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 healthcare decision-making process.
There are a range of perspectives on 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 and processes of regulatory and health technology assessment (HTA) agencies as well as pharmaceutical R&D, which are the main focus of this RWE Navigator. Other perspectives include those of health care payers (insurers) and 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 as well as the balance of efficacy (benefit) and risk.
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 the clinical plan and the plan for achieving regulatory approval (marketing authorisation), as well as on scientific, manufacturing, marketing and other commercial considerations. They also consider the evidence needs of health technology assessors and payers, and put in place plans for evidence generation.
Throughout the development programme the team works collaboratively with clinicians to understand the potential value of a new medicine and how it is likely to be used. 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 team. 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 regulatory submission.
Health technology assessment (HTA)
Reimbursement agencies are responsible for assessing the benefits and costs of introducing new medicines to local healthcare systems. There are multiple agencies across Europe and they vary in their functions and responsibilities. Most include some form of health technology assessment (HTA) as a key component of their review of evidence.
Typically HTAs will consider both clinical and cost effectiveness. In this context, clinical effectiveness is a comparison of the health outcomes of the 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 cost to the healthcare system.
Patients and carers
Patients (and carers) will benefit from new medicines that fulfil an unmet medical need or improve current care. However, they are not just potential users at the end of the development, and 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 patient 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.