Good Practice Action 5: Ensuring the right team is in place

Ensure accountability, particularly from funders or sponsors, for robust, justified trial designs, supported by multidisciplinary teams and collaborative networks that include statistical expertise

Coordinated efforts and diverse practical expertise enable more rigorous, well-justified trial designs. Having accountability from the funder and/or sponsor helps to build assurance that informative design choices and team capabilities are both valued and well supported.

This drives the development of rigorous, well‑designed trials and ensures that teams have the capacity to deliver reliable, informative trials. Without this, studies risk being underpowered, poorly designed or misaligned with clinical needs, leading to wasted resources and exposing participants to unnecessary risks and burdens, with no clear expectation of scientific or social value from the resulting research.

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Trial teams and others should:

Building collaborative networks and bringing together diverse expertise (e.g. statistics, IT, clinical operations, financial aspects) to fulfil all needs of the trial is important. In circumstances where access to expertise is limited, it mustn’t be left out. For example, in low resource settings such as low or middle-income countries (LMICs) where infrastructure and trial expertise is limited (Muhe et al., 2025), and there is limited statistical expertise globally. In these cases, funders can support buy-in of expertise.

When global health clinical trials are undertaken, they are often done with insufficient funding to support sustained development of research infrastructure and human resources in the LMICs in which they are set. To maintain clinical trial research efforts in global health over the long term, the ability to sustain research infrastructure and human resources for local settings through consolidated and minimised single-use research activities related to trial planning and execution is crucial.” (Park et al., 2021)

Adaptive trials can be more complex, making resource for staff expertise and other costs more difficult to predict (see the below table, from Wason et al., 2022).

Resource required

Examples of reasons of additional resource

Trial manager time

More complex protocol development

More time to create patient information sheets

Complexity of design

Amendments

Additional or more frequent meetings

Data cleaning co-ordination for interim analysis

Increased site communication and training

Additional user testing of updated systems

Increased co-ordination (i.e. timing of drug supply)

Regulatory interactions

Contract negotiations

Statistician time

Simulations of design operating characteristics

Protocol development

(Interim) SAP development

Interim analysis

Trial Steering Committee/Data Monitoring Committee Report preparation

More complex final analyses

Additional “unblinded” statistician

Additional quality control statistician

Specification of system needs, user testing of systems

Data manager/programmer/information specialist time

Increased set-up resource to prepare for planned adaptations and to build more complex databases/randomisation systems

Increased time for complexity of data management plan

Data cleaning for interim analysis

Database lock for interim analyses

Database amendments due to adaptations

Staff with specialist expertise (e.g. senior statisticians/methodologists/trial manager)

Complexity of design

Expertise required in adaptive designs

Understanding consequences of adaptations

Intervention costs

Extended timelines, and costs for changes in drug manufacture due to an adaptation (e.g. dose changes)

Intervention-related data collection costs

Non-staff CTU costs

Training

Additional meeting costs

Regulatory agency fees for amendments

Additional travel costs if on-site monitoring is needed

License fees for specialist software

Other

Increase in timelines for adaptive designs due to planned breaks in recruitment due to interim analyses (not in all cases)

Increase in resource to handle uncertainty

Table 1.  Resources where adaptive designs increase use, from Wason et al., 2022, licenced by CC BY 4.0.

The Costing Adaptive Trials (CAT) project offers guidance for planning resources, including recommendations for funders to help resource innovative trial designs (Wason et al., 2022):

  1. Develop easily accessible funding schemes to cover the intensive development pre-funding work-up period
  2. Recognise adaptive designs as beneficial to research, and but not necessarily cheaper to run
  3. Understanding that some aspects are more resource-intensive than with traditional trials, particularly as units build their experience in running these trials
  4. Consider ways to allow more flexibility in specifying resources, including more space in application forms to describe how resources are impacted by adaptations, with multiple funding estimates
  5. Consider supporting more methodology research that could investigate reducing additional costs (Studies Within A Trial – SWAT)
  6. Introduce more funding for shared infrastructure (e.g., platform trial infrastructure and innovative design advice) for developing and efficiently delivering innovative trials
  7. Have more cross-panel and cross-funder opportunities for funding seamless trials and master protocols rather than operating in fixed phases of trials
  8. Consider appropriate funding mechanisms for dealing with cost changes due to adaptation
  9. Avoid financial penalties for the efficiency achieved in studies stopped early by allowing flexible use of the saved resources (e.g., to cover the cost for the development of subsequent investigations).

How funders can ensure this happens

  1. Ask research teams about their trial design and hold a structured review (see Good Practice Action 2)
  2. Ask research teams who is responsible for the statistical calculations of the trial; and what statistical methods will be used to compare groups for primary and secondary outcomes; and who will be included in each analysis (e.g. all randomised participants).
  3. Ask for a description and justification of how missing data will be handled.
  4. Ask about the wider team responsible for running the trial day-to-day including the people who will provide organisational support to trial sites.  Ask about the composition, roles and responsibilities of those tasked with day-to-day management, how often they will meet, and how trial progress is monitored, and correcting actions taken.
  5. Provide funding for buy-in to support trials where infrastructure or expertise is limited, e.g. in low-resource settings
  6. Example questions to ask are given in the INFORM Structured Grant Form, Questions {9, 22, 23 and 28}

 

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