Informed consent and trial prioritization for clinical studies during the COVID-19 pandemic. Stakeholder experiences and viewpoints.

BACKGROUND: Very little is known about the practice-oriented challenges and potential response strategies for effective and efficient translation of informed consent and study prioritization in times of a pandemic. This stakeholder interview study aimed to identify the full spectrum of challenges and potential response strategies for informed consent and study prioritization in a pandemic setting. METHODS: We performed semi-structured interviews with German stakeholders involved in clinical research during the COVID-19 pandemic. We continued sampling and thematic text analysis of interview transcripts until thematic saturation of challenges and potential response strategies was reached. RESULTS: We conducted 21 interviews with investigators, oversight bodies, funders and research support units. For the first topic informed consent we identified three main themes: consent challenges, impact of consent challenges on clinical research, and potential strategies for consent challenges. For the second topic prioritization of clinical studies, we identified two main themes: perceived benefit of prioritization and potential strategies for prioritization. All main themes are further specified with subthemes. A supplementary table provides original quotes from the interviews for all subthemes. DISCUSSION: Potential response strategies for challenges with informed consent and study prioritization partly share common ground. High quality procedures for study prioritization, for example, seem to be a core response strategy in dealing with informed consent challenges. Especially in a research environment with particularly high uncertainty regarding potential treatment effects and further limitations for valid informed consent should the selection of clinical trials be very well justified from a scientific, medical, and ethics viewpoint.

Should the governance of individual treatment attempts ("Individuelle Heilversuche") include praxis evaluation? Results from qualitative stakeholder interviews.

INTRODUCTION: Individual treatment attempts (ITAs) are a German concept for the treatment of individual patients by physicians with nonstandard therapeutic approaches. Due to the lack of evidence, ITAs come with a high amount of uncertainty regarding the risk-benefit ratio. Despite the high uncertainty, no prospective review and no systematic retrospective evaluation of ITAs are required in Germany. Our objective was to explore stakeholders' attitudes toward the retrospective evaluation (monitoring) or prospective evaluation (review) of ITAs. METHODS: We conducted a qualitative interview study among relevant stakeholder groups. We used the SWOT framework to represent the stakeholders' attitudes. We applied content analysis to the recorded and transcribed interviews in MAXQDA. RESULTS: Twenty interviewees participated and pointed to several arguments in favor of the retrospective evaluation of ITAs (e.g. knowledge gain about circumstances of ITAs). The interviewees expressed concerns regarding the validity and practical relevance of the evaluation results. The viewpoints on review addressed several contextual factors. CONCLUSION: The current situation with a complete lack of evaluation insufficiently reflects safety concerns. German health policy decision makers should be more explicit about where and why evaluation is needed. Prospective and retrospective evaluations should be piloted in areas of ITAs with a particularly high uncertainty.

Challenges and proposed solutions in making clinical research on COVID-19 ethical: a status quo analysis across German research ethics committees.

BACKGROUND: In the course of the COVID-19 pandemic, the biomedical research community's attempt to focus the attention on fighting COVID-19, led to several challenges within the field of research ethics. However, we know little about the practical relevance of these challenges for Research Ethics Committees (RECs). METHODS: We conducted a qualitative survey across all 52 German RECs on the challenges and potential solutions with reviewing proposals for COVID-19 studies. We de-identified the answers and applied thematic text analysis for the extraction and synthesis of challenges and potential solutions that we grouped under established principles for clinical research ethics. RESULTS: We received an overall response rate of 42%. The 22 responding RECs reported that they had assessed a total of 441 study proposals on COVID-19 until 21 April 2020. For the review of these proposals the RECs indicated a broad spectrum of challenges regarding (1) social value (e.g. lack of coordination), (2) scientific validity (e.g. provisional study planning), (3) favourable risk-benefit ratio (e.g. difficult benefit assessment), (4) informed consent (e.g. strict isolation measures), (5) independent review (e.g. lack of time), (6) fair selection of trial participants (e.g. inclusion of vulnerable groups), and (7) respect for study participants (e.g. data security). Mentioned solutions ranged from improved local/national coordination, over guidance on modified consent procedures, to priority setting across clinical studies. CONCLUSIONS: RECs are facing a broad spectrum of pressing challenges in reviewing COVID-19 studies. Some challenges for consent procedures are well known from research in intensive care settings but are further aggravated by infection measures. Other challenges such as reviewing several clinical studies at the same time that potentially compete for the recruitment of in-house COVID-19 patients are unique to the current situation. For some of the challenges the proposed solutions in our survey could relatively easy be translated into practice. Others need further conceptual and empirical research. Our findings together with the increasing body of literature on COVID-19 research ethics, and further stakeholder engagement should inform the development of hands-on guidance for researchers, funders, RECs, and further oversight bodies.