The core question is whether a CRO is truly independent because (as its defenders claim) it won't get research grants in the future unless it keeps a good reputation for high quality work, and it works for no single drug company; or is ultimately the creature of the industry because (as its critics claim and as I review in HOOKED) in the end, if you don't give drug firms the results they want to market their product, they'll take their business elsewhere. Lenzer gives many examples, mostly drawn from the world of academic CROs, that at least hint strongly at the existence of a decided pro-industry tilt that could seriously bias the research results. She also gives somewhat clearer evidence of a money-laundering operation--that the med school can form an academic CRO, the CRO can take money from a drug company, med school faculty can conduct the research, and when the study is published, all the publicity states that faculty at the med school discovered such-and-such, with nary a mention of the CRO or the company sponsorship.
What I took to be the major pearls from the paper--in the form of smoking guns, to mix metaphors--were:
- One of the relatively few major trials demonstrating that serotonin-type (SSRI) antidepressants work in children and teenagers was the TAPS (Treatment of Adolescent Depression) study. This study was carried out by Duke University's academic CRO. The drug under study was Prozxac, made by Eli Lilly. The CRO does a fair amount of work for Lilly. Officially, the TAPS study was sponsored by the NIH. Lilly presumably simply donated the drug. However, TAPS has a number of design features that suggest a considerable bias in favor of Prozac. The worst was the fact that a couple of the arms of the trial were non-blind, when they just as easily could have been blinded, and the non-blind data accounted for a great deal of the total effect size atributed to Prozac. Lenzer noted another bias-suggestive feature--that the scoring system reported those who did better on the drug but omitted any mention of the number who did worse. She then tried to obtain the raw data, on how many did worse, from both the NIH and the principal investigator at Duke. The NIH refused, saying these data were in the possession of the PI. The PI and Duke refused to disclose those data. For a "publicly funded" study this seems strange behavior indeed.
- Quintiles Transnational, based in North Carolina, is the world's largest CRO. Its founder and CEO, Dennis Gillings, recently donated $50 million to UNC's School of Public Health--now named the Gillings School of Global Public Health. UNC's chancellor, in writing to Gillings to thank him for the gift, stated that in return, the School would commit to "alignment of faculty behind focused programs," with the priority to be "new methodologies to speed clinical trials innovation." Now, this is odd. A school of public health as a rule is not in the pharmaceutical clinical trials business. If there is any school at the university that you'd expect would be looking at the importance of non-drug approaches to health problems, the School of Public Health would be it. Lenzer also noted that 8 current or former Quintiles executives now either head school programs or sit on advisory boards. Hmm--sounds like a CRO just bought a school of public health--and that UNC meekly handed it over.