Re: Desperately seeking solutions

The pharmaceutical industry is not producing new treatments fast enough.  Not fast enough to justify the hype around the long list of “omics”.  Not fast enough to continue as highly profitable companies. These headlines are
everywhere.  One immediate reaction to these headlines is to affirm that the pharmaceutical business is not a hype industry.  Ethical medicines do not meld well with ASAP.  However, this fact does not help us to improve and invigorate the pharmaceutical business.

Research and development of new treatments is a difficult business – and, indeed, is difficult as the basis of a business.  With the rapidly increasing number of potential drug targets, and our greater understanding of the numerous ways drugs can interact with their targets – competitive, noncompetitive, use-dependent,
allosteric, etc. – the search for the best new chemical entity becomes more involved, slowing the process even more than in previous years.

Basic research, generally the purview of academic and individual investigators, is necessary to uncover the new diamonds in the rough.  But, as noted by Sharon Begley & Mary Carmichael in their article in Newsweek,
academic researchers are not prepared, or rewarded, for the “time-consuming drudgery” required to take an idea into drug development. Academic researchers are rewarded for publications and funded grants; their results don’t even have to be able to be replicated as long as they stimulate research and publications by others (see Science Citation Index). 

Perhaps more troubling is the rush to fund translational studies in the clinical setting.  At present the vast majority of clinical studies are run through pharmaceutical companies, directly or via clinical contract research organizations (CRO’s).  A critical factor governing these studies is the palpable fear of being spotlighted for scrutiny by the FDA.  Beyond the standard approval process, FDA scrutiny can fatally delay a project, be very expensive, and produce negative publicity.  Companies, certainly those that have been in business a while, work very hard to ensure their protocols align with FDA guidelines.  Of course, following FDA guidelines and approval is simply making sure the best and safest drugs are approved, but fear of the FDA is a quick way to put that into one's daily mindset. 

Now, we are seeing a trend towards pushing more of the early clinical development work into medical centers.  The goal is to get more potential treatments examined and hopefully translated sooner into new and better therapeutics.  At face value, this trend seems reasonable since medical centers are often where clinical trials are carried out.  BUT, when generated by pharmaceutical companies and CRO’s, clinical studies are carried out with full knowledge that the companies’ bottom lines are critically dependent on meeting FDA standards.  And,
while medical center staffs (nurses, etc.) carry out the studies, they do so at the command of the funding pharmaceutical company.

Medical centers are still often run as feudal societies, nobility (read physicians and other lettered professionals) and staff (read serfs).  We give physicians a lot of leeway in treating patients because they may have to make life and death decisions.  However, this can play out that it is difficult for staff to question physicians’ directives; physicians can change treatment regimens with little or no explanation.  And, physicians are trained to expect their plans to be carried out.  So, now, you have a situation where you have the FDA that expects to review and give consent on clinical trial protocols and changes to them before they are put into place, and physicians who expect to improve treatment as needed.  Given this polarity, it is difficult to imagine that there is not a tragedy in the making.

NIH’s CTSA centers and the ROADMAP in general are based on a no- repercussions philosophy, one that permeates medical centers and universities.  However, they are moving that into the realm of public safety.  It is clearly true that changes are critically needed to enhance the flow of good, novel therapeutics into the public health sector.  However, it is only pharmaceutical companies that have the experience, skills, and mindset (“fear of the FDA”) to carry this out.  I believe that NIH should be working to set up pharmaceutically-guided research institutes, not presuming that inexperienced (but really smart…) non-pharmaceutical investigators can pick up that role.  Drug discovery and development are simply outside the ken of those who have not personally experienced success and failure as part of pharmaceutical discovery and development.