Regulatory Compliance of Drug Safety Reporting in Clinical Trials Approved by the Pharmacy and Poisons Board of Kenya

Abstract

Background Drug safety reporting in clinical trial is a continuous activity that goes throughout a products life cycle. Drug safety reporting compliance in clinical trials is important in identifying participant’s safety concerns and protecting them from adverse events. Standards for drug safety reporting and managing adverse events in clinical trials are internationally accepted and have to be maintained during clinical trials. This study was conducted to establish if drug safety reporting in clinical trials complies with national and international guidelines. Objectives The study aimed to determine the compliance of drug safety reporting in clinical trials approved by the Pharmacy and Poisons Board of Kenya, with national and international clinical trials guidelines. Methods A retrospective cross-sectional study was conducted at Pharmacy and Poisons Board which is a regulatory body established under the Pharmacy and Poison’s Act CAP 244 to regulate clinical trials. Clinical trial protocols and reports of adverse events submitted to Pharmacy and Poisons Board of Kenya from 2013 to 2017 were reviewed. Information was abstracted from the files using a checklist to determine if the clinical trial protocol and safety reports conform to the requirements set out by Pharmacy and Poisons Board (PPB) and International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice guidelines (ICH-GCP). Data obtained was used to compute indicators that reflect the extent of compliance to regulatory requirements. Descriptive data analysis was done using STATA version 10 software. Results Out of the 69 clinical trial protocols analysed 63 (91.3%) were internationally sponsored trials compared to 6 (8.7%) that were locally sponsored trials. Twenty four clinical trial protocols were Phase I; Phase II were 23 while 22 were Phase III. A review of the clinical trial protocols showed that 37 (53.6%) had an explicit objective on drug safety evaluation. On safety reporting methods and pathways assessment; clinical trials protocols with provisions for safety reporting to local ethics research committee (ERC) were 69 (100%).Protocols that had provision for safety reporting to the sponsor were 53 (76.8%).Sixty (87.0%) protocols had provision for safety reporting to PPB. Protocols with provisions for sponsor to report to regulatory agencies outside Kenya were 42 (60.9%). Protocols that had a data collection tool with a case report form of reporting suspected unexpected serious adverse reactions (SUSARs) were 63 (94.0%). Out of the 28 safety reports reviewed with respect to completeness and causality, 20 (70.4%) of the safety reports were complete while 8 (29.6%) of the safety reports were not complete as the patient code, age or type of suspected unexpected serious adverse reactions/serious adverse events (SUSAR/SAE) was not stated. Drug safety reports with age included were 94.4%. The type of suspected unexpected serious adverse reactions/serious adverse events (SUSAR/SAE) was stated in 38.9% of the safety reports. The start date of adverse event was stated in 5.6% of the safety reports and end date was included in 38.9% of the safety reports. Causality was stated as probable in 4 (12.5%) of the drug safety reports. In relation to reporting timelines of serious adverse events (SAEs); 40 (58.8%) clinical trial protocols complied with PPB guidelines on reporting timelines to PPB of not later than twenty four hours. Fifty seven (82.4%) clinical trial protocols complied with PPB guidelines reporting timelines to sponsor of not later than twenty four hours. On description of reporting timelines of suspected unexpected serious adverse reactions (SUSARs); 6 (9.0%) clinical trial protocols complied with PPB guidelines of reporting timelines to sponsor of not later than seven calendar days with follow up reports within eight days. Measures taken by the sponsor to mitigate serious adverse events were hospitalisation in which 22 (78.6%) of the safety reports had their clinical trial participants hospitalised. For 26(37.5%) studies the sponsor formed a data and safety monitoring board (DSMB) to conduct an interim data analysis and review emergent safety issues. In one case (1.6%), the clinical trial was terminated early as the study objective had been achieved. Expedited reporting was done in 8 (11.6%) trials that showed a significant risk by the sponsor to the regulatory body. Conclusion The study identified gaps in drug safety reporting in clinical trials which different stakeholders can use to improve communication between themselves to ensure timely reporting of adverse events. There is need for a safety data base that will ensure safety reports are complete, quantification of adverse events and follow ups are done. There is need for the regulatory body to carry out more inspections of clinical trial sites to improve drug safety reporting.