Embedding good clinical practice into investigator-initiated studies or trials.

Investigator-initiated studies/trials (IISs/IITs) help in generating data on effectiveness and safety of a drug in the real-world setting and attempt to answer questions that clinicians face in their day-to-day practice. Ensuring the accuracy and validity of collected data is routinely carried out by clinical trial monitors in industry-sponsored trials but is often lacking in IITs conducted in academia and private practice. Conducting IITs is not only important in understanding more about the disease area/drug action but can also be instrumental in translating academic research into product development. Deficiencies in the quality control of these trials can lead to inadequacies in data accuracy and validity that could lead to significant delays in bringing both accurate medical information and innovative therapies to patients in conditions with unmet medical needs in India (e.g., multidrug-resistant tuberculosis, dengue, and Kala-Azar). Figer et al. in this edition highlight the fact that there is rigorous monitoring to ensure adequate and accurate data documentation in Pharmaceutical Industry-sponsored studies, whereas in comparison, the IISs may not follow such quality checks.[1] The study that they report is from a single institution, but the results would be relatable to academic institutions and private practice across the country.

Data from medical centers outside India state that only about 65% of IITs reported are monitored, and hence, there is a clear need for training and education for investigators conducting IITs.[2] In the case of IITs conducted in the United States by Physician Investigators, they can very well expect that the USFDA may “periodically inspect trial sites” to ensure that all requirements are being met.[3] A review of the requirements for IIT funding approval by Pharmaceutical Industry shows that as a best practice once the IIT is approved, then investigator is expected to be trained on Adverse Event reporting and other aspects of Good Clinical Research Practice (regulatory authority and ethics committee approval, informed consent, listing the study on Clinical Trials Registry of India, etc.). The investigator is also expected to take the study all the way to publication. Unfortunately, the funding sponsor does not require that the investigators have to ensure data quality in the IIT that has been funded (based on the review of webpages of companies sponsoring IITs) nor do they apply the same rigor in ensuring that the investigator is trained on these critical trial-related activities that can impact patient safety. This is certainly a missed opportunity to embed Good Clinical Practice (GCP – ensuring ethics and data Quality) by default into an IIT.

The latest addendum to ICH GCP, E6(R2), discusses a need for quality management across the clinical trial lifecycle.[4] As individual investigators may not have resources to hire external monitors or auditors for an IIT, it may be good investment by the institution/hospital/group private practice to institute a quality assurance (QA) program to ensure the safety of clinical trials subjects, accuracy of data, compliance to regulatory requirements, and protocol compliance for therapeutic and nontherapeutic IITs.[5] Since protecting the safety and welfare of the subjects enrolled in IITs is paramount, conducting a risk assessment to prioritize the oversight that is required would then be a logical first step for the program. As part of this risk assessment, algorithms can identify those studies that pose the highest risk based on study characteristics (e.g., protocol complexity, study phase, study team experience, and other criteria). Risk mitigation can be accomplished by actively monitoring studies and consistently reviewing deviations/violations. When an issue is identified, the QA group can work diligently with the investigator(s) to emphasize the importance of root-cause analysis and corrective action plans. This active QA process can be instrumental in reducing the number of protocol deviations/violations, improving the data quality, and ensuring patient safety. A well-functioning QA program can be an integral part of the institution's research thrust area, providing essential support for the investigator-initiated clinical trials undertaken by investigators. If institutions recognize the importance of IITs as facilitating innovation/furthering medical research, providing investigators with the resources to effectively conduct their studies to further patient safety, and ensuring data quality will become top priorities. This will also enable a research ecosystem with credible data being generated by researchers in academia,[6] improve citation per article, lead to more patent filings, and support the avowed vision of the government bringing to the market a “made in India” drug molecule.[7]