With a strategic plan as the backdrop we can move on to the specifics of the science that must be applied to ensure the validity and optimisation of the protocol with respect to COAs.
This can involve one or more of the listed activities and is supported by PAREXEL subject matter experts.
Recommendations made as a result of the PAREXEL SME team consultation enable an informed discussion with the sponsor on instrument selection data collection modality and any additional preparation / costs required before a COA is ready for use in a study e.g. Qualitative or quantitative equivalence testing for instruments migrated to e-modality.
Evidence planning consists of a systematic approach to review the evidence for product value, assess all stakeholder needs and evaluate the evidence generation strategy.
We will now explore each of these elements in further detail
As we heard in Richard’s presentation, to succeed in today’s environment, companies must integrate payer input with regulatory, clinical and patient input throughout the product development.
With this in mind, it is essential to have a clear understanding of who will be the key stakeholders within your target therapy area in each of your targeted geographies. A stakeholder mapping exercise should be conducted to identify who are the key decision makers and who are the key influencers (for example from a regulatory, pricing, reimbursement, access and uptake perspective).
Not understanding the diverse needs of your key stakeholders can be costly. Failing to meet regulators and payer requirements can result in additional evidence requirements of failure to secure reimbursement.
In mid-2015 the hypercholesterolaemia drug Repatha® was approved by the European Medicines Agency (EMA) after it successfully lowered blood levels of LDL cholesterol (LDL-C) in randomized controlled trials.1 (LDL-C is a “surrogate marker” thought to predict clinical benefit.) However, EU payers did not consider the drug’s value was adequately demonstrated to grant reimbursement. In order to secure reimbursement, the developer had to wait for final data from larger trials that used more clinically meaningful, payer relevant cardiovascular outcomes including death, heart attacks, strokes and hospitalizations.2
The voice of the patient is likely to become even more important in light of regulatory developments
With the passing of the 21st Century Cures Act, the FDA is now required to issue new guidance on capturing and measuring patients’ experiences and perspectives; the final guidance is not scheduled until Quarter 4, 2021. In addition, the EU Clinical Trials Regulations coming into effect in 2018 will likely drive patient involvement in trial design. Trial protocols will be required to describe ‘where patients were involved in the design of the clinical trial, a description of their involvement’
Patients are also involved in HTA assessments, As part of dossier review process by IQWiG, input is sought from patients or patient organisations. As part of NICE’s evaluation by patients or their carers are asked for their views, with patient experts selected to take part in the appraisal.
Not understanding the diverse needs of your key stakeholders can be costly. Failing to meet regulators and payer requirements can result in additional evidence requirements of failure to secure reimbursement.
Once the stakeholders have been identified, their evidence requirements should be determined. A question to ask yourself, is how have you evaluated how your evidence will resonate with your key stakeholder groups. Will you conduct a literature review or will you utilize face to face engagement opportunities such as advisory boards, interviews/surveys with all stakeholders.
It is important to engage directly all stakeholders in evidence planning discussions – there is no replacement for hearing feedback directly and posing complex questions in person.
PAREXEL research indicates many companies have limited formal engagement from all commercial stakeholders
PAREXEL research suggests this is increasingly common practice but there are still opportunities for improvement. In a PAREXEL survey of 14 industry leaders, in commercialization, HEOR and/or market access, 75% of respondents stated that commercial endpoints were not well incorporated into trial design.
Involving all internal stakeholder groups early and throughout the planning process will enhance understanding and ability to address external stakeholder needs and commercial drivers!
A critical component for the successful commercialization of a product is its evidence generation plan. Drug development must integrate both clinical and market access perspectives from an early stage.
All internal teams should provide input into the codification and validation of the evidence generation plan at all phases – this is to ensure the perspectives and needs of all external stakeholders are considered.
The market access team should be involved to ensure the needs of payers are addressed and to ensure that market access endpoints are integrated into clinical studies.
PAREXEL conducted a landscape analysis to help a client decide between conducting a large, fast-enrolling trial of standard infections or simultaneously pursuing a smaller indication.
PAREXEL undertook a rapid assessment of the marketplace and the existing and future market for the primary indication was found to be overcrowded. Based on this analysis, PAREXEL recommended , pursuing the smaller indication as part of a fast-enrolling trial of standard infections.
Although pursuing the smaller indication would increase costs and increase the challenges of enrolment, PAREXEL advised that pursuing both indications would lessen risk to the company. Why? Because our landscape analysis clearly demonstrated that new treatments may not gain market share due to last-line positioning, whereas niche positioning could offer an advantage for pricing negotiations and ultimately uptake
Selecting the right patient population early on is critical. This is demonstrated by the case of pembrolizumab.
In the pivotal KEYNOTE-042 study, pembrolizumab and standard first-line platinum-based chemotherapy were assessed in treatment-naïve patients who had tumours with ≥ 1% PD-L1 positivity. The patients were stratified according to PD-L1 expression (strong (≥ 50%) vs. weak (1–49%)).
The extended use of pembrolizumab in the first-line setting is limited by the trial’s exclusion criteria with all the consequences for return on investment. The pool of eligible patients is likely to be closer to 10% rather than the 30% of all chemotherapy-naïve patients with NSCLC whose tumours express PD-L1 highly (≥ 50%).
The ADAPTABLE study, a three-year study of aspirin for the prevention of heart attacks and strokes in individuals with heart disease is using real world evidence. The cost of ADAPTABLE is estimated to be approximately $14 million. In comparison a classic RCT of similar size was recently completed at a cost of about $420 million.
Evidence planning consists of a systematic approach to review the evidence for product value, assess all stakeholder needs and evaluate the evidence generation strategy.
We will now explore each of these elements in further detail
Boost enrollment to onboard 3,000 patients in 2.5 years in highly competitive environment, and engage for >3-year follow-up
Clinical-value driven planning
Timely interim analyses
High-quality content relevant to the target audience