Arabella Stanley: Historically, reimbursement was not a consideration during protocol design for clinical trials, but that must now change.
It’s worth noting that in 2017, of the 50 drugs submitted to HTAs, only 20 were reimbursed because of various evidence challenges. HTAs frequently question the relevance of endpoints, study populations, comparators, study geographies, and even the design of quality-of-life (QoL) questionnaires. They use the same process to review specialty drugs as non-specialty drugs, which doesn’t allow for any unique circumstances, such as, for example, when there might be data on only 20 patients in a rare disease study with no comparator. If they find any holes in the data, they tend to either restrict coverage to a subpopulation, or require more evidence – either from a retrospective real-world study or from a fresh trial. So, by not incorporating the needs of payers early into trial designs, you risk spending more money later on and delaying access to critical medicines for unmet medical needs.
Kelly Franchetti: The key is to adopt a true internal patient focus. The culture of clinical research is starting to shift from one directed by researchers to one driven by the needs of patients. Technology that constantly monitors and communicates with patients in real time makes it possible to assess the results of therapies at a granular level and over a range of real-world conditions. Involving patients and care partners in developing new therapies and trial designs and meaningfully engaging with them throughout the development and post-market process helps in generating irrefutable evidence of the value of therapies to patients in the real world.
Tanvi Ahuja: Early economic models (EEMs) should also be used to inform clinical development decisions, to develop evidence generation plans, and to support early pricing and market access discussions. It can answer questions such as “Is it worth the investment to collect better data?” “Where are the biggest gaps in existing evidence?” “What will be the economically justifiable price?” And even, “How will the choice of comparators, sub-groups, and efficacy inputs impact results?”
Franchetti: The patient voice needs to be incorporated into all phases of research and commercialisation, and the earlier the better. Trials in the oncology and immune disorder space are beginning to do this.
In rare diseases it is even more important to speak to the patients and care partners as often there are not many other options in clinical research to choose from, and it’s important we don’t assume their wants, needs and barriers. The rare disease populations are very unique and we need to fully understand the ecosystem/nuances surrounding them.
Consider the example in which a very sick child with a rare disease who is ventilator-dependent and wheelchair-bound has to travel back and forth to the trial site. It would be easy to assume that the parents would welcome a home nurse trial visit, but historically, many parents of children with rare and orphan diseases have given feedback opposed to a home visit because they view their home as the only space where their child feels safe from being poked and prodded and made to feel uncomfortable.
We rely on a variety of means – everything from one-on-one in-depth interviews, in person workshops to video journaling a ‘day in the life of a patient’ to gain a robust understanding of the patient perspective and perception. And, while there’s no substitute for direct patient input, it’s also equally important to also gather insights from caregivers, advocacy groups, and investigators.
As for digital technology to collect patient-reported data, it’s a phenomenal tool, but it also may not be right for every study or every patient. You really need to look at your patient population and consider factors such as patient age, health literacy, and socioeconomics. It is also imperative to consider what data is being collected and the rationale behind it. Patients want to understand why the monitoring is important and how it can drive their clinical outcomes and care.
Bill Row: Randomised clinical trials (RCTs) are limited in that they do not address real-life utilisation and real-world performance for new drugs. With the availability of RWE to do just that, stakeholders’ traditional requirements for evidence are evolving. RWE can estimate the effectiveness of a therapy in actual clinical practice, reflecting a larger population and longer-term outcomes.
Of course, lack of access to consistent real world data has historically been a problem. Accessing these data can be costly or time-consuming, which raises the question: how can we be more efficient and effective in obtaining and implementing RWE?
Devising a comprehensive RWE strategy can ensure that smart decisions are made in how to best choose, synthesise, and analyse available real world data (RWD) assets. By identifying what evidence will support regulators’ and payers’ decision-making, sponsors can develop an evidence generation plan across the product life cycle to leverage outputs and identify data gaps.
As clearer direction from stakeholders is released, confirmed and put into practice, there is major potential in the implementation of RWE generation strategies. While clinical trials will remain the most important source of knowledge for products in the early development stages, the impact of RWE and RWD on clinical trials and commercialisation will continue to grow.
Ahuja: At ICON, we have a process for working closely with our clinical trial teams at an early stage to make sure that the protocols meet the needs of HTAs and payers. One of the keys to success is early engagement. In one amazing case, we had patients, caregivers, payers and patient advocacy organisations all review the protocol beforehand — a process which will likely pre-empt many of the challenges that could otherwise occur later on.
Stanley: We believe that the best results come from an integrated approach that draws on expertise in real-world evidence strategy and analytics, patient insights and engagement, patient-reported outcomes, language services, strategic regulatory services, pharmacovigilance and risk management.
Bill Row is divisional principal, real world evidence strategy and analytics at ICON
Arabella Stanley is principal, global pricing and market access at ICON
Kelly Franchetti is vice president, global head patients insights and engagement at ICON
Tanvi Ahuja is senior analyst, global pricing and market access at ICON
ICON plc is a global provider of outsourced development and commercialisation services to pharmaceutical, biotechnology, medical device, government and public health organisations. ICON supports programs across all stages of drug and device development, from endpoint selection and PRO development, through clinical trials, to post-approval and scientific publication. ICON delivers integrated market access, pricing, communications and health economics solutions to demonstrate product value and support brand success around the globe. For more information visit, www.ICONplc.com/access