An audit of institutional ethics committee queries raised after initial project submission by a single research department at a tertiary referral center in India.

Introduction: The institutional ethics committees (IECs) raise queries following protocol reviews. The quality of these queries would be a useful metric to assess how well the IEC executes its fundamental role of protecting participants. Methods: Queries received after the initial review and replies sent by a single research department were evaluated. A content analysis was done to identify the domains and categories of queries. We categorized these queries as administrative, ethics related, and scientific. The impact of each query in improving the science or safeguarding the rights and safety of research participants (ethics) was evaluated by two authors of this manuscript: one affiliated and the other nonaffiliated to the institute. Kappa statistics were used to evaluate for agreement between the two. Results: A total of 13 studies (investigator-initiated studies [IISs]: 7 and pharmaceutical industry-sponsored studies [PSSs]: 6) formed the final sample size for analysis. The total number of queries was 364 (IIS: 106 and PSS: 258; P < 0.001). With regard to the categories, we found n = 42 (11.54%) to be irrelevant at that stage of the review process; n = 51 (14.01%) were about information already available which the IEC had missed; n = 67 (18.41%) queries where the IEC needed paraphrasing; n = 50 (13.74%) were entirely relevant with the need for further clarification; and n = 154 (42.31%) had been missed by the investigator during the initial submission. The overall agreement between the affiliated and unaffiliated investigators was just 12.9% (P < 0.001). Conclusions: We found that approximately 25% of the queries raised by the IEC were redundant. It is our opinion that this redundancy could have been channeled into greater focus on scientific and ethical aspects of the protocol. Ongoing dialog between investigators and ethics committees may help address this. Perspectives between the affiliated and the unaffiliated investigators with regard to the relevance of queries were grossly different.

An audit of US FDA warning letters issued to sponsors, institutional review boards and investigators over a six-year period.

The present audit was carried out with the objective of evaluating warning letters (WLs) issued to trial sponsors, clinical investigators and institutional review boards (IRBs) by the United States Food and Drug Administration during a six-year period and compare it with two similar earlier audits. WLs were reviewed and classified as per stakeholders and further categorised as per predefined violation themes. The chi-square test was performed for trend analysis of WLs. A total of 62 WLs were issued to the three stakeholders. The maximum number of WLs were issued to the clinical investigators (36/62, 58.06%), followed by sponsors (19/62, 30.64%), and least to the IRBs (7/62, 11.29%). Among sponsors, lack of standard operating procedures for the monitoring, receipt, evaluation and reporting of post-marketing adverse drug events was the most common violation theme (8/19, 42.1%). Among clinical investigators, deviation from investigational plan was the most common violation theme (31/36, 86.11%.). For IRBs, inadequate documentation was the most common violation theme (6/7, 85.71%). We saw an overall reduction in the number of WLs issued to the stakeholders. Thus, we identified multiple areas on which each stakeholder should work for improvement.

Factors influencing recruitment and retention of participants in clinical studies conducted at a tertiary referral center: A five-year audit.

INTRODUCTION: A key determinant of the success of any study is the recruitment and subsequent retention of participants. Screen failure and dropouts impact both the scientific validity and financial viability of any study. We carried out this audit with the objective of evaluating the recruitment and retention of participants in clinical studies conducted over the last five years at our center. METHODS: Studies completed between 2014 and 2018 at our center were included. Screening ledgers and study trackers were hand searched for screen failures and dropouts. Four pre-identified predictors were evaluated - risk as per the classification of Indian Council of Medical Research 2017 Ethical Guideline, nature of funding, study design, and nature of participants. Association of the predictors with screen failures and dropouts was determined using crude odds ratios along with 95% confidence intervals. All analyses were done at 5% significance using Microsoft Excel 2016. RESULTS: A total of n = 19 completed studies had n = 2567 screened and n = 2442 enrolled participants with a screen failure and dropout rate of 5% and 4%, respectively. We found 59% screen failures due to abnormal laboratory values. The main reasons for dropouts were lost to follow-up 86 (88%). High-risk and interventional studies were the predictors for both screen failures and dropouts, but pharmaceutical industry-funded studies and healthy participants were predictors for only screen failures. CONCLUSION: Risk, funding, study design, and nature of participants are important to be considered while planning studies to minimize screen failures and dropouts.