The best time to receive input from Clinical Operations professionals is during the protocol development stage. A feasibility assessment done in conjunction with protocol development better ensures a protocol is developed with the greatest chance to enroll subjects in accordance with timelines and expectations.
Many impediments can restrain a protocol from achieving its enrollment timelines. Foremost amongst these are protocol amendments. While protocol amendments can impart valuable and necessary process changes or study updates, they also cause delays due to inherent added regulatory review processes, study document editing and loss of momentum and commitment from investigators and their research staff.
ICH refers to the International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use. GCP refers to Good Clinical Practice. GCP is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are credible. The objective of ICH GCP Guidelines are to provide a unified standard for the European Union (EU), Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.
The guideline was developed with consideration of good clinical practices of the European Union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the World Health Organization (WHO).
ICH GCP should be followed when generating clinical trial data that are intended to be submitted to regulatory authorities.
FDA CFR refers to the Code of Federal Regulations published, maintained and updated by United States Food and Drug Administration (US FDA). When used in the clinical trial setting, (Title) 21 CFR is being referenced. There are 50 Titles of CFR; FDA CFR Title 21 regulates food and drugs manufactured or consumed in the United States, under the jurisdiction of the Food and Drug Administration (FDA), the Drug Enforcement Administration, and the Office of National Drug Control Policy.
21 CFR Part 11 refers to the regulations outlined in the U.S. Code of Federal Regulations, Title 21, Part 11. This establishes the ground rules for the technology systems that manage information used by organizations subject to FDA oversight. Any technology system that governs such GxP processes as Good Laboratory Practices (GLP), Good Clinical Practices (GCP), and Good Manufacturing Practices (GMP) also requires validation of its adherence to GxP.
21 CFR Part 11 sets requirements to ensure that electronic records and signatures are trustworthy, reliable, and generally equivalent substitutes for paper records and handwritten signatures. It also offers guidelines to improve the security of computer systems in FDA-regulated industries. Subject companies must prove that their processes and products work as they are designed to, and if these change they must revalidate that proof.
Foremost, we define the ultimate success by the advancement of medicine. With that definition, a safe and effective compound or product is needed as well as the funding to support its development. If those factors are evident, success for a clinical trial is defined by the study being consistently executed in accordance with the protocol, enrollment completed commensurate within established timelines and producing a dataset with quality sufficient to support a detailed analysis and evaluation of results.
That success is impacted most by three critical elements – Commitment, Quality and Efficiency. The greatest of these is commitment. Commitment refers to the retention of intellectual capital on a project (turnover of CRO monitors and managers) as well as the effort and focus an investigator and their research team gives to the protocol versus other protocols. Neozene historically retains 95% of its personnel throughout the duration of projects. A large volume CRO historically retains less than 25% of its personnel on an assigned project throughout the duration of an average 24-month project.
Foremost, it is important to use real time intelligence and assessments to validate historical knowledge and prior experience of potential investigators. Investigators and the ability of their research staff to commit to protocols vacillates tremendously influenced by myriad factors. Even if they have the capacity, Investigators and their research staff report a value for the experience of and relationships with the CRO monitors and managers they work with above their preference for evaluating an individual compound or product. Utilizing a CRO with historical personal experience and established personal relationships with investigators and their staff can be a critical driver to determining the commitment of investigators to your protocol. The typical large volume CRO monitor averages 3 years’ experience. All Neozene monitors have over 15 years’ experience.