Quality Management System in patient based clinical trials : Why?
Despite the numerous scientific, technological, and operational advances in R&D that would be expected to increase the efficiency and success of drug development, a significant number of clinical trials still fail to produce new, effective, and safe medicines. Approximately 70% of Phase II trials are unsuccessful.Although this percentage might seem high, failure of early-phase trials is expected to some extent, as these trials are “exploratory,” “proof of mechanism,” and “proof of concept” trials in patients.What is unexpected, however, is the percentage of “confirmatory” Phase III trials that fail - about 50%. Theoretically, if early-phase trials provide the necessary criteria for moving a drug program to Phase III testing, relatively few Phase III trials should fail; but that is not the case. Failure rate is still higher.
Major reasons for failure of trials include failure to demonstrate efficacy and safety, poor trial design, ineffective site selection, poor recruitment, insufficient investigator involvement, poor trial execution, patient burden and safety issues etc. This is where quality management system plays an important role.
So let’s begin with QMS. What is QMS? A QMS system is the crux of any quality and compliance process. An effective pharmaceutical quality management system (QMS) will help you develop a culture of quality, support data integrity, keep suppliers under control, and maintain overall compliance. In terms of project management, QMS plays major part in the success of the project. It is integrated part of project management and project manager is ultimately responsible for all the quality processes.
Unfortunately, we are still living in the age old notion of “QA department is responsible for quality”. We forget that, QA is one of the stakeholder of the project, it is the entire project team, who is responsible for quality work.
Scenario in early phase is still better with in-line quality control procedures and robust oversight with numerous third party monitoring visits and external audits. However, QMS in patient based clinical trials is still in infancy.
When I had started my career in clinical trials, very few Indian pharma companies had concept of involvement of quality assurance teams in clinical trials. Situation is still not very optimistic today. Concept of quality in late phase clinical trials is still restricted to conduct of site audits and study file audits in majority of Indian pharma companies and CROs. Involvement of quality team starts after planning is completed and execution has been started. QMS starts with conception of the project and ends with close out. It is not only review of documents by third party but building quality standards for each and every process starting with protocol development to inspection by regulatory agencies.
If one ponders on number of protocol deviations in the particular study, one can have a bird view of process quality. Increased number of USFDA 483s to various Indian sites and rejection of study data by EMEA for various submissions by Indian origin companies confirm the requirement of robust concepts of quality in system itself.
In drug development process (NDA or ANDA), duration and cost, both are highest for clinical development, still quality management systems are poor for GCP compliant processes compared to GLP or GMP compliant processes. First step of E6 (R2) came to existence before 2010 and final guidelines (step 4) are published in 2016, still there is no improvement in the situation. Section 5.0 of E6 (R2) stresses on quality management as responsibility of Sponsor, still majority of the sponsors do not have robust oversight systems. Majority of pharma managements perceives quality as an additional cost and neglect that domain, but in the same language of finance, cost of non-conformance is always higher and leads to losses.
Quality management system build up is the need for an hour and should be taken seriously for reducing failures and cost of development.