Standard operating procedures for managing adverse events in trials that do not involve an investigational medicinal product: a protocol for a Delphi consensus study

The study will address variability in practice, defined in Standard Operating Procedures, that UK Clinical Trials Units (CTU) have in place for: i) defining, ii) classifying, and iii) reporting adverse events in non-CTIMPs. Compared to drug trials, adverse events in non-CTIMPs are not managed well. There is considerable inconsistency in reporting styles between trials of similar design and intervention type. To promote increased consistency, we will conduct a consensus exercise among non-CTIMP experts using a Delphi technique followed by a face-to-face meeting. This method adheres to the recommended sequence outlined by the international network for Enhancing the Quality and Transparency of Health Research (EQUATOR) for developing health research guidelines. A non-CTIMP expert is defined as: a CTU representative, a Chief Investigator or trial manager of non-CTIMPs with >3 trials experience in this role, or a senior member of the Health Research Authority’s Operations team or Ethics Committee. As such, the participants in the consensus exercises will also be the direct beneficiaries from the project maximising its pathway to impact. Following the face-to-face meeting — guidance and explanatory statements will be drafted. The guidance statement will focus on: • how adverse events should be defined in relation to the non-pharmacological intervention, • how CTU standard operating procedures should be designed to reflect the results of the Delphi exercise, • how adverse events should be classified following a judicious causal assessment, and • recommended reporting methods that will promote more effective meta-analyses of non-pharmacological interventions that provide a balanced benefit-harm evaluation. Following study completion, we will work with a selection of UK CTUs to evaluate the implementation of any agreed modifications to current practice.