Abstract
Deficient adherence to trial protocols including dosing errors introduces uncertainty about the reliability of clinical trial results. Traditional ways of measuring compliance have been challenged since studies using electronic monitoring to register opening of medication containers have revealed that patient reporting and residual tablet counting tend to overestimate compliance with dosing regimens.
Application to the Medical Products Agency for approval of all clinical trials performed in Sweden on medicines involving human subjects has been obligatory since 1984. The number of applications has ranged from 394 to 675 per year. Among over 1,000 clinical trial applications between May 2004 and February 2008, compliance or adherence was mentioned in the study objectives of only two applications.
Clinical trial applications that combine adherence information with clinical outcome are still rare in Sweden. Phase 3 clinical trials are designed to provide sufficient evidence of efficacy to support marketing authorization. Patients are typically analyzed according to assigned group (intention to treat principle) rather than according to actual treatment received in order to ensure that an identified treatment effect is due to the treatment itself and not a result of postrandomization bias. Taking account of compliance information is therefore mainly considered as supportive evidence except for noninferiority clinical trials. However, electronic capturing of compliance information in clinical trials may have an important role in advancing our understanding of the relationship between drug dose or concentration and therapeutic efficacy or adverse reactions.
Ways to optimize information from clinical trials are encouraged from a Swedish regulatory perspective and are expected to increase study efficiency.
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