Clinical Trial Plan Development
The clinical trial is an experiment planned and aimed at testing a hypothesis. The hypothesis usually concerns the efficacy of a given intervention regarding any symptom, event or impaired characteristic of life in patients with any specific condition and a particular profile (e.g., male, female or both).
In order to get the best chances to perform a trial to detect the expected effect of the treatment, it should have not only pharmacological power (i.e., the appropriate dose) but also sufficient statistical power as well as the design power (i.e., the most appropriate design).
The sturdy trial design is essential to ensure a successful outcome. The trial design should be considered and made well before developing the protocol. This will help to make sure that all necessary practical requirements are identified early so that adequate funds can be requested.
A well-documented trial plan will facilitate the ethics committee, the process of developing funding applications, and R&D approvals/ permissions, and any other necessary regulatory approvals.
Successful clinical trial development plans should:
- Give clarity to the patient group and be conceptually simple;
- Label and address questions related to clinical trials where possible uncertainties exist;
- Abstain unnecessarily restrictive entry criteria and complex data requirements to ensure generalisability;
- Make sure the most feasible choice of a control arm, wherever required;
- Confirm robust allocation concealment (where possible);
- Ensure appropriately blinded outcome assessments.
Patient and public involvement (PPI) is necessary to ensure that the question proposed is relevant and significant to the people it directly affects and that the trial is worthy, feasible and practical. There is proof that supports the positive impact that PPI can have retention in clinical trials and on participation recruitment. Many funders will need as a condition of funding.
When initiating a trial, researchers should familiarize themselves with the framework in place for conducting trials.
The SOP should be formed by collaborating with people who can help with:
- Designing and planning the trial
- Choosing a possible outcome
- Giving justification of the sample size and its requirement
- Suggesting an appropriate randomization methodology for proper functioning
- Preparing and presenting reports to data monitoring committees, if required
Committees and centers during the clinical trial
The organization of the trial is decided. In rather large trials, and at least in all multicentre trials, it is the minimum in order to meet all the difficulties and solve all the problems. However, before deciding and appointing the Committees and Centers their head, the future principal investigator or the sponsor should set up a small meeting with colleagues and at least a statistician and tell them about the to-go plans. The committees should include:
- A steering committee, also known as the policy board which makes all the critical concerning decisions
- A sponsor who would be the funding body for the trial and can possibly be independent of active participation.
- Coordinating and data center having duties including management of day to day study, data collection, detect end points of each result, and even to perform statistical analysis
- The endpoint validation committee which works blindly in categorizing each endpoint of each experiment during the trial
- The data safety and efficacy committee which communicates with the policy board depending on the treatment results, provide the report.
The statistical power of a trial is a probability, which indicates the chance that the expected difference which could be detected at a specific level of statistical significance. In most cases, it is not advised to set the power below 0.85. The higher the power, the larger is the needed sample size.
The availability of effective treatments such as fibrinolytic, aspirin, beta-blockers, angiotensin converting enzyme inhibitors for myocardial infarction makes it more difficult to launch any new mortality studies.
Nowadays, most clinical trials are performed to explain and prove the superiority of some kind of treatment over another. As more effective treatments start being available, definite clinically significant improvements in an extensive clinical result are less likely to be obtained with any new treatments. The main interest for developing these treatments may not be major clinical events but superiority for secondary; however, essential features such as side-effects, quality of life, treatment practicability or cost are always kept as a priority. However, such criteria are only legible if the new treatment is at least as effective or more effective as the previous treatment on significant clinical results.
Therefore, a trial should be designed to show ‘equal efficacy’ on significant clinical outcomes and benefit on some other outcomes. A non- statistically significant result of a clinical trial does not imply equality of the efficacy of the tested treatments.
Three essential requirements for an unbiased database:
- To ensure without any glitch that all randomized patients are accounted for, in their original group in the analysis. Choosing an easy, simple to measure and acceptable definition of outcome is the easiest and preliminary action in order to fulfill this requirement.
- To obtain an unbiased and standardized classification of outcomes or measurements, a central assessment, events for the analysis of a trial and validation by a lab or committee blinded to treatment allocation is compulsory.
- To ensure the management of patients at the time of follow-up, including extra protocol diagnostic procedures within the compliance with study treatment, concomitant treatments, adverse events and notification of respective outcomes are not systematically influenced by the insight of the nature of the respective study treatment.
Before the planning of the study, there may be a possibility that the presently collected data is enough to show the supremacy or changes in comparison to the previous data or treatments. For moral reasons, it would not be correct without the planned ending. The data monitoring can never be changed or altered at the time of the course of study if suddenly the investigators have doubts regarding the safety or efficacy of the treatment. The complete process should be planned beforehand and described in the protocol.
Planning a clinical trial is a hard job. It requires expertise at a number of critical steps. It needs a team of very sensible and dedicated people because it is the primary requirement for a successful trial.