Complex Innovative Design (CID) trials could potentially be transformed for the better, following the publication of recommendations, published today in the British Journal of Cancer.
The authors behind the recommendations, which include representatives from the Health Research Authority, believe, if implemented, the 10 recommendations developed for CID trials could ultimately reduce the time it takes to get innovative treatments to patients with cancer.
They are now calling on clinicians, funders, regulators and the pharmaceutical industry to get behind the recommendations and work together to rapidly implement them.
CID trials are increasingly being used as an evaluation method by researchers, instead of traditional drug development pathways involving clinical trials from phases 1 to 4.
The CID approach enables researchers to carry out more complex trials that address multiple clinical questions at once. For example, a drug can be simultaneously evaluated for safety and efficacy with different cancer types, which can change as the trial progresses, accelerating the traditional route to drug licencing.
However, they can be challenging to conduct and there are currently no practical guidelines for teams that fund, design and conduct these trials in Europe.
The Experimental Cancer Medicine Centre (ECMC) network, funded by Cancer
Research UK, the National Institute for Health Research (NIHR) and the health
departments in Scotland and Wales, convened a working group of academics,
funders, regulators, pharmaceutical industry representatives and patients to
address this challenge. Both HRA
Engagement Manager Will Navaie and
Research Ethics Committee Chair Stephanie Ellis took part in the working group and have blogged about their experiences.
The working group developed ten key recommendations to cover each stage of the clinical trial pathway.
Each recommendation covers a specific stage of the clinical trial pathway including: trial planning and design, protocol development, patients and public involvement, patient-facing documentation, statistical analysis, defining leadership and oversight, dissemination of results, staff training, the approval process, funding, and evaluating the impact on public health.
Taken together, these recommendations could improve the conduct, quality and acceptability of oncology CID trials in clinical research. Furthermore, improving how different stakeholders interact, promote and share their learnings from CID studies, say the authors, will foster a clinical research environment that could enable CID trials to be carried out in a range of new clinical areas.
Juliet Tizzard, Director of Policy at the Health Research Authority, said: “These important recommendations now bring clarity for researchers in terms of how they should be running high quality CID trials. They are a statement of intent for the UK as a global leader in conducting efficient and life-changing clinical research.”
Professor Pam Kearns, Director of the Cancer Research UK clinical trials unit at the University of Birmingham and co-author of the paper, said: “We owe it to our patients to bring potentially more effective novel treatments into the clinic as quickly as possible, and these recommendations will ensure we have good quality CID trials in place to deliver this promise.”
Dr Aoife Regan, Head of the ECMC programme office, said: “These recommendations show the power of the ECMC network as a convening force to help strengthen the position of the UK as a world leader in experimental cancer medicine. We hope these recommendations will have an impact not just for cancer research but for all complex trials across all disease types.”
Nick Lemoine, Medical Director at the NIHR, said: “Getting promising new cancer treatments to patients who need them the most can take some time, so speeding up this process through Complex Innovative Design trials is a priority. With the expertise within the ECMC network and the new guidelines in place, the UK is now one of the best equipped countries to deliver these trials, which represent the future for evaluating new cancer drugs.”
Debbie Keatley, patient representative and co-author of the guidelines, said: “Patients tell us that they need information about trials in an easy to understand format and language. They also want reassurance that the results seen in the trials will be applicable to real patients seen in the clinic. We welcome these guidelines, which put the patient first.”
The organisations who took part in the working group
The ECMC representatives were joined by:
- Health Research Authority (HRA),
- Medicines and Healthcare products Regulatory Agency (MHRA)
- National Institute of Health and Care Excellence (NICE)
- Association of the British Pharmaceutical Industry (ABPI)
- BioIndustry Association (BIA)
- Cancer Research UK (CRUK)
- Department of Health and Social Care
- Cardiff and Vale University Health Board
- NHS Greater Glasgow and Clyde, Clinical Trial Units
- Research Ethics Committees
- Academic institutions
- National Institute of Health Research (NIHR)
- Independent Cancer Patient Voices
- Researchers and NHS Trust Research and Development (R&D) Managers from across the UK.
The 10 recommendations
- Trial Planning and Design: Engagement with Regulators: Investigators/sponsors should arrange a joint meeting with regulators, HTA bodies and other key stakeholders as early as possible before or during the trial design to guide and shape the delivery of the CID trial, especially if accelerated (e.g. conditional) approval is likely to be applied for.
- Protocol Development: The protocol should identify and briefly describe any possible future modifications (such as additional study arms) to reduce the likelihood of substantial amendments. Events defining the end of trial must be included.
- Patients and public involvement (PPI): Patients and the public may require specific training, support, and perhaps also accreditation, in order to review and/or manage CID trials.
- Patient Facing Documentation: A practical approach using three-part patient information should be provided; comprising an invitation document, a study arm-specific document and a handbook. Multimedia can be considered for some or all of these documents.
- Statistical Considerations: Experienced and detailed statistical input is required to provide an over-arching statistical design with flexibility to incorporate individual variations for different treatments, diseases and molecular characteristics. Having a range of expertise within the oversight committee will ensure timely and appropriate responses to the frequent analyses produced.
- Defining Leadership and Oversight: A Trial Management Group with experience of CID trials should be convened to oversee the study. New Chief Investigators (CIs) and/or Principal Investigators (PIs) should be appointed during the study as its requirements evolve.
- Dissemination of Results: When a research question is answered, or a study arm is completed, timely reporting of trial data at these pre-specified time-points should be supported as best practice.
- Staff Training: Training in complex trial methodologies should be included in the undergraduate and post-graduate training curricula of relevant health care professionals in order to ensure appropriate resources are in place to deliver CID trials.
- Approval and Reimbursement Decisions: Accelerated access initiatives are vital in ensuring CID trial findings are rapidly transitioned to regulatory approval, reimbursement decisions and adoption into clinical practice.
- Evaluating the impact on public health: Impact analyses should be conducted on all CID trials to ensure they deliver on their promise to provide timely access to these medicines in clinical practice without compromising patient safety.