Table 3 Characterisation of potential benefits to patients, clinical trials and funders

Ethics: patient benefit

Early stopping of trials as soon as there is sufficient evidence to answer the research question(s) means:

‘It really depends on the type of AD so if you have a GSD (Group Sequential Design) then of course you can stop early for futility or overwhelming effect and this clearly has many ethical and financial advantages. So for futility stopping –if it doesn’t work you can stop early on and the patients don’t get exposed to a drug that does not work or if you have overwhelming effect that is also very positive you can move on with the development of your drug and you don’t have to finish the whole trial’. (QL11 Statistician)

▪ Minimisation of unnecessary over recruitment of research patients

▪ Acceleration of the evaluation of interventions, approval and commissioning into practice. Thus, patients receive effective interventions quicker

‘…from a patient point of view the sooner that if there is a new intervention that is really effective then we want to get that into NHS (National Health Service) practice, equally if it is dangerous or if there is anything that we shouldn’t be using then we would want to get that out and into guidelines and NHS practice as much as possible’. (QL01 CTU Deputy Director, Proposal Developer)

▪ Minimisation of the exposure of patients to potentially ineffective and/or unsafe interventions

▪ Patients are likely to be allocated to interventions to which they have a higher chance to respond better; vital in critically ill patients

‘When you certainly have a limited patient pool like orphan disease implications where you know you’re not going to be able to actually recruit sufficient patients for a full Phase 2/3 traditional development programme and we accept and understand that, as regulators and industry, you’re offered appropriate incentives under orphan designation in the EU (European Union) and US (United States). So, there’s undoubtedly a challenge - an opportunity to maximise the best use of patients. I've once actually seen a combined Phase 1/2/3 study, all in one go’. (QL16 Regulator)

▪ Identification of group of patients who are most likely to respond to the intervention [61, 62]

Efficiency in trial design

▪ Mitigating the risk of making wrong design assumptions

‘One of the things that I always tend to tell people is that ADs will make you address the objectives of interest enabling you to make the right decisions earlier rather than later, for example, the biggest opportunity is stopping poor drugs early, most of our drugs fail, 90 % of the drugs that we start developing in phase 1 never get to the full registration, we should be killing those drugs as early as possible and ADs allow you to do that, whether it is in phase 2 or 3 there is always that opportunity to stop early for futility’. (QL15 Statistician)

▪ Allows simultaneous testing of multiple interventions from a competing list with option for dropping inferior interventions in a single trial rather than multiple series of two-arm trials [46]

▪ Allows the answering of research questions quicker to expedite decision making

‘The main advantages of ADs accrue to funders because funders are not paying for essentially redundant data and ethically I think there is a benefit to patients because clearly we don’t want to be recruiting patients to trials when there is no significant potential of that trial and additional data giving you any new information’. (QL04 Chief Investigator, Vice Chair - Public Funder)

▪ Efficient use of a limited patient pool, particularly in rare or orphan disease implications

▪ Efficient use of a finite pool of clinical chief investigators

Value for money for funders/sponsors

▪ Avoiding pursuing the lost cause when trials are stopped early for futility

▪ Efficient use of available research resources. Stopping trials early means resources are reallocated to other promising or priority areas