Feasibility of post-authorization randomized controlled trials for conditionally authorized anticancer medicines – a multistakeholder perspective

Abstract

To generate comprehensive evidence for anticancer medicines that have been granted a conditional marketing authorization (CMA) based on single-arm trial (SAT) data, often, post-authorization randomized controlled trials (RCTs) are imposed. However, these PA-RCTs are sometimes delayed or not completed, thus raising questions on their feasibility and how this is assessed at time of marketing authorization. Here, we prospectively explored conditions and factors that contribute to or hamper the feasibility of PA-RCTs, from the perspective of various stakeholders that are directly involved in the conduct and approval of PA-RCTs. As such, a combination of qualitative research methods, i.e., exploratory interviews and focus groups with patients, physicians, medical ethicists and pharmaceutical industry was applied. Thematic analysis of the data obtained from the focus groups confirmed the three initial main themes that seem to directly determine the feasibility of PARCT: (i) design (i.e., trial aim and complexity), (ii) conduct (i.e., data collection, competition), and (iii) motivations to participate in, conduct, or approve a PA-RCT. Stakeholders’ motivations differed among them, but generally regarded their motivations to contribute to comprehensive evidence generation. Additionally, ‘conditioning factors’ were identified that may modify the relevance of the PA-RCT specific feasibility main themes, namely (i) cancer indication; (ii) promise of new product; (iii) need for evidence; (iv) development plan; (v) access to the product; (vi) location of trial. Mainly, perceived clinical equipoise, patient recruitment, and burden for patients and physicians may be concepts that overarch these feasibility considerations. Altogether, this exploratory study may contribute to advance PA-RCT feasibility assessments.