Patient involvement in the development, regulation and safe use of medicines

by Giuliana Miglierini

The Council for International Organizations of Medical Sciences (CIOMS) has published the CIOMS report on “Patient involvement in the development, regulation and safe use of medicines”.

The report marks an important step forward towards a harmonised approach to patient involvement through the entire medicines’ lifecycle and under all the different perspectives which are part of it. The document is the result of four years of work by the CIOMS Working Group XI on Patient involvement in the development, regulation and safe use of medicines, in collaboration with other relevant stakeholders. Comments were collected during two meetings in Switzerland and Uganda and a public consultation phase.

The report offers recommendations on how to systematically involve patients along the pathway leading from early development and regulatory processing to marketing and monitoring of the safety and efficacy in the real-world contest of use of a medicine. Remaining challenges and practice gaps are also discussed. CIOMS’s secretary Dr. Lembit Rägo gave a presentation at EMA’s Joint PCWP-HCPWP Meeting held in Amsterdam on 4 March 2020.

CIOMS is an international umbrella organisation jointly established by WHO and UNESCO in1949. Members include representatives of the biomedical scientific community, national academies of sciences and medical research councils, jointly committed to develop guidance on health research and policy including ethics, medical product development and pharmacovigilance. CIOMS is an ICH Observer since 2016, and many of its guidelines served as the basis to develop ICH’s ones.

Structure and ethical guiding principles

The CIOMS report consists of eleven chapters and five appendices. After the discussion of the landscape and the guiding principles that should inspire patient involvement, CIOMS has addressed the possible contribution arising from patients aimed to advancing treatments, for each of the steps of development of a new product. Chapter 5 addresses specifically the use of real-world data and evidence generated by patients, a central theme in many new policies in the healthcare sector. The document includes also chapters discussing product labelling and rapid safety communications, as well as additional risk minimisation. Clinical practice guidelines are discussed in Chapter 9. Attention is also paid to low- and medium-income countries and to pandemic considerations.

The rich section discussing case studies includes how to address a medication formulation created to meet patients’ and doctors’ needs and, under the regulatory perspective, the case of EMA’s public hearing on valproate as an example of patient involvement. Partnerships between industry and patient groups for therapy development are also discussed, as well as patients’ engagement in early development plans for a novel treatment. Other case studies address patient involvement in the developing of additional risk minimisation measures and patient activism to counter AIDS denialism and improve access to HIV medicines in South Africa.

The CIOMS report should be read as a pragmatic handbook, recommending ‘best practice’ to serve as a guide, but not necessarily to be entirely adopted. Its contents have been developed on the basis of ethical considerations and fundamental principles of bioethics, highlighting the importance of the opinion of patients as expert partners in the use of medicines. Only patients “can meaningfully contribute their preferences, concerns, understandings, and lived experiences of a medical condition to improve medicine development and use”, states the document.

Another key principle is the respect for persons, which should be always treated as autonomous and making independent decisions, while protection should be provided to persons with diminished autonomy. The result of this vision is a shared decision-making between clinicians and patients, also known as the patient-as-partner approach to medicine. The approach should also include the adequate protection of patients’ personal data and the understanding of their tolerance or acceptance of the risk connected to the use of a certain medicine.

The promotion of wellbeing (beneficence) and the avoidance of harm (nonmaleficence) are other ethic principles inspiring the report. The exercise should take into consideration not only the pharmacological profile of the medicine, but also its possible impact at the logistic, psychological, financial, and social level, as well as opportunity costs. Access to medicines remains a central issue in many instances; to this regard, the report states that “Thus, despite understanding the ethical obligation to provide medicines, individuals or institutions may not necessarily act to fulfil this obligation”.

The concept of “justice” includes modalities for the recruitment of patients for clinical studies, and the fair access and distribution, and knowledge of medicines. Informed consent remains a fundamental principle to be always and freely exercised, while informed assent can apply especially in the case of young children and adults who do not have the legal capability to give consent.

Not only medicines; the patient perspective is fundamental

Contents of the CIOMS report on patient involvement does not apply strictly only to medicinal products, but also to the broader range of products consisting of vaccines, medical devices, drug-device combinations, and diagnostics. All these products are subject to regulatory scrutiny and approval and are aimed to treat or prevent a illness, to make a diagnosis, or to maintain or alter the way the body works.

Patients are identified as the individuals using these products, often flanked and supported by their families, caregivers, patient organisations, and patient representatives. The contribution of patients is deemed essential to correctly identify medical needs on the basis of their daily experience of the health condition. The patient’s perspective can inform early development of new medicines, as well as provide data on safety and efficacy during the post-marketing phase of the lifecycle. All views should be gathered, including the ones arising from often marginalized communities of patients, or those of family carers and other caregivers.

This sort of information may be collected by involvement of patient organisations in the different phases of development and commercialisation, even though there are still some barriers to be overcome. The main one is represented by the cultural shift needed to end seeing patients are passive subjects: they should be regarded as true “research partners” in the development, regulation and safe use of medicines. Other existing barriers include legislative and regulatory burdens as well as language and communication obstacles.

Patient participation to development should be incentivised through reimbursement of time and expenses, suggests the report, while maintaining the independence of patient organisations in order to build a long-lasting and respectful relationship. Digital technologies are suggested as a tool to improve the transparency of communication and to enable telemedicine.

Training should be also provided (for example by patient organisations) in order to optimise patient involvement in the different activities. According to the report, it should include information on medicines-related sciences, ethics of health-related research, clinical trial methodology and interpretation, and medicines legislation and regulation.

Patient involvement in research and development

Patients should be involved in research activity from the very early phases, so to provide their input on candidate medicines. To this instance, key activities may include the definition of research goals and expected treatment benefits, the planning and design of clinical trials and the clear and timely circulation of emerging research information. Preferences of users on formulation and packaging may be also obtained.

The report suggests using well-designed “patient preference studies” as a mean to better understand important elements under the patients’ perspective relevant to their medical conditions and treatment (or prevention).

The regulatory approval process should increasingly take into consideration patients’ opinions on the benefits and risks of a certain medicine, as well as on information arising from the continuous monitoring of side effects. The recommendation is to strengthen the inclusion of patients as members of formal scientific and decision-making committees or working groups on specific scientific aspects of medicine regulation.

Data management and protection and product information

Patient-centred initiatives” are the tool suggested by the CIOMS report in order to better involve patients in the planning and management of real-world data arising from their daily use of medicines. Patients should be enabled to control the actual protection of their data and privacy, and how data are collected, stored, managed and released. Digital technologies represent the preferred tool to reach this objective, and they can also support patients in playing a more active role in the management of their real-world data.

Product information (i.e. the information leaflet contained in each package) is an essential element of a medicine, as it supports its correct use by the patient. The format and clarity of product information has been long debated; the CIOMS report supports the involvement of patients in drafting this information, as a way to improve its relevance and contents. A better compliance to treatment remains a main target, and it may benefit from the information patient scan provide on local customs and traditions, health literacy, and healthcare structures.

Additional risk minimisation measures and safety information

Many innovative therapeutic approaches are characterised by a risk profile significantly higher compared to more traditional treatments. In such instances, the report indicates that the standard information provided to patients may prove insufficient, and additional risk minimization measures may be needed. These measures may create an extra burden on patients, which maybe subject for example to regular testing or need to take extra care. It would be thus important to gather patients’ opinion right from the design and development of the additional measures.

Patients may also contribute to plan how the measures are communicated and put in practice (also using digital technologies where appropriate).

A key pharmacovigilance activity is the rapid dissemination of safety information in case issues arise with the safety of a medicine. To this instance, the report suggests patients to be involved in the decision about issues needing urgent communication, the groups of patients to be informed, and how the information can be designed for patients. Patient organisations can play a central role in the dissemination of such type of information.

Clinical practice guidelines and pandemic preparedness

Patients should be also involved in the development of clinical practice guidelines, aimed to describe how medicines should be used in day-to-day healthcare. This is deemed important in order to overcome the possible bias between patients’ expectations about benefits of the treatment and the consequent acceptance of risks, and the view of these items proper of clinicians and other healthcare professionals.

The importance of patient involvement in the above discussed points has become clear through the experience gathered during the Covid-19 pandemic. The report highlights the importance to consider the lack of knowledge on how new medicines and vaccines are developed and the consequent need to address public concerns about vaccination, the need to deal with misinformation and to provide comprehensive information for patients to make an informed decision.