In recent years clinical trials have developed to provide greater benefits to both researchers and those people who participate in clinical trials.
The innovations in trial design allow for greater flexibility in the way trials are conducted. It might not be obvious how little flexibility there was in the previous designs, so we have prepared this information sheet to explain why these new designs might be useful.
One example is an adaptive trial design. The trial itself can be updated and even changed whilst the trial is in progress. This is quite different from traditional trial designs which allow for no changes at all whilst the study is in progress. In traditional trial designs everything is set in stone before the first patient commences in the study and no changes or adaptations are permitted.
Adaptive trial designs have revolutionised clinical trials.
What is an Adaptive Trial?
An adaptive trial uses information collected during the trial to change how to run the trial as it progresses. “Information collected during the trial” includes measures of how the participants are responding to the treatment, and even the effect of the treatment, whether in all participants or in certain groups of participants. Changes to how the study is run are called adaptations, and they occur in response to periodic reviews of the information collected during the trial, or sometimes also reviews of information outside of the trial, such as the results of other trials. The instructions about what changes are allowed and when changes can be made are written into in the study protocol. The study protocol is the document that describes the nature of the drug or treatment that is being studied and what questions the study is trying to answer. The protocol also prescribes the “rules’ for how the study will be conducted and how the trial information will be collected and analysed
What are Adaptive Platform Trials?
Platform trials allow the researcher to evaluate and compare multiple treatments at the same time. An adaptive platform trial (APT) is a platform trial that allows for planned modifications to one or more aspects of the trial whilst the trial is in progress.
APTs allow the trial to adapt in response to information that was not available when the trial began. This might mean the trial “learns” from the experience of earlier participants in the same trial.
In an adaptive platform trial, a single master or main protocol provides the overall structure of the trial. Then each different treatment group has its own set of rules described in mini protocols specific for each different treatment being offered.
How does an Adaptive Platform Trial differ from the traditional model?
Traditional clinical trials are the most common approach to generate evidence regarding the benefits and harms of potential medical therapies. They are considered to be well understood. However, they can be slow, inefficient, and limited in the questions they address, and there is evidence they are not as well understood as we might think.
This traditional model requires all key trial conditions to remain constant for the duration of the trial.
The design, treatment and number of participants is all fixed before the trial starts. Only when the study is completed (this may take a few years) is the data reviewed to see if the trial has answered the question that was proposed in the first instance.
The traditional model offers limited opportunity to assess the treatment throughout the study (except for safety reporting) and therefore offers little flexibility to adapt during the trial.
Key Features of an Adaptive Platform Trial
- Has a single “master” or overarching protocol with one or more small sub-studies. Each sub study is defined in a mini protocol but under the overall guidance of the master protocol (The Adaptive Platform Trials Coalition, 2019)
- May have any number of sub studies or subgroups within the trial with each subgroup receiving a different treatment.
- In each subgroup the number of participants required to evaluate if a treatment is working (or not) can change.
- Has predefined rules that permit the trial to be adapted as it is being conducted. These rules are designed around complex statistical models.
- Allows for regular review and analysis of the trial data at predetermined time points during the trial.
- Analysis of the data as it accrues allows for decisions to be made on the treatment given to participants.
- Treatments can be added or removed based on the scheduled analyses of the trial data.
- Changes can be made to the trial around the number of participants required, how different treatments are allocated, added or dropped and changes to the strength or frequency of doses of the drug being investigated.
The Pros of Adaptive Platform Designs
- The right number of trial participants can be included, no more and no fewer.
- May result in reduced participant numbers in a trial, reduced cost and time compared with traditional trial designs, while still making confident and trustworthy conclusions about the effect of trial interventions.
- Enables multiple research questions to be addressed at the same time.
- Allows researchers to drop treatments that do not improve outcomes, show poor tolerance or high toxicity.
- Potential to allocate participants to better treatments whilst the study is in progress.
New treatments can be added to the study as they become available.
Schematic of different trial designs
Traditional Trial
Adaptive Platform Trial
Video resources on Adaptive Platform Design for consumers
Adaptive Health Intelligence Website and ACTA Website
What is an Adaptive Clinical trial/ Tom Snelling
What are the Benefits of Adaptive Clinical Trials? Steve Webb & Tom Snelling
References
Increasing awareness and understanding of adaptive platform trials- K Lee et al. Poster Presentation, ACTA Annual Scientific Meeting, November 2022
Consumer involvement in Adaptive Trial Design
Models of Participation
Experience Based Co-Design
Experience-based co-design (EBCD) is a participatory design approach used in health research that involves the active engagement of end users, such as patients, caregivers, and healthcare providers, in the design and development process of health interventions, programs, or technologies. The aim of EBCD is to ensure that the needs, preferences, and experiences of the intended users inform and shape the final product, in order to make it more relevant, effective, and user-friendly.
In EBCD, end users are involved in the research process from the outset and throughout, participating in activities such as focus groups, interviews, observation studies, prototyping sessions, and user testing. Their feedback is used to iteratively improve the design and fine-tune the details of the final product. By bringing together the perspectives and expertise of end users, healthcare providers, and researchers, EBCD aims to create solutions that better meet the real-world needs and priorities of patients and healthcare providers.
Overarching Principles of EBCD1
Start participation as early as possible
Determine the most appropriate level of consumer and community member participation
Be clear and articulate about what is to be achieved to ensure consultation adds value to the research project.
Consider issues of ethics, confidentiality and bias.
Consumer advocacy is about providing a forum and voice to express differences of perspective
1 Adapted from Experience Based Co-Design Toolkit | Australian Healthcare & Hospitals Association (ahha.asn.au)
Consumer involvement in adaptive trial design
| Model | Details |
| Community or group meetings | Face to face meetings +/- teleconference facilities The method of consumer and community participation will influence the number of people who participate in the research project; ideally there will always be at least two consumers and community members involved. Requires Plain language statement/summary of the project Terms of Reference |
| Reference Groups | A reference group is a group of consumers and community members that can be referred to by researchers throughout the research. Reference groups are sometimes referred to as a Reference Panel Researchers will work with consumers and community members to decide what is the right number of people for a reference group. This will often depend on the size and topic of the research project, so it is important to make sure that there are enough members to generate a wide range of ideas and perspectives |
| Steering Groups | A group of stakeholders who steer and influence the research project, these members have more involvement with the direction of the research. This is high level participation. A steering group may be referred to as a steering panel. Groups can consist of any or all these stakeholders. • Researchers. • Clinicians, policy makers, health administrators. • Consumers and community members. • Members of consumer advocacy organisations and/or nongovernment organisations. |
| Consumer & Community Advisory Panels/Councils | Councils are a formalised group of people brought together to support the development of partnerships between consumers, community members, researchers and research organisations. A council’s purpose is to enhance the quality and relevance of research through consumer and community participation. They may be set up for a research organisation or a University faculty to provide input at a strategic level. They would not be established for individual projects and would not be relevant to individual trial design. |
| Consumer and Community Researchers | Consumers and community members who have been trained to work with researchers to conduct research. This is high level involvement. Consumer and community researchers can: • Have input into the development of methodologies. • Carry out interviews with other consumers and community members. • Co-facilitate focus groups. • Analyse results of interviews. • Go through consenting procedure (training is essential for this). |
| Writing or Commenting on Documents | Consumers and community members could help with writing or commenting on: • Information sheets and consent forms. • Pamphlets and brochures. • Plain language summaries. • Reports. • Documents about the dissemination of research results. |
Adapted from: McKenzie, A., Alpers, K., Heyworth, J. et al. Consumer and community involvement in health and medical research: evaluation by online survey of Australian training workshops for researchers. Res Involv Engagem 2, 16 (2016). https://doi.org/10.1186/s40900-016-0030-2. Available at: the-green-book-mar08.pdf (telethonkids.org.au)
Consumer Involvement in Research
Web based resources (not specific to Adaptive Platform Trials)
ACTA/CT:IQ
Consumer Involvement & Engagement Toolkit
AccessCR
Consumer Involvement Resources – AccessCR
Adaptive Health Intelligence Website
What is an Adaptive Clinical trial/ Tom Snelling
What are the Benefits of Adaptive Clinical Trials? Steve Webb & Tom Snelling
Australian Health Research Alliance
Consumer and Community Initative (CCI)
1. Development of a handbook with practical steps to guide stakeholders and organisations in embedding CCI in health and medical research-“Involving Consumers in Health and Medical Research-A practical handbook for organisations, researchers, consumers and funders”.
(Lead: Western Australian Health Translation Network)
2. Establishing a knowledge hub that brings ideas, knowledge, tools, research and activities together in a central online space. The aim of the National Knowledge Hub for Consumer and Community Involvement project was to explore the needs of consumers, clinicians, researchers and health service managers regarding CCI training and resources and access to these, and to use this information to develop a model for a national platform to meet these needs.
(Lead: Monash Partners, SPHERE)
3. Evaluating Impact-Identifying and testing approaches that show if involving consumers in health research makes a difference, and the kinds of effects it has in different research settings.