Table 2 Considerations in assessing the appropriateness of specific innovative approaches in a clinical trial
CONTEXT | Clinical context | • What are the patients’ needs in this clinical context and disease setting? • What are the site and healthcare provider’s needs in this clinical context and disease setting? • Has the clinical context changed since the initiation of the study requiring the introduction of a new solution? • Did a COVID-19 infection change the clinical context and risk for patients within their primary disease? |
Context of use A. Related to the use of the innovative approach | • How will the innovative approach address the patient’s needs? • Will the approach address an important gap in access or equity in care? • Will the approach improve the patient experience in this study and is it feasible for this patient population? ◦ Has this been confirmed with patients/and or caregivers? • What are the benefits/downsides of using the approach for site/investigators/other healthcare providers in the study? • Will the innovative approach improve the site experience in this study? ◦ Has this been confirmed with the sites? • Will the innovative approach address a key gap in operational challenges? | |
B. Related to the use of the final study results | • What is the intended use of the study results? e.g. as proof of concept, or regulatory submission of the medicinal product and/or innovative approach. | |
EVIDENCE | Technical validation | • What data supports the use of the approach? i.e. are the data relevant and of adequate quality? • Has the approach been validated both in this patient population and disease setting? • What are the data gaps and mitigation steps? • Is the level of validation appropriate for how the innovative approach will be used in the study? And for the intended objective of the study? |
Clinical validation | • What are the benefits/downsides of using the solution for patients in the trial? • What data show that it can be used safely in patients and that it performs according to its specifications (if applicable)? • If the approach encompasses the use of a technology, is it safe for patients to use it? i.e. are there any risks associated with its use? Are there mitigation plans in place to ensure care continuity? | |
FEASIBILITY | Regulatory | • Is the approach and available documentation acceptable according to the local regulations? And what regulatory actions are needed to support implementation? • If digital tools are used, do they qualify as medical devices and do they have the required national certification/clearances? (e.g. CE mark in EU, FDA clearance in the US) • If the trial is already ongoing, does the incorporation of the approach need a protocol amendment? |
Data | • Does the approach introduce any risks related to data privacy? e.g. data access to unauthorised individuals or identification of study participants. • Does the approach support the collection of critical data to address the main objective of the study? • Does the approach pose risks related to the collection of reliable, consistent and complete data? i.e. any potential risks on the integrity of the study. • Are there any specific legal considerations? e.g. General data protection regulation in EU on data privacy. Are there any national restrictions on to use of the solution in specific countries beyond regulatory? • Is this technology collecting safety data? Consider the specific requirements. • Does the data collected follow the principles of FAIR (i.e. findability, accessibility, interoperability and reusability) data? | |
Ethical considerations | • Are there any ethical concerns about the use of the approach and in particular, could it enhance health inequity? e.g. introduces a technology that not all study participants have access/familiarity. • Does the informed consent form give enough information on the approach and its use? | |
Compliance | • Is the approach/technology compliant with the key international and national guidelines (e.g. GCP) and regulations related to privacy, accessibility, monitoring and patient inducement? • Is the approach/technology consistent with the sponsor’s standard practices and standard operating practices? If not, how will deviations be managed/recorded? • What are the potential risks if the patient does not know how to use the approach? • For approaches incorporating local labs/imaging, what are the related risks to data integrity and avoiding bias? What risk mitigation measures can be implemented to reduce the impact on data integrity? • If an external service provider will be used, what measures will be taken to ensure adherence to sponsor procedures? e.g. clearly defined responsibilities within contracts with sponsor oversight. • If local facilities are used, ensure collecting their certification and list of normal ranges (as applicable). | |
Operational | • How long (on average) would it take to implement this approach? For example, are contracts with specific vendors already in place? • Is the approach/technology easy to use by the site/investigator/patient? • Is training required to deploy the approach? Who requires the training? (e.g. principal investigator, patient, caregiver, nurses). Can the same training modules be used for all, or do we need to develop specific training for each group? How much time is required to organise the training? Is training available in the required languages? • Can this approach be implemented in all sites and countries? Is there appetite and interest from patients and sites in all countries? Can the approach be integrated into existing systems? • Can the approach/technology be widely deployed if necessary? • Is there enough vendor capacity and coverage? • Is special hardware needed to implement the approach, or can available hardware from patients/sites (e.g. smartphone) be used? • Can the study team procure and provide the hardware or other materials needed on time? Can the materials/resources be sourced locally to accommodate potential global supply issues? • Is there a process to solve issues identified by patients with the hardware (e.g. call centre)? • Is the approach cost-effective? What is the average cost (and cost model)? i.e. cost per patient, per site and per study. • If the approach is newly introduced into an ongoing study, how will the team document its introduction? Will the data be flagged with regard to how it was collected (e.g. remote collection of outcome data) to facilitate necessary sensitivity analysis? Can the change be flagged within the case report form? • Is there a way to monitor patient compliance through the study and a way to course correct if non-compliance is identified? • Is the data collected through the approach/technology easily accessible for the study teams to use and analyse? In what format? Can the data be integrated into company systems? • Are there any long-term considerations in deploying the approach? For example, what is the impact on subsequent studies? • Identify upfront the process for data flow to ensure integration into appropriate databases. |