A python's embrace? Insurance and the global clinical trial.

backgroundRegulatory barriers present significant challenges to clinical trial approval during both "peacetime" and pandemics, particularly for multi-country clinical trials sponsored by academic institutions and low- and middle-income countries (LMICs). While such barriers have been depicted as a "python's embrace", analyses of trial approval efficiency and ethical frameworks have largely overlooked clinical trial insurance.

methodsI interrogate the evolution of clinical trial indemnification mechanisms, rationales, and operationalisation over the past fifty years through a structured literature review. I then consider the procedural barriers faced by academic institutions conducting multi-country clinical research during the COVID-19 pandemic using a case study of the University of Oxford's "COPCOV" trial, which was led by the Mahidol Oxford Tropical Medicine Research Unit in Bangkok, Thailand. This includes thematic analysis of more than 65 semi-structured interviews with trial stakeholders and analysis of insurance documents from the Trial Master File and hundreds of stakeholder emails.

resultsSupplementary reinsurance policies cost over £110,000 during the COPCOV trial, delayed trial approvals by up to nine months in some countries, and were largely justified by sponsors based on concerns about reputational damage. I argue that risk frameworks grounded in financial risk management and the commercial sector have expanded within academic institutions and, when coupled with an expansion of national requirements for "local paper" insurance policies, create serious barriers to initiating trial sites in many LMICs.

conclusionsTwo potential reform pathways, which are grounded in procedural or systemic reforms and should be led by LMIC-based policymakers, could help to de-barrier clinical trial insurance procedures and ensure that evidence of efficacious (and affordable) countermeasures are available during future global health emergencies.