Food and Drug Administration (FDA's) Risk based approach guidance document helps clinical investigation sponsors to develop monitoring plans and strategies that are risk-based for medical products’ investigational studies, including biological and human drug products and medical devices. This guidance’s overarching goal is to promote protection of the human subject and clinical trial data quality through focusing the sponsor oversight on the most essential matters of reporting and study conduct . On the other hand, European Medicines Agency’s (EMA's) reflection paper on risk based approach to quality management is a document that helps clinical investigation sponsors to design, conduct, perform, monitor, audit, analyze and report clinical trials. Its overarching goal is to provide assurance that the safety, rights and well-being of the subjects of trial are well protected and ensure credibility of the clinical trials’ results. It guides in implementation of procedures that are necessary in securing the quality of the trial’s aspects .
The main similarity between these documents is that both aim at promoting the protection of the human subject as well as clinical trial data quality. The two documents contain enhanced details in turn providing an understanding of the expectations of the constitution of suitable validation efforts. They also acknowledge and provide a scope to the emerging processing technologies to help the validation effort. Both documents have significant stress on continued verification process via analysis of data to generate confidence in an ongoing suitable process. They also involve validation processes of quality risk assessment as well as proficient practices of quality systems.
The documents have a number of differences. The FDA guidance places more emphasis on documentation at the product development phase. This is done as part of validation of the process . On the other hand, EMA guidance encourages the product development activities use and it is less prescriptive on the requirements . There is also a difference in the number of batches that are required for the successful process validation before marketing. EMA guidance suggests a minimum of three batches fully backed with justifications . FDA, on the other hand suggests that the number of batches should be sufficient in order to provide confidence on the process . This is a subtle but significant difference between the two documents. EMA guidance is written to guide what is to be considered when developing strategy for process validation for dossier submission. Conversely, FDA guidance is written to help in developing and executing activities of process validation.
It is imperative to note that taking risk-based approaches do not involve taking short-cuts. The Risk-based approach is systematic and involves identification of risks continuously for all the activities that bear risks when designing, conducting and evaluating clinical trials. These trials are mainly based on ongoing emerging information on investigational medicinal products as well as the organization and systems of the collaborators and sponsors. To initiate this approach, it is instructive to appreciate the priorities to be monitored for a given system. It is also important to have knowledge of the nature of the systems that should be employed and understand the entire project as well as its objectives .
The approach involves taking into account the impact of the priorities on the trial subjects’ protection, the scientific objectives of the trial and assessing the data credibility during identification of the risks. It involves considering the trial development phase: methodology and trial design; trial conduct with recruitment and treatment of the subject; evaluation and reporting of data. It involves ensuring that expectations and processes for keeping site record, entry of data and reporting are clearly defined. It also facilitates a timely access to supporting documentation and clinical trial data. A risk-based approach should ideally be planned at the beginning of a clinical program then adapted protocol throughout the clinical development, building on gained experience with each study as well as regulatory, general advances made within the involved time period. A risk based approach involves periodic interaction in addition to discussion of approaches that are taken between the regulators and sponsors involved in supervision, authorization of clinical trial and the process of marketing authorization. Specific considerations with regard to the trial authorization and supervision must be made using the same risk management and prioritization techniques .
It is possible to have higher quality data by taking a targeted approach to data review as opposed to implementing the 100% review strategy. This is mainly because risk-based monitoring approaches, targeted on the risks to critical data processes and elements essential in achieving objectives of a study, are more likely to ensure protection of the subject and overall quality of the study than 100 % data review strategy and routine visits to clinical sites. For instance, incorporation of monitoring practices that are targeted to data review, where appropriate, improves the ability of a sponsor to ensure high quality of the clinical trial data. Several publications also suggest that various data anomalies including data fabrication, non-random data distributions and fraud, are more readily detected by centralized techniques of monitoring than by on-site techniques of monitoring .
European Medicines Agency. "Science Medicines Health." European Medicines Agency (2011): 3-11.
U.S. Department of Health and Human Services. "Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring." Guidance for Industry (2013): 1-22.