Institutional Review Boards and post-approval monitoring (PAM) of human research: content analysis of select university (academic health center) web pages across the USA.

OBJECTIVE: To conduct a content analysis of IRB webpages of select universities (academic health centers) in the USA that describe post IRB- approval monitoring activities. METHOD: This was a qualitative study. Thematic analysis was the method to review the webpage content of selected academic health centers (AHC) within the USA. RESULTS: Some US academic health "centers" IRB administrative or research compliance offices conduct post- approval monitoring (PAM) of human subjects' research including clinical trials. The goals of this PAM programmes are to (a) ensure compliance to approved protocols, (b) preserve research integrity, (c) manage institutional risks, d) provide advisory/educational support to researchers, (e) recommend corrective actions for identified issues, and most importantly, (f) to protect the safety, rights, and well-being of research participants. Although not a requirement by law, the PAM program has legislative support in the US Code of Federal Regulations as part of the US Office for Human Research Protection's (OHRP) Federal Wide Assurance (FWA). This is especially for institutions that conduct studies funded by the Federal government. PAM on-site checks reveal various incidents of protocol deviations and violations. This includes issues with recruitment processes, informed consent discrepancies, and incidents of non-compliance. When a study protocol is identified as non-compliant, the principal investigator works with the PAM monitor to develop a corrective action plan that would allow the study to become compliant and avoid sanctions from the IRB or the regulatory authority. CONCLUSIONS: REC/IRB post-approval monitoring of clinical trials is a valuable mechanism of protection for research participants while giving educational and quality assurance support to researchers. The program enables early detection and resolution of non-compliance to approved protocols. The impact of the program in the USA requires further exploration.

Research ethics committees and post-approval activities: a qualitative study on the perspectives of European research ethics committee representatives.

OBJECTIVE: To explore the views of Research Ethics Committee (REC) representatives in the European Union (EU) on what the status quo is in terms of RECs' activities after the approval of trial protocols for clinical studies. METHOD: This is a qualitative study. The participants in this study are members or representatives of a research ethics committee from the member countries of the European Network of Research Ethics Committees (EUREC) and the United Kingdom. Thematic analysis was the method to assess interview transcripts. RESULTS: Interviews of REC representatives from 19 countries across Europe reveals that REC post-approval activities are predominantly limited to review and approval of protocol amendments. The majority of the RECs do not have mandatory continuing reviews or receipt of notifications of adverse events or protocol violations. In fact, most post-approval activities are the remit of the regulatory authorities. The interviewed members were also of the opinion that RECs in the EU do not have the legislative support, the organizational structure, the expert staff nor time to do active post approval follow-up. CONCLUSIONS: Post-approval follow-up activities for clinical studies by RECs is a valuable resource and means for early detection and resolution of protocol deviations and violations. However, a majority of RECs within Europe do not have active post-approval follow-up of approved protocols. The interviews revealed that resource challenges such as time, personnel, and organizational structure contribute to the lack of follow-up by RECs. Some RECs in the represented countries do not identify post-approval follow-up as part of their mandate but instead place emphasis on the culture of trust between the RECs and researchers. Current EU Regulations do not directly address the role of the REC after the approval of clinical trials.

The role of research ethics committees after the approval of clinical trial protocols in the EU and the USA: a descriptive content analysis of international and regional normative documents.

AIM: To conduct a descriptive content analysis of normative documents on the role of research ethics committees (RECs) after the approval of clinical trial protocols. The question to be addressed is whether and to what extent normative documents support a monitoring role for RECs in the United States and the European Union. DESIGN: A qualitative content analysis of 19 normative documents on clinical research as outlined by the International Compilation of Human Research Standards 2020 edition and other related documents for the EU and USA. RESULTS: After the approval of research protocols, RECs' general role is to receive reports from researchers on the trials' progress. Additionally, RECs receive notifications of protocol amendments, deviations and, to a lesser extent, violations, which is the remit of the regulatory/competent authorities. RECs are expected to issue opinions on clinical trials' progress and give supplemental opinions/approval or withdraw/suspend/terminate previous favorable opinions on adverse events or safety concerns that may arise. RECs are to receive an end of the trial report. CONCLUSION: The role of RECs post approval of protocols is to protect human participants through activities such as continuing review of: (a) progress reports, (b) notifications of significant protocol amendments, (c) adverse events, (d) protocol deviations, and (e) protocol violations. Although some international guidelines such as the Declaration of Helsinki emphasize the right to monitor, RECs' predominant activity is document review. In the USA, RECs are authorized to issue approvals and terminate/suspend previously issued approvals. However, in the EU, the approach is to relegate to member states to decide the extent of legislative power they wish to give to the RECs. The REC's opinion on the end of trial report is identified as an area for further exploration.

Back to WHAT? The role of research ethics in pandemic times.

The Covid-19 pandemic creates an unprecedented threatening situation worldwide with an urgent need for critical reflection and new knowledge production, but also a need for imminent action despite prevailing knowledge gaps and multilevel uncertainty. With regard to the role of research ethics in these pandemic times some argue in favor of exceptionalism, others, including the authors of this paper, emphasize the urgent need to remain committed to core ethical principles and fundamental human rights obligations all reflected in research regulations and guidelines carefully crafted over time. In this paper we disentangle some of the arguments put forward in the ongoing debate about Covid-19 human challenge studies (CHIs) and the concomitant role of health-related research ethics in pandemic times. We suggest it might be helpful to think through a lens differentiating between risk, strict uncertainty and ignorance. We provide some examples of lessons learned by harm done in the name of research in the past and discuss the relevance of this legacy in the current situation.

To dispense or not to dispense: Lessons to be learnt from ethical challenges faced by pharmacists in the COVID-19 pandemic.

The year 2020 is facing one of the worst public health situations in decades. The world is experiencing a pandemic that has triggered significant challenges to healthcare systems in both high and low-middle income countries (LMICs). Government policymakers and healthcare personnel are experiencing real-life ethical dilemmas and are pressed to respond to these situations. Many possible treatments are being investigated, one of which is the use of hydroxychloroquine or chloroquine. These drugs are approved for use by patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, and malaria. The demand for these products has increased, and the stocks are depleting for the patient population for whom the drugs are intended initially. Although both innovator and generic pharmaceutical manufacturers are making plans for increased production, there are challenges with global supply chains disruption and the retention of supplies for local markets. This may cause countries that rely on the importation of pharmaceuticals to be out of stock of supplies for an extended period. There are allegations of off-label prescribing and hoarding. Pharmacists are the custodians and dispensers of medications and are faced with the task of assessing prescriptions and making decisions about the allocation of these products. This paper seeks to 1) highlight some of the ethical challenges of dispensing hydroxychloroquine by pharmacists during the COVID-19 pandemic, 2) identify some of the responses to these issues from various regulatory authorities in the USA, and 3) recommend approaches to assist pharmacists in their decision-making process, especially in LMICs.