GetReal aims to show how new, robust methods of real-world evidence (RWE) collection and synthesis could be adopted earlier in pharmaceutical research and development (R&D) and the decision-making process for new medicines.
There are a range of perspectives which influence the definition, valuation and measurement of relative effectiveness. Ultimately, the perspectives of greatest importance are those of the patient (and carer) and clinician. These will be reflected in the decision-making perspectives of regulatory and health technology assessment (HTA) agencies as well as manufacturers (pharmaceutical R&D), which are the main focus of this RWE Navigator. Other perspectives include those of health care payers (insurers), health care providers, employers and health policy makers.
- Pharmaceutical research and development (R&D)
- Health technology assessment (HTA)
- Patients and carers
- Other perspectives
The responsibility of regulatory agencies is to provide authorisation for manufacturers to be able to sell specific medicines in the relevant countries. In Europe, the European Medicines Authority (EMA) co-ordinates authorisations across member states, based on recommendations of selected ‘rapporteur’ states and mutual recognition procedures.
Regulatory agencies engage regularly with manufacturers to assess their clinical development plans and to approve constituent studies. They are also responsible for assessing manufacturing quality.
In the development phase, regulatory agencies have traditionally needed high-quality ‘explanatory’ trials to give unbiased estimates of efficacy and safety. However, they have become increasingly interested in the need to collect data on safety and efficacy post-authorisation and the balance of efficacy (benefit) and risk (harm).
There are opportunities for manufacturers to engage formally with regulatory agencies throughout medicine development, and to participate in collaborative scientific advice sessions with HTA agencies.
Pharmaceutical research & development (R&D)
Multidisciplinary medicine development teams are typically formed during phase 2 of development (5-7 years before launch of the medicine). Their focus is on developing and executing the plan for clinical studies directed at achieving regulatory approval (marketing authorisation), as well as on scientific, manufacturing, marketing and other commercial considerations. More recently there has been increased focus on the evidence needs of health technology assessors and payers, for which plans for evidence generation are also put in place.
Throughout the development programme the medicine development teams work collaboratively with clinicians to understand the potential value of a new medicine and how it is likely to be used in routine clinical practice. Many clinicians will also serve as investigators in clinical trials.
Decisions to progress to the next phase of development, or to launch the medicine, are usually made by senior management, following the recommendations of the medicine development teams. Towards launch, the focus shifts towards commercial teams who liaise closely with sales and marketing teams in each country, and medical affairs professionals who oversee clinical and scientific activities during and after submission to regulators for marketing authorisation.
Health technology assessment (HTA)
Reimbursement agencies are responsible for assessing the benefits and costs of introducing new medicines to local healthcare systems. There are a variety of agencies across Europe, operating at national or regional levels, who vary in their functions and scope of responsibility. Most agencies include some form of health technology assessment (HTA) as a key component of their review of evidence.
Assessments performed by HTA agencies will generally consider clinical effectiveness and in many cases cost effectiveness will also be considered. In this context, clinical effectiveness assessment is a comparison of patient and clinician-relevant health outcomes of a new medicine with those of available treatment alternatives (the comparative effectiveness). Cost-effectiveness assessments typically focus on whether the additional health benefits associated with the new medicine are justifiable given the potential additional costs to the healthcare system.
Patients and carers
Patients and carers will benefit from new medicines that fulfil an unmet medical need or improve the delivery of care. However, they are not just potential users at the end of the development: their involvement throughout the development process is key to ensure that their needs are adequately considered and reflected in the final decision-making.
The unique perspectives of patients and carers can result in diverse attitudes and preferences towards the different outcomes that constitute clinical effectiveness (‘what is important?’). Patients might also suggest different criteria to assess the acceptability of the various treatment options.
Communication with patients, carers and patients’ organisations is important throughout medicine development. Most regulatory and reimbursement agencies formally seek the views of patients and carers through committee representation and public consultation. Capturing the diversity of opinion enables decision makers to be sensitive to the needs and views of patients.
Clinicians’ perspectives are important to explain what outcomes are important for them when deciding which treatments to offer patients and monitoring the impact of therapy. They can also provide insights into the patient perspective. Many may be involved in decision-making about which services and treatments to offer at a local healthcare payer or provider level.
The views of clinical professionals are sought extensively by product development teams in pharmaceutical R&D, as well as regulatory authorities and reimbursement agencies, where they have prominent roles as committee members or expert consultants.
Other perspectives that may be important for new medicines include those of national and local policy makers, local healthcare insurers or commissioners (frequently referred to as ‘payers’), healthcare provider organisations and employers (who pay for health insurance, especially in US).
Although they all have requirements for evidence of (relative) effectiveness, these have not been the specific focus of the GetReal programme.