CHALLENGES IN IMPLEMENTATION OF GCP GUIDELINES
Introduction:
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials. GCP ensures that data and reported results are credible and accurate, and that trial subjects' rights, integrity, and confidentiality are respected and protected. According to [ICH-GCP E6, R2], released in 2016 to encourage implementation of improved approaches for clinical-trial management, as per these changes in various sections, and new approaches in QMS and RBM systems with a focus on human subject protection and data integrity. E6R2 was amended to promote more efficient approaches to the clinical-trial process, from the planning of protocol to study conduct and reporting.
Historical-background:
Participants of the 1997 conference were representatives of authorities and pharmaceutical companies from Europe, Japan, the US, Australia, Canada, Nordic countries, and WHO. The clinical trials industry has expanded significantly since ICH-GCP E6(R1) was published in 1996, due to an increase in globalization, clinical research complexity, and technical capabilities, E6(R1) guideline was flexible and allowed sponsors to implement innovative approaches to ensure the quality of clinical trials. ICH E6 got modernized with additional recommendations so that it can better facilitate long-term implications for the quality of clinical trials.
Challenges in the implementation of GCP:
Regulatory and ethical issues:
According to CDSCO clinical trial approval and trial requires to be carried out by Schedule Y regulations and Indian GCP standards. The FDA and ICH internationally promoted the RBM-risk-based monitoring method, although it is uncertain whether CDSCO will adopt such an approach, multinational corporations conducting worldwide clinical trials and Indian companies creating new pharmaceuticals for export will be unsure whether to undertake centralized monitoring in Indian trials. Because Indian GCP does not enable RBM, a company that uses this approach and reduces the frequency of on-site monitoring faces the risk of breaking regulatory standards, as the continuous review is EC's responsibility.
Investigator site concerns:
Sponsor challenges:
Implementing ICH-E6(R2) requires significant changes in all areas - quality systems, SOPs, technology, and team training, and at all levels - organization, investigator, sites, CROs, and vendors. Effective centralized monitoring requires a competent team with appropriate skills, well-defined SOPs, and electronic technologies. RBM requires investments in validated electronic Systems like EDC, and electronic solutions for remote data access, such as cloud-based storage, fax machines, secure websites, web portals, direct access to site files, and electronic health records. QMS and RBM require the involvement of all functions, with special cross-functional responsibilities for data management, statistics, clinical trial monitoring, and medical and safety monitoring.
The scarcity of GCP-trained competent professionals poses a major challenge in the implementation of GCP guidelines.
Majority of hospitals in India are not equipped to meet the GCP guidelines' infrastructure requirements, and we lack a regulatory inspection system to monitor adherence and compliance with these guidelines.
GCP requires written standard operating procedures for IRB/IEC, but there are no standard guidelines on the content of ideal SOPs to ensure consistency across hospitals.
In India, the administration of ICD is a major challenge because the patient/legal representative has immense faith in the doctor and they insist on signing the document without even reading it or by reading it superficially.
Safety reporting is the joint responsibility of the investigator and sponsor to report all serious unexpected adverse events to regulatory bodies.
Storage, handling, and control of Investigational products are the major challenges in the implementation of GCP guidelines.
Trial agreements are based on the institutional practice where the research grant goes to a centralized research account, there is no incentive for the investor for investing extra time, effort, and intellectual capital.
Negative/prematurely terminated trials are rarely published which leads to a major threat to the validity of Evidence-based Medicine as one gets to know only the positive results.
Sponsors must raise awareness among ECs and regulators about the challenges, opportunities, and benefits of new quality management and RBM approaches, and proactively educate investigator sites about RBM and provide necessary resources. Sponsor teams will also require training in novel concepts like risk assessment and management, setting quality tolerance limits, electronic system validation, and analytical approach to monitoring. ICH-GCP harmonized standard provides public assurance that trial subjects' rights, safety, and well-being are protected and it minimizes exposure to investigational products, improves data quality, speeds up new drug marketing, and reduces the cost to sponsors and the public.
References:
1. Bhatt A. International Council for Harmonization E6(R2) addendum: Challenges of implementation. Perspect Clin Res. 2017 Oct-Dec;8(4):162-166. doi: 10.4103/pics.PICR_124_17. PMID: 29109932; PMCID: PMC5654214.
2. Vijayananthan A, Nawawi O. The importance of Good Clinical Practice guidelines and its role in clinical trials. Biomed Imaging Interv J. 2008 Jan;4(1):e5. doi: 10.2349/biij.4.1.e5. Epub 2008 Jan 1. PMID: 21614316; PMCID: PMC3097692.
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