Pharmaceutical companies invest huge amounts of money and time into the development of new medicines, yet it is the nature of the very difficult research and development (R&D) process that few candidate medicines that enter clinical studies are ultimately approved.
For those that do reach the market, the R&D process can have taken 12 years or more. Therefore, improving the success rate and accelerating clinical development are top priorities for both pharmaceutical companies and the medicine regulatory authorities, so that new medicines can be made available to patients faster.
This stimulated the ABPI to hold a horizon scanning meeting with the Medicines and Healthcare products Regulatory Agency (MHRA), as well as other global regulators, under the auspices of the Ministerial Industry Strategy Group (MISG) New Technologies Forum series to advance thinking around innovation in clinical trial design. An outcome of the meeting was the initiation of a cross-industry collaboration led by the ABPI Experimental Medicine Expert Network, with statisticians in the pharmaceutical industry (PSI), to share experiences, learnings, and best practice in modelling and simulation of clinical trials.
Clinical trial simulations are an integral part of clinical development programmes and can be used to improve understanding and decision making at every stage of medicine development. Our collaboration with the PSI has produced a report, Clinical trial simulations – an essential tool in medicine development. In its simplest form, a clinical trial simulation is the study of the effects of a medicine in virtual patient populations. Mathematical models, which incorporate information on physiological systems, are used to help understand the likely impact of factors that might occur in the actual clinical trial, such as types of patient biology, treatment effects, and even how medicines are taken.
Simulations can be performed with differing scenarios, to quantify key issues related to medicine safety and efficacy, and to define the optimal study design of the clinical trial and the target patient population. Hence, simulations should allow us to predict results in actual clinical trials with greater certainty, perhaps reducing the number of patients studied. In addition, simulations help sponsors make better informed decisions on when to halt development of a new candidate medicine, which reduces unnecessary patient exposure as well as lowering overall development costs.
Clinical Proof of Concept (PoC) is a key decision making point in the earlier stages of clinical development. Initial proof that the medicine may be effective in a clinical setting is a key trigger point for further major investment by sponsors of the more complex studies of late clinical development. To be of value, PoC therefore requires a definitive outcome. Simulations can help achieve definitive outcomes by feeding information into PoC design, to answer three critical questions: how much medicine needs to be delivered to the target and for how long? Is the medicine achieving the desired pharmacological activity (i.e. proof of mechanism)? Which patients will respond to treatment?
Clinical trial simulation will play an increasingly important role in development programmes and for regulatory approval. Use of this tool to test assumptions of the biological and therapeutic effects of a new medicine at an earlier stage of development should lead to clinical trials that have a greater probability of success. We recommend that with time, this is further characterised to improve their use and the efficiency of medicine development.
Dr Louise Leong
Director of R&D Policy