Trial Planning & Design

Trial planning and design

Guidelines for Good Clinical Practice in Clinical Trials (1998)link to external site

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 baselink to external site to support the positive impact that PPI can have on participation recruitment and retention in clinical trials.  Many funders will require evidence of genuine involvementlink to external site 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 Frameworklink to external site (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 Researchlink to external site (NIHR), the process and criteria for inclusion of research on the NIHR Clinical Research Network Portfoliolink to external site and the importance of public and patient involvementlink to external site when conducting research.

The NIHR Research Design Service (RDS)link to external site 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)link to external site, which provides information on the infrastructure for research in the UK. Their web pages include information on Clinical Research Networklink to external site and Clinical Trial Units (CTUs)link to external site, 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 Networkslink to external site).

3) The critical path for undertaking a clinical trial can be complex. The RD Info Research Process Flow Chartlink to external site 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)link to external site is a source of practical support and guidance on the trial management process.

4)  The MRC HTMR Networklink to external site 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 Packlink to external site” 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 Trialslink to external site.

Core Outcome Measures for Trials

The COMET (Core Outcome Measures in Effectiveness Trials) Initiativelink to external site brings together people interested in the development and application of agreed standardised sets of outcomes, known as ‘core outcome setslink to external site’ (COS). These sets represent the minimum that should be measured and reported in all clinical trials of a specific condition, and are also suitable for use in clinical audit or research other than randomised trials.

The COMET database contains information on published and ongoing core outcome set studies, and is regularly updated. The COMET initiativelink to external site also supports workshops, presentations and meetings promoting the use of core outcome sets.

Further reading:

Lancet Series on Research Waste:

Other Toolkits available:

  • Data and Tissue Toolkitlink to external site: 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 Toolkitlink to external site: A regulatory tool for those conducting stem cell research in the UK.
  • Experimental Medicine Toolkitlink to external site: For investigators, R&D Managers and ethics committees involved in experimental medicine studies.

Further resources on Patient and Public Involvement: