Trials & Tribulations: Studies on the fate, transparency and efficiency of clinical drug trials

Abstract

Efficiency and transparency of clinical drug research needs improvement In the Netherlands, approximately 600 clinical drug trials are annually reviewed by the accredited Institutional Review Boards (IRBs). What happens with these trials after IRB-approval is unknown. In his thesis entitled “Trials & Tribulations. Studies on the fate, transparency and efficiency of clinical drug trials”, Sander van den Bogert analyzed how many clinical drug trials reach their optimal fate. Furthermore, he investigated how data collected by regulatory agencies can be used to facilitate risk-based approaches to the supervision of clinical drug trials. The project was a collaboration between the Utrecht Institute for Pharmaceutical Sciences, the National Institute for Public Health and the Environment, and the Dutch regulatory authorities for medicinal products (CCMO, CBG and IGZ). The main finding, described over five studies in chapter 2, was that of all clinical drug trials that were reviewed by all Dutch IRBs in 2007, 45% were justified completed and had published their primary outcomes (according to the original protocol) in the scientific literature, after 8-9 years of follow-up. This implies that the investments in more than half of the clinical drug trials are (partially) wasted and that the ethical obligation of publishing the findings of a study involving human participants is often being violated. Moreover, it implies a substantial bias in the scientific literature because the findings of the unpublished trials are most likely unfavorable for the investigators, or sponsor. Chapter 3 describes a literature study, to identify potential reasons and causes for selective reporting of clinical drug trials. A hypothetical causal scheme was developed, distinguishing necessary causes from component causes and individual factors from factors related to the wider environment. The scheme illustrates that the causes of trials not reaching their optimal fate are complex and multidimensional. Furthermore, the scheme can be used to develop policy interventions to improve the transparent reporting of clinical trials. Chapter 4 investigates the international platform of drug development. This chapter contains a comparison of the phase 3 clinical trial landscape in the EU between oncology and psychiatry, showing that recent success results in a large difference in drug development activity. Chapter 4 also demonstrates that small companies are more likely to obtain a license for their new compound if they collaborate with the larger pharmaceutical industry during the clinical development stage. Finally, in chapter 5, a taxonomy of risk indicators is presented that can be used to inform risk-based approaches to clinical trial supervision, for example by Good Clinical Practice inspections. Chapter 5 discusses that the indicators can be translated into a quantitative risk model, but that the context of a trial cannot completely be captured by indicators. Furthermore, supervisors still need to cope with a trade-off: where the potential harm is high, is the likelihood of violations low.