Tuesday, July 29, 2014

More on Guinea Pigging--The Quality of Pharmaceutical Research

Two longish articles by our old friend Dr. Carl Elliott and by Peter Aldhous:
--raise interesting questions about clinical research on pharmaceuticals.

Dr. Elliott addresses the selection of subjects for research on new drugs, and shows that in many instances, they are taken from places that raise suspicions about the quality of the research--such as homeless  shelters, and other places that have a high incidence of mentally ill. Aldhous looks at the credentials of the physicians who do this research and shows that some cases, the physicians have been disciplined for serious violations.

Perhaps the best short summary of these two pieces appears toward the end of the Aldhous piece:

"Some experts agree that the FDA's entire rulebook for clinical trials, with its talk of things like 'institutional' review boards, reflects the academic past of clinical research--not today's industrial juggernaut of for-profit clinical trials firms and for-hire review boards, which oversee a workforce of doctors drawn from regular medical practice. 'They are regulations for a world that doesn't exist anymore,' says Elizabeth Woeckner, president of Citizens for Responsible Care and Research, which campaigns for the safety of medical research volunteers."

Therefore, when one reads that scientists have tested new drugs on patients and have yielded the following information, one has to wonder, first, whether those "patients" actually have the diseases the scientists are studying and have honestly reported their status (as opposed to making up what seems most fitting for payment for inclusion in the study, and getting away alive afterwards); and second, whether those "scientists" are properly trained physicians and can observe the variables required. There seems little concern, presently, to reassure the public that either is the case.

Monday, July 28, 2014

Rating New Hepattits Drugs: What Standard?

There seem to be two problems with the newest drugs for hepatitis C,  simeprevir (Olysio) and sofosbuvir (Sovaldi). The problem most discussed these days is "miracle drugs cost too much." For example, guru David Blumenthal, MD, holds forth on the Commonwealth Fund website--
--that Sovaldi is "dramatically effective and extraordinarily expensive." Robert Steinbrook and Rita F. Redberg, in an editorial in JAMA Internal Medicine, declare the new drugs "a scientific triumph". They then go on to note the problem--that Sovaldi can cost $1000 per tablet for 12 weeks' treatment, putting the cost at $84,000 ($168,000 for 24 weeks).

Our old friend Dr. Roy Poses at Health Care Renewal seems to be one of the few who's discussing a radically different problem--"maybe the drugs that cost so much are not miracle drugs at all." In his latest post: http://hcrenewal.blogspot.com/2014/07/sovaldi-quantum-leap-backwards-to-days.html--
he highlights the most recent article in JAMA, which is fawned over in an accompanying editorial despite the fact that it's non-randomized and non-controlled. Dr. Poses points out that the FDA decided to approve Sovaldi as a "breakthrough drug" which seems to have undercut the requirements that it be documented by something akin to science.

The article that accompanied the editorial in JAMA Internal Medicine addressed an evidence report by the Institute for Clinical and Economic Review, Boston, prepared for a meeting of the California Technology Assessment Forum. They concluded a need for caution regarding the two newest drugs:
"First, the evidence base on the comparative clinical effectiveness of these 2 new drugs remained thin in most areas and notably incomplete in others. For example, in some subgroups, such as patients who have failed earlier treatments, there were little or no data available. There were no long term data demonstrating the durability of short-term sustained virologic response rates for either drug; nor had either drug been compared head-to-head in a randomized clinical trial with each other or with a first-generation direct-acting antiviral drug. Finally, the evidence necessary for sofosbuvir to gain marketing approval through the FDA’s breakthrough designation was particularly sparse and did not include requirements for controlled trials." They noted that as a result of this presentation, the California forum voted the use of these drugs a "low value" for the health system.

Steinbrook and Redberg noted that Sovaldi had grossed $2.3B in the first quarter of 2014. So "low value" by one standard seems to be pretty high value by another. If the past is any indication, it will be some years before we find out which standard is the correct one; and meanwhile, the profiteers at the makers of the two drugs can expect a killing.

Steinbrook R, Redberg RF. The high price of the new hepatitis C virus drugs. JAMA Internal Medicine 174:1172, 2014.

Ollendorf DA, Tice JA, Pearson SD. The comparative clinical effectiveness and value of simeprevir and sofosbuvir for chronic hepatitis C infection. JAMA Internal Medicine 174:1170-71, 2014.