Trial Planning & Design

Trial planning and design

Guidelines for Good Clinical Practice in Clinical Trials (1998).

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.

Successful trials often share similar characteristics. They are:

  • Conceptually simple and tailored to the patient group
  • Address questions of clinical relevance where genuine uncertainties exist
  • Avoid unnecessarily complex/restrictive entry criteria to ensure generalisability, where appropriate
  • Avoid unnecessarily complex data requirements (resulting from a careful justification of each data point to be collected)
  • Ensure the most appropriate choice of control arm (where appropriate)
  • Ensure robust allocation concealment (where possible)
  • Ensure robust blinding of intervention or appropriately blinded outcome assessments (where appropriate).

It is important to collaborate with a statistician who can help with:

  • Designing your trial
  • Choosing an appropriate outcome
  • Providing justification of the sample size
  • Advising on appropriate randomisation methodology
  • Drawing up a statistical analysis plan
  • Handling and structuring collected data
  • Preparing and presenting interim reports to Data Monitoring Committees (DMCs), if applicable.

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.

If you are planning extensive public involvement in your research, you might want to consider assessing the impact of this using a tool such as the Public Involvement Impact Assessment Framework (PiiAF).

The National Context:

When initiating a trial, researchers should familiarise themselves with the framework in place for conducting trials. In particular:

1) The role of the National Institute of Health Research (NIHR), the process and criteria for inclusion of research on the NIHR Clinical Research Network Portfolio and the importance of public and patient involvement when conducting research.

The NIHR Research Design Service (RDS) supports researchers in England to develop and design high quality research proposals for submission to NIHR and other national, peer-reviewed funding competitions for applied health or social care research (see Funding Proposal station).

2) The role of the UK Clinical Research Collaboration (UKCRC), which provides information on the infrastructure for research in the UK. Their web pages include information on Clinical Research Network and Clinical Trial Units (CTUs), including the process for identifying CTUs that may have expertise in coordinating multi-site research in different disease areas or with different trial designs (see UKCRC Registered CTU Networks).

3) The critical path for undertaking a clinical trial can be complex. The RD Info Research Process Flow Chart gives an overview of the process. The positioning of the stations on the route maps within this Toolkit also indicate which activities can be conducted in parallel and which activities should be completed before moving on the to the next stage.

For those new to managing trials, the NIHR Trial Managers Network (TMN) is a source of practical support and guidance on the trial management process.

4)  The MRC HTMR Network promotes and encourages collaborative methodological research relevant to trials, with the aim of accelerating implementation of the most effective and appropriate methods. It supports workshops, conference and training in trials methodology, in addition to acting as a resource to highlight events and courses across the UK. 
 
The MRC HTMR Network also collates outputs from various projects and initiatives under their “Guidance Pack” for trials. 

The Network and individual Hubs also offer assistance to colleagues based in Clinical Trials Units and the Research Design Service when they receive enquiries, through the Methodology Advisory Service for Trials.

Further reading:

Lancet Series on Research Waste:

Other Toolkits available:

  • Data and Tissue Toolkit: Practical help with the legislative and good practice requirements relating to the use of personal information and human tissue samples in healthcare research in the UK
  • Stem Cell Toolkit: A regulatory tool for those conducting stem cell research in the UK.
  • Experimental Medicine Toolkit: For investigators, R&D Managers and ethics committees involved in experimental medicine studies.

Further resources on Patient and Public Involvement: