A robust trial design is essential to ensure a successful outcome. The trial design should be considered before developing the protocol. This will help ensure that all necessary practical requirements are identified early so that adequate funds are requested. A well-documented study plan will facilitate the process of developing funding applications, ethics committee and R&D approvals / NHS permissions, and any necessary regulatory approvals. While designing study and developing a Protocol, answers to research questions such as the rationale for the study, the main objectives (outcomes), the design and organisation (study management and oversight), statistical considerations, methodology, safety and risk management procedures, and plans for publication at the end of the study should be described. Patient and public involvement (PPI) is important to ensure that the question proposed is important and relevant to the people it directly affects and that the trial is practical and feasible. There is now a growing evidence base to support the positive impact that PPI can have on participation recruitment and retention in clinical trials. Many funders will require evidence of genuine involvement as a condition of funding.
The protocol should be as detailed as possible enabling the reviewing bodies to understand the study and for local investigators to follow step by step instructions to ensure adherence. It should be identified on the cover by the study title, the unique sponsor’s protocol reference number, and other relevant unique identifiers/registration references and the date and version number.
The Chief Investigator should retain all drafts copies of the protocol, work-ups with any comments as well as all subsequent approved versions for the Study/Trial Master File. In today's highly competitive environment, it is essential to gain as much information as fast as possible from early phase clinical studies to make decisions quickly with confidence. Study designs that reduce time from First-in-Human to clinical proof-of-concept maximize the amount of information gathered from one study and reduces overall costs, without jeopardizing the integrity of primary and secondary objectives.
Design and development process with fast turnaround times while addressing any possible challenges should meet all GCP/ICH guidelines. Medical officers, bio-statisticians and medical writers all should work as a team during this development process to ensure that a study's final outcome reflects clearly understood objectives.
This collaborative process means that any product approvals and market acceptance can be optimized from the start. In this way, you can avoid costly and time-consuming delays and pitfalls along the way.
During study design, it’s critical to optimize protocol design and global placement to achieve predictable delivery and avoid amendments that slow the process. After all, 55% of trial delays happen at the site level, which can have a cascade effect downstream. In order to achieve this one should be able to combine historical and feasibility data from individual sites with knowhow of typical roadblocks, such as varying standards of care, to provide better predictability. Incorporation of risk mitigation and contingency plans to ensure that trials meet milestones and budget. A consistent approach be adopted for site selection that steers away from underperformers.
Various study design challenges across a wide variety of designs include, among others first in human, novel drug therapies, first-in-class, efficacy, safety, non-inferiority, pharmacokinetic and pivotal trials. Trial Design Services Include: Selection of the patient population; Stratification based on biomarkers or other prognostic/predictive features; Treatment allocation methods (balanced, unbalanced, adaptive, minimization, permuted blocks, etc); Choice of efficient and reliable endpoints, as well as validation of surrogate endpoints; Sample size calculation; Trial simulations; Adaptive trial set-up; Scales to measure and standardize treatment benefits or harm; Factorial and cross-over designs for selected situations; Statistical analysis using of state-of-the art and novel methods; Interim analysis; regulatory authorization to discuss the study design or to defend the study results.