For many people who work in drug development, medicines regulation or life-cycle management, improving the life of patients is the reason we get out of bed in the morning. For numerous patients there are therapies that improve their lives and control their diseases. However, I have seldom heard any patient say that their new medicine is fantastic and controls all their symptoms. Why is this?
Developing a new medicine is expensive and time consuming. DiMasi et al, from the Tufts Center for Study of Drug Development, estimated that the development cost (including failures and capital costs) per new successful prescription drug was over $2 billion.[1]. Drug development is aimed at providing evidence for regulators to allow the drug to be authorised: namely that the potential benefits outweigh the potential risks in the approved indication.[2] However, the endpoints used for efficacy analyses are frequently not those that a patient might necessarily choose.
During a clinical trial for a new treatment for Duchenne’s Muscular Dystrophy a patient’s carer realised that the drug was having some effect when the young man he was looking after was able to remove the top of a beer bottle by himself – something he had not been able to do before the new treatment! Although anecdotal, this shows the disparity between what might be of importance to a patient and the formal endpoints usually studied in clinical trials.
The treatment of multiple sclerosis (MS)has been dramatically changed by the development of biological products which effectively slow the progression of the disease. Despite the many different compounds available, MS patients say that none really reduces the fatigue that is part of the disease. So, treatments can be highly efficacious but fail to address a symptom which has an important effect on patients’ lives.
This is why the recent publication by the Council for International Organizations for Medical Sciences (CIOMS) is so important. Published in September 2022, the report on “Patient involvement in the development, regulation and safe use of medicines” provides guidance for best practice on patients as partners during drug development and subsequently.[3] The CIOMS report describes and promotes the idea that patients should be involved throughout the medicine’s life – from development, through authorisation to ongoing safe use in everyday life.3
“Patient Centricity” has been a buzzword in the pharmaceutical industry for around a decade, but the reality is that few companies or research institutions regard patients as true partners in drug development and for some, the role of the patient is solely as a research subject and contributor of data. This is missing a huge opportunity to engage the person who knows most about how it is to live with a disease, in the research process. The CIOMS guidance seeks to change this.
Right at the beginning of the drug development process, patients can provide invaluable insight into the effect the disease has on them and what the ideal medicine could achieve. Clinicians and patients can describe the natural history of the disease so that endpoints that are relevant to patients are chosen to prove efficacy. Considerations on formulation and packaging can be discussed early on so that any problems can be identified early.
Patients can play an important role in clinical trial design. This can range from defining the research questions, advice on reducing the burden on patients to suggesting sites and incorporating patient reported outcomes.
Regulators in many jurisdictions have already seen the value of patient input into regulatory decision making. The European Medicines Agency (EMA) has patient representatives on most of its Committees and the Japanese regulatory scientific committees pose specific questions to patients during the review process. The FDA holds public meetings that systematically obtain the patient perspective on specific diseases and their treatments and there is a Patient Engagement Advisory Committee which provides advice on medical devices.[4]
Patients can provide input to regulators either at the time of authorisation or post-authorisation on how specific risks are perceived and the benefit-risk trade-off. During the 2016 referral on natalizumab, patients were consulted on the feasibility and burden of requiring more frequent magnetic resonance imaging to allow early detection of progressive multifocal leukoencephalopathy.[5]
All medicines have risks and in most regulated jurisdictions, there are required activities to reduce the risks. These range from routine, in the form of product information for both patients and healthcare practitioners, to more complex additional risk minimisation activities. In the EU, there is a legal requirement for patient information, and the packaging, to undergo testing by patients.[6]
Patients can play an invaluable role in designing additional risk minimisation measures. They can provide advice on what are the key things that a patient needs to know about a medicine. They can suggest the most appropriate format for educational materials, suggest wording and can also test draft prototypes to see how understandable they are. They are also key in adapting global risk management programmes to ensure acceptability and feasibility in a local country.
The CIOMS report provides an extensive overview of how patients can be involved throughout the life-cycle of a medicine. Whilst not everything in the guidance will be implemented by all companies immediately, it provides a pathway towards incorporating patients as partners in all aspects of medicine development and use. Making the patient the centre of, and a partner in all we do will result in better medicines, better drug development and safer use.
[1] DiMasi .Tufts Center for the Study of Drug Development Briefing “Cost of developing a new drug. November 2014
[2] Blackburn SCF, Raine JM. The Principles behind risk management in the European Union. Mann’s Pharmacovigilance Third Edition 2014 Ed EB Andrews, N Moore.
[3] Patient involvement in the development, regulation and safe use of medicines. Report of the CIOMS Working Group XI. https://cioms.ch/publications/product/patient-involvement/ . https://doi.org/10.56759/iiew8982
[4] FDA Patient Engagement Overview https://www.fda.gov/patients/learn-about-fda-patient-engagement/fda-patient-engagement-overview accessed January 27th 2023
[5]European Medicines Agency Article 20 referral Assessment Report on Tysabri EMA/PRAC/171485/2016.
[6]Directive 2001/83/EC of European Parliament and of the Council of 6th November 2001 on the Community code relating to medicinal products for human use as amended. Articles 59(3) and 61(1).
