An inquiry by the Singapore Ministry of Health (MOH) has revealed ethical lapses in a research study conducted by the National Neuroscience Institute (NNI). The investigation, initiated in response to concerns raised by neurologists and patients, focused on a study examining the genetic structure of neurological diseases and medication response. The study aimed to recruit 1,500 subjects for each of the conditions: epilepsy, Parkinson's Disease and stroke, and 1000 for tardive dyskinesia.
Allegations and Investigation
The allegations against the study included patient recruitment without the knowledge of their attending physicians and failure to obtain informed consent, particularly for Parkinson's Disease (PD) patients undergoing L-dopa challenges and video recording. The MOH appointed a Committee of Inquiry to investigate these lapses in the ethics approval process and study conduct.
The committee reviewed study protocols, patient records, and interviewed researchers, doctors, and patients. Their investigation revealed several key areas of concern.
Key Issues Identified
- Ethics Approval Process: The research protocol submitted to Hospital Ethics Committees (HECs) lacked sufficient details on patient recruitment and procedures like 'on-off' observation and video-taping. HECs approved the study without seeking adequate clarification. Modifications to the PD study protocol were not submitted for ethics approval before implementation.
- Medical Confidentiality: Patients were contacted without informing their attending physicians. While the research team complied with existing hospital rules for accessing patient medical information, custodianship of patient medical information and procedures for its release were not clearly defined in some hospitals.
- Conduct of the Study: Written informed consent was not obtained for 'on-off' observation and video-taping. Patients' treatment regimens were modified without consulting their attending physicians, raising concerns about patient safety.
- Administration and Organization of the Study: The study, involving multiple principal investigators (PIs), disease conditions, and study sites, lacked formalized roles and responsibilities for team members. Regular coordination meetings were not held initially.
Recommendations for Improvement
The committee made several recommendations to strengthen the ethical approval and oversight of clinical research studies:
- Every institution conducting medical research should have a robust and effective HEC, supported by adequate administrative staff.
- HECs should not be overburdened with a workload that compromises the quality of ethics review.
- HECs should ensure studies are scientifically sound and review patient recruitment methodology, consent forms, and patient information sheets thoroughly.
- Hospitals should clearly define custodians of patient medical information and establish systems to inform attending doctors before releasing patient information.
- PIs and researchers should inform attending physicians of study subject participation, especially in studies with significant clinical interaction.
- Consent forms should be comprehensive yet easy to understand, with copies provided to study subjects.
- Any modifications to treatment regimens or procedures should be reflected in the study protocol and consent form.
- Research teams should hold regular meetings, and all researchers should be informed about local standards and guidelines concerning clinical research.
Impact and Future Directions
The findings of this inquiry highlight the critical importance of ethical oversight in clinical research. The recommendations aim to enhance transparency, protect patient rights, and ensure the responsible conduct of medical research in Singapore. Implementation of these recommendations is expected to improve the quality and integrity of future clinical studies.
