Summary
Sometimes more than one treatment option is available to patients. A series of factors goes into deciding the best treatment path for an individual – for example: efficacy and availability of treatment, access to treatment, risk and severity of side effects, convenience, age, expense, how invasive the treatment is, what the follow-up is like.
New therapies should not only target clinically relevant outcomes but also what the patient feels is important. For instance, patient preference researchers learned from patients with chronic obstructive pulmonary disease (COPD) that it is not only clinically relevant outcomes – like lung function and hospitalisations – that are important. Patients also want treatments that decrease excessive coughing and mucus secretion, which disturb their usual daily activities.
Where there are a variety of treatment options available, trade-offs come into play. For instance, for some patients with rheumatoid arthritis, physiotherapy and exercises might be the preferred route, whereas others will opt for a pill, while still others could benefit more from injections into the affected joints. For each of these options there are trade-offs – pills are easy to take but come with side effects; injections are fast-acting and potent, but are also invasive, and the patient has to travel to the medical centre regularly for treatments which may be inconvenient.
Knowing what preferences patients have can aid drug development. There is little point in a pharmaceutical company spending time, money, and resources on developing a treatment if patients struggle with it because it does not address their needs sufficiently. Integrating patient preference studies into the existing development programmes can help researchers to understand what is most important for patients and the acceptable trade-offs.
Before 2016, although it was clear that patient perspectives (including carers, parents, or patient organisations) should be considered when developing medicines, when and how to do that was uncertain. Regulators like the European Medicines Agency (EMA) were seeking an evidence-based framework, so the PREFER project set out to assess when and how patient preferences on benefits and risks should be incorporated into decisions on medicinal products.
Building an evidence base
The first steps towards an evidence-based set of recommendations were to carry out literature reviews and conduct a series of interviews with stakeholders. 143 stakeholder interviews were conducted (where stakeholders included patients, industry, regulators, and HTA bodies or reimbursement agencies), six literature reviews were compiled and eight focus group discussions held.
Three main disease areas – lung cancer, rheumatoid arthritis and neuromuscular disorders were the initial focus for patient preference case studies in the PREFER project. However, the project finally compiled a series of ten case studies covering not just these disease areas but also others, such as diabetes, chronic obstructive pulmonary disease (COPD) and haemophilia. The complete set of case studies can be found on PREFER’s website.
The project needed to assess the variety of methods for conducting patient preference studies that the literature reviews had outlined. Ten qualitative methods and 23 quantitative methods were identified to explore and elicit patient preferences. Some of the methods were then evaluated in case studies.
How and when to use the PREFER recommendations
The recommendations developed by PREFER and the Qualification Opinion from EMA are the ultimate outputs of the project. Based on stakeholder needs, preference study methods and case studies, these recommendations serve not only to aid decision-makers to decide when and how to elicit and integrate patient preferences into medicine development, but also to outline under which circumstances patient preference studies are necessary, and what type of methods to select.
There are circumstances where a patient preference study is not necessary, and these are also laid out in the recommendations. For instance, new patient preference studies are not likely to add value if one treatment option is clearly preferable to another; if there are no side effects or disadvantages with a new treatment; or where patient preference is clear from previous high-quality and up-to-date research. In circumstances where the patient has no choice – for example, a surgeon selecting which tool to use – it is also not helpful to run a patient preference study.
PREFER identified 15 critical points in the medical product life-cycle where patient preference studies should be considered.
Gaining regulatory approval
While the PREFER Recommendations were under development, PREFER asked the European Medicines Agency (EMA) for a qualification opinion of the framework and a ‘points to consider’ document on method selection. In April 2022, the EMA committee responsible for human medicines, the Committee for Medicinal Products for Human Use (CHMP), issued a positive public qualification opinion endorsing the PREFER approach from the regulatory perspective.
From the perspective of the public-private PREFER consortium, the endorsement of the PREFER framework by the EMA gives preference study leaders confidence to use the PREFER recommendations and published results as guidelines for patient preference studies. It also provides a solid basis for future interactions between patient preference study sponsors and regulators.
PREFER’s impact and the future of patient preference studies
By the time PREFER came to a close in May 2022, the recommendations had been downloaded 3 000 times from the website, and a set of eleven templates for patient preference studies had been set up by the project. 43 peer-review publications have been published by the project, and several webinars were broadcast which are publicly accessible.
The PREFER Expert Network was set up to continue the work of PREFER past the project’s end. Composed of 20 academic and industry researchers from PREFER as well as two new members, the European Patients Forum (EPF) and the USC Schaeffer Center for Health Policy and Economics, the goal of the network is to foster the application of PREFER’s recommendations in a systematic and sustainable way by industry, academia, regulatory and HTA agencies.
Achievements & News
June 2022
Taking patient preferences into consideration when developing a therapy would seem common sense. Yet it is only relatively recently that...
A major regulatory milestone has been reached for researchers working on the IMI-funded project PREFER, who have been investigating and testing the best ways to include patients’ voice in medicine development and decision-making.### A positive draft opinion from the European Medicines Agency (EMA) on the consortium’s proposed framework for patient preference studies, as well as a document outlining points to consider when selecting methods for structured patient input to medical product decision-making, recently went through a public consultation.
The IMI-funded PREFER project is currently finalising a set of recommendations that industry, regulatory authorities and HTA bodies will be able to use to develop guidelines on how and when to include patient perspectives on the benefits and risks of medicines.
In parallel, the consortium worked out a research framework for patient preference studies, as well as a document with points to consider when selecting the methods for carrying out a patient preference study.
The project submitted an application for a qualification opinion to the EMA-EUNETHA (the first joint regulator an health technology assessment bodies joint procedure), and the EMA released a draft opinion that endorses both the framework and the points to consider document, ‘as a comprehensive reference document for planning and conducting patient preference studies’.
The draft opinion underwent a one-month consultation period so that researchers, patients, pharma companies, regulators, HTA bodies or anyone else could contribute their comments before EMA releases its final opinion.
Find out more
- Read the article in full
For innovative treatments and treatments for rare diseases, finding a way to include the patient perspective in decision-making can be crucial. With answers from 117 people with haemophilia, PREFER researchers present their results from their clinical case study about haemophilia patients’ preferences for gene therapy.### They found that patient preferences vary greatly. And that informing patients about gene therapy can facilitate acceptance.
The results from this clinical case study showed the importance of patient education on gene therapy, as the researchers included an educational tool on gene therapy at the start of their survey and the time that patients spent on this tool was found to have an impact on the results. The patients who took more time to take in the educational materials offered, tended to be more accepting of gene therapies. For innovative treatments, educational tools may be especially useful to collect the informed views of patients. This to make sure they have the information they need to make informed trade-offs between the different benefits and risks of current treatment options and gene therapy.
Find out more
- Read the article in full
There is now broad recognition that patients can and should be involved in all stages of medical research and drug development, as understanding patients’ preferences can improve decision-making. However, putting ‘patient-centricity’ into practice is not always easy. IMI’s PREFER project has now identified 15 critical decision points in industry, regulatory and health technology assessment (HTA) decision-making where input on patient preferences can support the process.###
Their findings are published in the journal Health Policy. ‘Currently, PP [patient preference] information is not considered as obligatory information to submit for any of the MPLC [medical product lifecycle] decision-points,’ the scientists write. ‘However, PP information is considered an important component by most stakeholders to inform future decision-making across the MPLC. The integration of PP information into 15 identified decision-points needs continued discussion and collaboration between stakeholders.’
First author Chiara Whichello of Erasmus University Rotterdam says: ‘We do see regulators and HTA having to take more steps to integrate patient preference information into their decision-making processes, compared to industry. Simply because they have to also take into account how much weight should be given to patients’ preferences compared to other required information, such as safety and cost-effectiveness.’
Find out more
- Read PREFER’s news item
- Read the paper in Health Policy
Three IMI projects – c4c, EUPATI and PREFER – are cited in a new Orphan Drug Development Guidebook released by the International Rare Diseases Research Consortium (IRDiRC). ###Developing ‘orphan drugs’ (i.e. drugs for rare diseases) is highly challenging, and just 5 % of rare diseases have an approved treatment. The IRDiRC describes the new guidebook as ‘a patient focused guidebook that describes the available tools, incentives, resources and practices for developing traditional and innovative drugs/therapies for rare diseases and how to best use them.’ It lists a range of resources from organisations around the world, including IMI.
c4c aims to generate a sustainable infrastructure that optimises the delivery of clinical trials in children, and the guidebook suggests this could be useful for those developing medicines for rare paediatric diseases.
On EUPATI, the guidebook describes its patient education resources as ‘very relevant to rare disease medicines development and highly useful and appreciated by the rare disease patients that finished the academy and use the toolbox’.
On PREFER, the guide highlights how patient preference studies can be useful during regulatory benefit-risk assessment for certain drugs in several major ways.
The guidebook is presented in an article in Nature Reviews Drug Discovery. ‘By enhancing the use of available tools, delays in development timelines can be avoided, risks and costs reduced, and patient and regulatory acceptability improved,’ the authors conclude.
Find out more
- Read the paper in Nature Reviews Drug Discovery
- Read the guidebook entries on c4c, EUPATI, and PREFER
- Orphan Drug Development Guidebook Materials on the IRDiRC website
Two IMI projects focusing on patient engagement, PARADIGM and PREFER, have signed a memorandum of understanding (MoU) to enhance collaboration between the projects and to maximise results. The MoU outlines how the projects will work together and share ideas. ###While PARADIGM is broadly focused on patient engagement at three points in the research and development process, PREFER looks at how and when it is best to perform and include patient preferences in decision making during the medical product life cycle. Through the MoU, the two projects hope to identify areas of mutual interest; identify any gaps that are hindering progress; establish collaborative activities to address these gaps; and share knowledge and data. The projects will also mutually participate in project events and use each other’s communications channels to promote news and results. In a joint statement, the projects write: ‘There is an ample opportunity to leverage the work of these projects, to avoid duplicate efforts as well as maximise results.’
Participants
Show participants on mapEFPIA companies
- AbbVie Ltd, Maidenhead, United Kingdom
- Actelion Pharmaceuticals LTD, Allschwil, Switzerland
- Amgen Limited, Cambridge, United Kingdom
- Astellas Pharma Europe BV, Leiden, Netherlands
- Astrazeneca AB, Södertälje, Sweden
- Bayer Aktiengesellschaft, Leverkusen, Germany
- Csl Behring GMBH, Marburg, Germany
- Eli Lilly And Company LTD, Basingstoke, United Kingdom
- F. Hoffmann-La Roche AG, Basel, Switzerland
- Janssen Pharmaceutica Nv, Beerse, Belgium
- Merck Kommanditgesellschaft Auf Aktien, Darmstadt, Germany
- Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, United States
- Novartis Pharma AG, Basel, Switzerland
- Pfizer Limited, Sandwich, Kent , United Kingdom
- Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
- Takeda Pharmaceuticals International AG, Glattpark-Opfikon (Zurich), Switzerland
Universities, research organisations, public bodies, non-profit groups
- Centre Federal D'Expertise Des Soins De Sante, Brussels, Belgium
- Erasmus Universiteit Rotterdam, Rotterdam, Netherlands
- Forum Des Patients Europeens, 1040, Belgium
- Katholieke Universiteit Leuven, Leuven, Belgium
- The University Of Birmingham, Birmingham, United Kingdom
- Universitair Medisch Centrum Utrecht, Utrecht, Netherlands
- Universitatsklinikum Erlangen, Erlangen, Germany
- University Of Newcastle Upon Tyne, Newcastle upon Tyne, United Kingdom
- Uppsala Universitet, Uppsala, Sweden
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
- Collaborate Project Management Ug Haftungsbeschrankt, Munich, Germany
- Istituto Europeo Di Oncologia SRL, Milan, Italy
- Mindbytes, Merksplas, Belgium
Patient organisations
- European Cancer Patient Coalition, Brussels, Belgium
- International Alliance Of Patient'Organizations, London, United Kingdom
- Muscular Dystrophy Group Of Great Britain And Northern Ireland, London, United Kingdom
Third parties
- International Strategic Marketing Services (Isms), Merksplas, Belgium
Participants | |
---|---|
Name | EU funding in € |
Centre Federal D'Expertise Des Soins De Sante | 252 500 |
Collaborate Project Management Ug Haftungsbeschrankt | 282 500 |
Erasmus Universitair Medisch Centrum Rotterdam (left the project) | 22 513 |
Erasmus Universiteit Rotterdam | 782 257 |
European Cancer Patient Coalition | 223 250 |
Forum Des Patients Europeens | 65 000 |
Instituto Tumori "Giovanni Paolo Ii" Irccs (left the project) | 25 783 |
International Alliance Of Patient'Organizations | 63 173 |
Istituto Europeo Di Oncologia SRL | 496 750 |
Katholieke Universiteit Leuven | 772 759 |
Mindbytes | 209 577 |
Muscular Dystrophy Group Of Great Britain And Northern Ireland | 80 000 |
The University Of Birmingham | 241 750 |
Universitair Medisch Centrum Utrecht | 480 517 |
Universitatsklinikum Erlangen | 230 722 |
University Of Newcastle Upon Tyne | 264 922 |
Uppsala Universitet | 1 455 667 |
Third parties | |
Name | Funding in € |
International Strategic Marketing Services (Isms) | 50 360 |
Total Cost | 6 000 000 |