Medicines Adaptive Pathways to Patients (MAPPs) seek to foster access to beneficial treatments for the right patient groups with high unmet medical need at the earliest appropriate time in the product life-span in a sustainable fashion.

After a long and complex development process and once a new medicine is approved by the European Medicines Agency (EMA), in most member states an assessment will take place to determine whether a medicine will be be reimbursed in its healthcare system.  This process can take 10-12 years in average. MAPPs can offer opportunities to optimise (and potentially shorten) many steps in the medicines life-cycle.

Adaptive pathways can be defined as a prospectively planned, iterative approach to bringing medicines to market. The iterative development plan will initially target a well-defined group of patients that is likely to benefit most from the treatment. This is followed by iterative phases of evidence gathering and progressive licensing adaptations, concerning both the authorised indication and the potential further therapeutic uses of the medicine, to expand its use to a wider patient population as more data become available.

A key aspect of adaptive pathways is the involvement of all relevant decision-makers in the process across the life span of the medicine, including those who decide about patient access in the EU Member States, to help determine which medicines could be appropriate for adaptive (iterative) development. Stakeholders will jointly agree to a data generation plan to meet the needs of regulators, health technology assessment bodies (HTAs), payers, patients and health care providers. It will also to ensure that the use of the medicine is well monitored and managed (see http://adaptsmart.eu/early-access-is-it-worth-it/)

MAPPs, is a multi-stakeholder approach to developing and evaluating new medicines. In order for outcomes-based healthcare to succeed, we need to know the performance of a treatment, both at a population level and an individual level. We need to expand our toolbox, and RCT data needs to be complemented with more information, notably more real world information.

In order to harness these large volumes of real world data, we also need rapid-cycle analysis providing the ability to process this data, almost in real time, in order to update decisions and minimize realised harm. This information can be used by regulatory decision-makers to adapt a products’  information, or reimbursement decisions.

Many initiatives are working towards achieving these points which bring us closer to realising this goal. These include the European Medicines Agency’s adaptive pathways pilot, completed in August of 2016, as well as the Innovative Medicines Initiative projects such as ADAPT SMART. The hurdles standing in the way of successfully implementing outcomes-based medicine are both technical and political, and collaborative initiatives like ADAPT SMART work to address both types of challenges.

A medicine going through MAPPs will have demonstrated a level of efficacy and safety that warrants and justifies the use of an adaptive pathway. Any medicine approved for MAPPs will be accompanied by a real world evidence package that will monitor the actual performance of the new medicine over the entire lifecycle of its use in patients. This represents an increase in the level of evidence over current regulatory pathways. MAPPS will provide continuous risk/benefit information for better follow-on coverage decisions at the member state level, and a more accurate safety profile to regulators, payers, and patients.

The purpose of ADAPT SMART is to lay the groundwork for the implementation for new methods for the development and evaluation of new medicines:

• Facilitate Real World Evidence generation and remote monitoring to effectively evaluate the actual performance of a new medicine;
• Help develop or implement tools and processes to allow for the continuous reevaluation of a medicine’s performance, ideally in real time and in the real world, which includes adaptive reimbursement systems;
• Help implement procedures in collaboration with patients, national health care systems to ensure that the benefit/risk of new medicines is fully understood by all participants of MAPPs;

A transformative medicine is one that does more than simply addresses a high unmet medical need, as it must also lead to a substantial medical benefit greater than existing therapies, if any exist. MAPPs will focus on medicines that can make a transformative impact on patients lives, and have a high probability of a gain in quality of life while balancing benefit and risk.  See discussion paper on Engagement criteria for MAPPs

Recent research published in the Journal of the American Medical Association (JAMA) investigated the effectiveness of oncology products released on the basis of a surrogate endpoint – a very challenging way to prove a medicine actually works. The JAMA study showed that roughly 20% of these new medicines provide a “proven overall survival benefit.”

The ADAPT SMART consortium is looking into how modern methods for e.g. investigating effectivess (as in the example above), indentifying responders faster or analysing the performance of new medicines in “real world” more effectively, would contribute to bringing needed medicines to patients earlier using the MAPPs framework in partnership with patients, payers, regulators, industry and health care providers.

A key component of MAPPs is bringing various stakeholders from many member states around the table earlier in the medicines development process to determine what information is needed to make better decisions sooner. This might help making the different assessments in member states more efficient for these medicines targeting areas of high unmet medical need. However, under the current system individual member states will make their own decisions about reimbursement of medicines, and this will not change under MAPPs.

The application of MAPPs will allow for pharmacovigilance to occur simultaneously with evidence generation for effectiveness, with the use of real world evidence at the launch of the MAPPs process.

ADAPT SMART will develop as part of its programme, as well as in partnership with other IMI projects such as Big Data for Better Outcomes or GetReal, MAPPs tools and methodologies to make the MAPPs concept a reality over the entire lifetime a medicine is perscribed, in partnership and collaboration with payers, patients, practitioners, and industry.
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Patients are at the center of the MAPPs process, as there is not a decision in MAPPs that can be answered suitably without patient engagement.

• Patient organisations are part of the ADAPT SMART Consortium. The European Patients’ Forum and EURORDIS-Rare Diseases Europe provide their experience, lead several of the ADAPT SMART tasks and facilitate broader patient community input into the project.
• Beyond the project, it is now widely accepted that meaningful patient engagement in the medicines value chain adds to the quality of the decision making processes and of medical innovation in general. This is not different with MAPPs, and patients will have an important role to play at every stage of the process (see Seamless Pathway and Decision Making). Their feedback, and active participation alongside other key stakeholders, will determine ultimately if a medicine is successful through MAPPs.