As competition continues to rise, and the healthcare landscape shifts, we feel a continuous need to find the next best thing. This has led us to invest in innovation, especially within R&D. But do we really understand the impact of what we are trying to achieve?

“Innovation” is a term that gets thrown around a lot in the pharma industry, but we often do not understand its full context. Innovation is not limited to technological and digital solutions per se, but also encompasses the way you design a clinical trial, set outcomes and collect data, for example. Taking this a step further, it may also involve how pharma tries to play to the strengths of trial outcomes to convince regulators and payers of the therapeutic value of its asset.

And this all makes sense – pharma players feel the pressure of high R&D costs, of policy makers and payers increasingly scrutinising the value of drugs, and of the increasing burden of disease mandating pharma to deliver the best solutions for patients in the quickest time possible. Take 2020’s events, for example.

This however begs the question whether many pharma companies are setting themselves for a tortoise and hare situation, where the rush for ultra-quick results does not ultimately deliver a grand “win”. When the race is on and time and tools are of the essence, how much innovation in R&D is too much?

 

Complex drivers are leading the industry to “revamp” clinical trial models, increasing speed-to-market and efficiencies in data collection

Measurable drug efficacy aside, access to a therapy is hardly undeniable particularly when demonstrated through a perfectly randomised controlled trial. Where this is not feasible, and differences between disease types, availability of patients and novel drug targeting (e.g. gene-fusion targeting in tumour-agnostic therapies) are accounted for, pharma has ushered to adopt smart trial designs.

From single-arm (SAT) and basket, to umbrella and super umbrella trials, pharma companies often invest in these models driven by time and cost savings, ethical reasons – recent CAR T trials – or to maximise on data collection. Therefore it is not surprising to see a steep rise in single-arm trial regulatory submissions from 2011 to 2019 predominantly in niche oncology and metabolic diseases (IQVIA Global Data).

And smart trial design can be great in propelling clinical development, and helping therapies reach patients faster. As my colleague Laura Haden-Smith discusses, COVID-19 reinstated the role of partnerships and innovation for pharma, where we witnessed a surge in a global network of adaptive clinical trials testing multiple interventions simultaneously! Of note are the set of Adaptive COVID-19 Treatment Trials (ACTT) from NIH and RECOVERY from the University of Oxford that paved the way to collecting multiple outcomes and validating some of the treatments that were broadly used (e.g. remdesivir) in an effort to combat the pandemic.

Speed is good, but is the quality and validity of data that we often collect as high as we need it to be and what does this mean for patients?

 

Trial designs focused on rapid approval create incomplete datasets, which can ultimately dampen access outcomes and affect patient access to care

Of course, the development of therapeutics to combat COVID-19 is a prime case study in accelerated R&D on a global stage. However, it does not exactly follow the typical model. Everything has had to speed up to deliver therapeutics because the stakes were astronomical. Even if pharma ends up playing catch-up on data, it’s a risk-reward situation – and a life one at that. But outside of the spotlights of the pandemic, stakeholders often make very different judgement calls.

It would be naïve to think that new solutions do not come at a price. How do you know when you are compromising on elements that are crucial to success? Unconventional clinical trials often result in less comprehensive, incomplete data sets accompanied by surrogate endpoints. Despite regulators such as the FDA supporting the use of non-conventional endpoints, external analyses question their validity and challenge them accordingly. And when reaching discussions with regulators and payers, everyone and ultimately patients, pay the price.

An internal benchmarking assessment of drugs that sought approval via SATs by Eradigm revealed longer periods of negotiation than standard HTA assessments with complete comparator groups, less favourable pricing outcomes for pharma, lengthy post-authorisation data collection commitments and positioning in later lines of treatment.

When not carried out for the right reasons, are non-comparative and innovative clinical trials eventually worth it?

 

Adopting a patient-centric approach to trial innovation facilitates meaningful results and optimal care at its core

Innovation in R&D and trials is not necessarily a trend anyone should try to fight. But when considering deploying innovative trial designs and tools, how can we strike a balance and get it right

Arguably, a significant solution is to adopt a patient-centric approach in the early design stages, to yield meaningful outcomes, shaped by patients to benefit patients. For pharma, the trend has already picked up even in clinical trial design with companies such as Bioverativ tapping into their social network with MyHealthTeams to seek patient input on trial design and endpoint selection. The overall result? Meaningful data, reduced administrative burden and protocol amendments, and an increase in trial enrolment and retention.

But it does not stop there. Making trial completion and endpoint selection a success requires the alignment of all stakeholders to understand what it is that patients need and help each other achieve it. Regulators and HTA bodies, such as NICE, have made moves by tailoring their guidelines and offering early consultation to pharma to inform of their expectations and contribute to study success. This might be a time, where the industry is called to work together and prioritise the apple of their eye: people.

Responsible clinical innovation requires us to continuously question what matters

Let us remain ambitious, as there are many tools and solutions out there that we can consider to get this right. In a post-pandemic era, where COVID has catalysed the adoption of remote models and digital tools for example, we need to first understand, and then consider how to leverage virtual clinical trials, digital and remote patient monitoring, and decentralised trial models to drive “smart, measurable change” and deliver value.

To do that, we need to continually measure the impact of innovative initiatives. And before we commit to a course of action, we ought to ask what is achievable, what are the risks and how do we find the best solution for long-term business strategies, for the healthcare landscape and importantly, for patients around the world.