The study’s funding source is also not a reliable indicator of the study’s sponsor. Many studies are funded by two or more entities (for example, multiple pharmaceutical companies), or by entities from different sectors (for example, commercial support and a federal grant). A study’s sponsor is generally defined as the holder of that study’s investigational new drug application, or IND. The IND is a document that details the sponsor’s clinical trial responsibilities, including the selection of qualified investigators, the documentation of proper clinical trial conduct, the monitoring of the study and investigation (or investigations), and the prompt relay of adverse event information to the Food and Drug Administration and participating investigators.
In the past decade, pharmaceutical companies have reduced the number of drug development trials conducted through academic institutions and, instead, have contracted much of drug development to clinical research organizations. Clinical trials constitute a hefty financial burden associated with clinical development, and academic institutions impose a hefty indirect cost or overhead. Some institutions demand percentages as high as 85% of the total direct cost, according to the Washington-based Federation of American Scientists. Academic bureaucracy and contention over intellectual property rights between institutions and pharmaceutical companies contribute to significant study delays. The emergence of independent institutional review boards has enabled investigators not affiliated with an academic institution to conduct clinical research. Collectively, pharma’s dependence on academic institutions for clinical trials has drastically eroded.
Criticisms of clinical trials
Criticisms of company-sponsored trials relate to scientific integrity and quality, from trial design to publication of all trial results, to conflicts of interest. These criticisms have gained an audience in medical journals and the media. In 2002, The New England Journal of Medicine (vol. 347, no. 17) published a study addressing “threats to the integrity of clinical trials in a research environment increasingly controlled by private interests,” for which there was significant publicity even before the actual publication. The study distilled surveys from 108 medical schools that were members of the Washington-based Association of American Medical Colleges and found that study contracts restricted investigators from accessing all trial data and rarely addressed data collection and monitoring. An AAMC executive interpreted the study as somewhat misleading: Only multicenter trials were included, and the study did not differentiate between school sizes, which can determine contract bargaining power.
Another 2002 publication in the journal CHEST (vol. 121, no. 4) raised concern about involving community-based physicians in company-sponsored trials, pointing to physicians receiving per-subject fees and the use of “non-institutional” review boards as potential compromises of scientific quality and subject protection. The case study was a placebo-controlled study of a corticosteroid for the treatment of asthma. Although the author acknowledged that a single trial cannot represent all industry-sponsored, randomized, controlled trials, the paper drew conclusions based on this case study (N=1) that warned of problems with “ethics in cardiopulmonary medicine.”
In 2003, a British Medical Journal review (vol. 326, no. 7400) explored the association between funding of drug studies and favorable outcomes for manufacturers’ drugs. The review concluded that company-sponsored studies were more likely to have outcomes favorable to the company than those sponsored by others, and that bias was systematic. One “rapid response” to the review stated that the paper was “at best misleading, and at worst confusing and inaccurate,” because the paper was not a review of primary studies, but a “review of reviews.” Another responder whose review was examined by the paper said the paper did not present his review’s main results, and speculated that this was because the main results were inconsistent with accepted opinions.
Critics guilty of same practices
Drug companies will continue to be major sources of funding for innovative research, and should improve their communication of all research results. On the other hand, industry critics fall prey to the same faults they have accused drug companies of: extrapolating results from one case study, as in the CHEST article; selecting parameters to yield desired conclusions, as in the NEJM research; and presenting what my graduate professors would call “hand-waving” as scientifically rigorous results (see the BMJ study). The ultimate objective is valid: Trials should be well-designed, have scientific merit and keep subject protection at the forefront. However, this objective may have become secondary to propaganda that serves no one, especially not patients.