Can you tell us about your role as Senior Director & Global Head of Novel Trial Design at IQVIA?

 The Novel Trial Design initiative at IQVIA focuses on the application, where appropriate, of adaptive designs and master protocols.  In specific cases, especially early phase oncology research, these designs hold promise for improving efficiency and flexibility in evidence generation.  Leading this initiative is a tremendous opportunity to focus on innovation in design while also positively impacting the process of providing life-changing medications to patients.

In your opinion, what are the current challenges in drug development that benefit from innovation in design?

 Three well-known challenges can be addressed through the appropriate use of innovative designs such as adaptive designs and master protocols.  First, especially in early phase research, there are “known unknowns” regarding treatment effects, optimal dose selection, patient population selection, and even the best indication to target.  All of these questions require evidence to make good decisions and the use of innovative designs can, in many cases, streamline the collection of that evidence to speed time-to-market.  Second, different sub-populations of patients experience disease and treatment differently based on, for example, such factors as gender, ethnicity severity of disease.  The use of innovative designs can help assess and adjust evidence generation requirements to account for these differences.  Finally, innovative designs can incorporate the patient perspective by, for example, collecting evidence on multiple outcomes that really matter to patients to determine the best outcome measures for future data collection.

How can innovative trial designs for biopharma be leveraged to address these challenges and bring value to patients?

 Master protocol designs enable evidence generation on multiple indications for a given treatment (“basket trials”) and these are extremely useful in early phase oncology for “tumor agnostic” treatments that hold promise for multiple types of cancers.  Other variations on master protocols include testing multiple sub-populations/outcomes simultaneously and, in some cases, testing multiple treatments for the same indication.

 Adaptive trials allow, within pre-defined boundaries, adjustments to be made based on interim analyses.  This can include sample size recalculation (which can limit exposer to patients of unapproved treatments), and Bayesian designs which may reduce the size of a placebo arm (reducing the need to include patients who will not receive treatment).  Other uses of adaptive designs include optimal outcome measure selection and optimal dose selection.

What are some examples of successful innovative drug development strategies that you have been involved in?

Much of our work focuses on early phase oncology where the need to develop safe, effective treatments is so compelling.  While we cannot comment on specifics, we have been involved in the development of efficient designs for identifying the optimal dose for oncology treatments as opposed to the maximum tolerated dose.  This is very rewarding because it means patients will receive a smaller does without sacrificing efficacy.

How can stakeholders in the healthcare ecosystem, including regulators, payers, and patients, collaborate to support the adoption of innovative trial designs?

 We find that the best place for this collaboration is during clinical development planning, which is much earlier than typical trial design discussions.  Clinical development planning, among other things, attempts to identify the optimal set of trials to collect the necessary evidence to support the desired product profile of the treatment balancing time, cost and risk.  We find that when this planning takes into account the entirety of required evidence, not just that to support safety and efficacy claims, the use of innovative trial designs can play an appropriate role in streamlining the overall clinical trial strategy. 

 This is because by looking at not just clinical evidence requirements but also commercial evidence requirements (i.e., for payers, patients, caregivers and providers) it is likely possible to save time by combining what otherwise might be separate trials into a smaller set.  This reduces the overall time/cost/risk calculus (all other things being equal) and can get the right treatments to the right patients faster.

What are some of the ethical considerations that need to be taken into account when designing and conducting innovative clinical trials?

 Innovative clinical trials are certainly bound by the same ethical considerations as traditional trials. Typically the innovative designs focus on minimizing exposure to patients of experimental treatments and, where applicable, no treatment (i.e., a placebo arm).  This must be done while maintaining the integrity of the evidence generation process to ensure appropriate statistical power for the questions at hand.

 Because innovative designs may be more complex than traditional designs, it is especially important to ensure the added complexity does not compromise adherence with ethical considerations and requirements.

How do you see the field of clinical trial design evolving over the next 5-10 years?

 We see three main trends that hopefully will strengthen in the coming years.  First, the emphasis on trial design considerations much earlier during clinical development planning to optimize the time/cost/risk calculus in determining the best set of clinical trials to execute given the totality of evidence requirements (i.e., both clinical and commercial).  Second, the focus on the needs and desires of the patient to drive participation in clinical research in a “patient-centric” way.  And finally, the appropriate use of both experimental (i.e., through clinical trials) and real-world data to paint a more comprehensive picture of the safety, efficacy, and patient utility of treatments.

What advice would you give to young professionals interested in pursuing a career in drug development and clinical trial design?

 Innovation typically happens where disciplines overlap.  As such, identifying and specializing in more than one discipline positions you to be a driver of innovation, which has so many professional and personal rewards.  For example, in my case the intersection of economics and epidemiology created opportunities to apply both clinical and behavioural science to evidence generation in a different way. Also, focus on less tangible skills such as leadership and communication.

Finally, what excites you the most about the future of drug development and the potential for innovative trial designs to improve patient outcomes?

 We think just that—improving patient outcomes, especially the outcomes that matter to patients and caregivers.  Ultimately research is a means to an end, but the best research attempts to really understand that end from the patient perspective and then plan and execute in a way that optimizes time, cost and risk.  Innovative trial designs certainly play a role in that approach, but overcoming today’s challenges will require so much more.  There is a lot to be excited about!