Last March, the Tufts Center for the Study of Drug Development revealed that the average cost to develop and secure marketing approval for a new drug now exceeds $2.5 billion. The largest proportion of that cost is attributed to clinical trials. In fact, despite long-standing industry-wide efforts to curb R&D expenditure, the cost of clinical studies continues to rise. It should come as no surprise. The increased complexity and size of trials, along with changes in protocol design to generate data for HTA submissions and the growing need for comparator testing to satisfy payer demands, has only added to spiralling out-of-pocket clinical costs. The trials and tribulations of reducing those costs are a familiar experience for drug companies that face relentless pressure to promote breakthrough technologies at an affordable price to global healthcare systems. To succeed, companies’ ongoing battle to demonstrate the value of their medicines must be aligned with a similar focus on driving value through their R&D operations. The question is: how?
A common approach is to outsource. As pharma strives for efficiencies in drug development, the deployment of Contract Research Organisations (CROs) to manage a full and diverse range of clinical trial services has grown significantly. According to Boston Consulting Group, 48% ($30 billion) of all clinical research investment in 2017 will be spent on outsourced services. By 2020, more than half (55%) of all clinical research investment will go to CROs. Projections from Research and Markets are even more bullish, forecasting that clinical trial outsourcing penetration will exceed 70% by the end of the decade. Whatever the growth curve, it’s clear that CROs are steadily establishing themselves as strategic partners to industry. In the process, leaders from within the sector are nurturing panoramic views of the clinical trials arena that could inform progress against pharma’s biggest strategic objectives. Here are six trends that are expected to shape the market in the next 12-18 months.
Trend #1: Reversing old trends
“As an industry we need to work hard to reverse trends that have been underway for decades,” says Patrick Jordan, enterprise head next generation clinical development, QuintilesIMS. “Our challenge is to address the right patient populations with protocols that are targeted, well thought through and tied to clinical endpoints. However, our efforts are undermined by familiar debilitating trends; half of investigators are unable to meet their enrolment goals; a third of investigators fail to enrol any patients at all. These staggering numbers have major implications; extended enrolment erodes commercial value and delays innovation from reaching patients. Similarly, whilst 60% of trials experience an amendment at some point, around a third of amendments are avoidable. That’s a $2 billion problem for the industry. We must reverse these trends.
“Thankfully, we’re seeing a greater push towards using data and analytics in a more intelligent way. As we understand more about biology and disease, we’re becoming more precise in targeting nuanced patient populations. Smarter analytics is allowing us to look at protocols as they’re being designed to identify gaps in patient populations or the areas where there are sufficient numbers of patients who aren’t exposed to medication. We’re also able to identify extraneous procedures that aren’t aligned to clinical endpoints and objectives. These enhanced capabilities are having a knock-on effect on patient recruitment and retention.
“But data alone isn’t the answer; it needs interpretation and application for it to become valuable. That’s the continuum; gathering data, analysing it and then establishing how we can apply it to solve a business issue. There’s a big opportunity to use insight to drive operational execution plans to reverse these long-standing trends.”
Trend #2: Deep science’s return
“Wholesale changes and pressures in the research and development environment are dictating a return to deep science and the collegial alignment of stakeholders, with significant ramifications for clinical research,” says Dr Michael Murphy, chief medical and scientific officer at Worldwide Clinical Trials. “Thirty years ago, R&D was like playing a game of chequers; it was slow, had predictable pathways, incremental innovations and the occasional big jump. In the 1990s the dynamics resembled poker – with big bold plays and blockbuster moves, and a focus on developing enabling technology and infrastructure. Today, research is a three-dimensional game of chess; it’s anticipatory and strategic and highly iterative. We’ve highly sophisticated technologies, nuanced patient phenotypes and a broader set of stakeholders that determine whether patients will have access to a product once it has been approved. The key requirement is to begin with the end in mind by building a value proposition into the clinical development programme.
“The modern trend is for the development of companion programmes that generate data that resonate with diverse stakeholders as well as supporting evidentiary standards for registration. The stakeholders that dictate physician adoption and subsequently patient access want to understand the impact of novel therapy on a system of care, reflected in outcomes measuring healthcare utilisation, and not exclusively in measures mandated for regulatory approval. This needs to be designed into the protocol, and accommodated by a strategic development programme. And it means that interventional and observational research teams need to partner to create a single effort that’s designed to demonstrate a “value proposition” to facilitate product access, once it has been approved.
“Clinical research is now a multi-dimensional problem; it’s chess not chequers. Our goal is to exploit permissive science to develop sophisticated technologies . But to get there, we need to create innovative and efficient trial designs to determine whether we have a ‘signal’ that’s worth pursuing. That necessitates an appreciation of the science supporting product rationale and the involvement of people that are in command of complex and nuanced trial methods.”
Trend #3: The CRO evolution“The relationship between sponsor companies and CROs has matured significantly,” says Dr Murphy. “Pharmaceutical companies, large and small, no longer limit CRO engagements to transactional services – they’re forming strategic partnerships that maximise CRO’s operational efficiencies and specialist capabilities, and leverage value-added services that align with CROs’ deep command of the science and clinical trial methodology. Sponsors are increasingly looking beyond the transactional delivery and inviting CROs to contribute to the conceptual evolution of programmes. Many CROs have expertise in translational medicine at both ends of the development spectrum; from animal to man and from development to commercialisation, and exploitation of that experience becomes a significant differentiation in the relationship.. The trend is towards establishing integrated project teams that work from IND-enabling studies right through to phase III and peri-approval activities. What’s more, in a permissive regulatory environment where accelerated approvals are increasing apparent, this integrated approach is helping to truncate development programmes and get treatments to patients quicker.”
Trend #4: Next generation tools“The next generation of clinical development is facilitating the emergence of data-centred tools to improve protocol design, enhance site identification and expedite patient recruitment,” says Patrick Jordan. “We’re now able to develop protocols that rigorously leverage data to ensure better patient outcomes. Similarly, we can apply deep, holistic insight to determine the most appropriate investigator sites, based on parameters such as historical performance, quality assessment and market intelligence. Finally, we’re able to use insight to compress recruitment timelines by identifying available patient populations around investigator sites that can unlock referral opportunities.
“The industry stands at the brink of harnessing insights and analytics to reverse decade-long trends in clinical research. These next generation tools will help make protocols stronger, identify investigators and patients with precision and – most important of all – accelerate access to medicines for patients with unmet needs.”
Therapeutic advancesAt the therapeutic level, the impact of transformative relationships and the smarter use of data in driving improvements in drug development is evidenced in some of the latest technologies reaching the market. These innovations themselves highlight two specific trends:
Trend #5: Immuno innovation“The advance of immuno-oncology therapies, along with the continued rise of Precision Medicines, has stimulated a level of excitement – and shifts in the landscape – that has not been experienced for years,” says Dr Andrew Zupnick, VP oncology strategy, Novella Clinical. “These immuno-oncology innovations, which re-engage the immune system to strengthen response against tumours, are transforming cancer care. They have the potential to work in combination with Precision Medicine – effectively turning on the immune system and providing a drug that blocks a specific mutation in a precise, targeted way. Moreover, the technology enables us to develop more effective drugs that attack a specific cancer rather than blasting the whole body. With data indicating that this class of drugs is more effective and less toxic than chemotherapy, it’s likely the development of immuno-oncology therapies will be a continuing trend for the industry. However, their development presents challenges in clinical research.
“The effects of the new class – checkpoint inhibitors – have been so significant that regulators have been keen to ensure these breakthrough therapies are accessible to patients as quickly as possible. This has led to some immunotherapies being approved in record times and standards of care shifting rapidly. As a result, it’s becoming harder for clinical research teams to design protocols for specific indications; with multiple checkpoint inhibitors competing for market share, which one do you choose when designing a forward-looking protocol? Similarly, protocols involving immunotherapy have increased in complexity in recent years. Despite the challenges, however, our current understanding of the technology and the science suggests there is a lot more to come from immuno-oncology and the next wave of treatments promises to be very exciting.”
Trend #6: Changing endpoints“Advances in immunotherapy and Precision Medicine are impacting the clinical endpoints that trials are set up to achieve,” says Dr Zupnick. “Traditionally, studies of oncology treatments have needed to be large and demonstrate an endpoint of overall survival to gain approval. Although survival is still the gold standard, the advent of immunotherapies and Precision Medicines has seen regulators become more amenable to utilising surrogate endpoints for approval – the most common being progression-free survival. In the past few years, the majority of FDA oncology approvals have been based on surrogate endpoints.
“The shift is another factor in the developing trend towards faster drug approvals. The implications for industry are significant; shortening the time-to-market, reducing development costs and realising the commercial value of innovation. These are major wins. Achieving them, however, requires a clinical research partner that knows the science.”
Trial by designThese trends underline the importance of protocol design and holistic trial management, from bench to bedside, in securing the commercial value of – and patient access to – life-enhancing medicines. These are exciting, if challenging times for clinical research. And CROs are right at the heart of it.
