The Ins and Outs of Clinical Trials

by Andrew Webster and Ruchi Higham

The REGenableMED project was able to include a very detailed study of the clinical trials process through the linked work of Ruchi Higham, who has undertaken a doctoral thesis involving an in-depth study of trial design and its challenges. Fieldwork in the UK with cell therapy trialists and access to an actual trial process enabled Ruchi to build a wide-ranging and rich understanding of the world of the trial.

Developing cell therapies carries complex scientific and clinical uncertainties, which relate to both standardising and controlling tissue (a cell line known to be stable and to be of high quality) and delivery of that tissue via a treatment modality which typically has to be near-patient in practice. In this context, although cell therapies are regulated as medicines, from a trials perspective they have more in common with complex interventions such as surgical procedures. This creates obstacles that have impeded innovation. What we know from studying trials in depth is that the day- to- day challenges experienced are logistical and locally-contingent in nature, and in particular relate to the length of time in it takes to undertake a trial, the logistics and unpredictability of working with cells, problems with funding for trials and reimbursement for the treatment, and the number of different professional domains that must work together effectively for the trial to work.

However there are a number of actions that can be taken to address these issues, whilst also continuing to ensure robust regulation of these highly experimental treatments.

The principal steps that might be taken to help re-think the approach to trials in the regenerative medicine field are as follows.

• Because cell therapy trials are so varied there is no trial design that is suitable for all trials. Instead it would be useful to develop a ’basket of tools’ for cell therapy trials, allowing trialists to select the most appropriate design for their circumstances.
• Some of the options that should be considered include adaptive and factorial designs: this would allow for more flexibility during a trial as emerging data from the results suggested some modification to the trial parameters and what the researcher(s) come to see as more important factors that need to be considered, and how they might need to modify the choice of outcome measures and the specification of what is considered a ‘significant’ outcome as the trial continues. 
• In addition, information from other sources, especially non-trial based ‘clinical studies’, where patients are treated outside of a formal trials procedure, needs to be more effectively brought together and aligned with trials data.
• Finally, many clinicians will treat patients with cell therapies on a ‘one-off’ basis which is allowed under the so-called ‘hospital exemption’ provisions set by the regulators. Yet little of the clinical information from these interventions is actually systematically brought together. This could be done within the UK and more widely across Europe in order to provide further evidence of the value of diverse forms of cell therapy.