind? For how many will the expected potential benefit outweigh the expected total cost? I have not seen any systematic attempt to answer this question.

The first thing that should be obvious here is that the optimal rate of participation should vary based upon the severity of the disease and the available, approved medications to treat it. In nonserious conditions (eg, keratosis pilaris), and/or conditions with a very good recovery rate (eg, veisalgia), we should expect participation rates to be low, and in some cases close to zero in the absence of major potential benefit. Conversely, we should desire higher participation rates in fatal conditions with few if any legitimate treatment alternatives (eg, late-stage metastatic cancers). In fact, if we surveyed actual participation rates by disease severity and prognosis, I think we would find that this relationship generally holds true already.

I should qualify the above by noting that it really doesn't apply to a number of clinical trial designs, most notably observational trials and phase 1 studies in healthy volunteers. Of course, most of the discussion around clinical trial participation does not apply to these types of trials, either, as they are mostly focused on access to novel treatments.

1 comment:

essay writer said...

These days the ratings are getting up above the roof and I am sure that it is an interesting thing to talk about. I am pretty sure that it is the same typical situation we were having in the startup.