Engaging patients in the work of decision makers at national and international level

Patient supported proposals for improvements may complement those of the national competent authorities and health care professionals and can and have been documented (Hertel et al., 2019; Bombard et al., 2018) to be of truly great value. In addition to national health authorities, patient involvement can be of benefit to regional or international health related bodies including the World Health Organization (WHO). Patients’ views and perspective can greatly facilitate the better understanding of the hugely heterogeneous unmet needs of patients with different chronic conditions, in a country, across countries, across different Regions of the world. WHO and other official health related bodies are in need of reliable, real world data to tailor more effectively their work and actions including revisiting general health or disease specific resolutions and recommendations with the support and interaction of their member states. Data on policy related outcomes cannot be obtained in the absence of patients’ involvement and without truly ‘capturing’ the patients’ perspective and position.

The example of the European Union (EU)

For many years now, in Europe a very strong effort has been undertaken to support Rare Diseases through a number of European Union (EU) official Recommendations, Regulations, Directives, and Decisions. All of these include as a prerequisite for their preparation and later implementation at national level, the full and meaningful engagement of the patients and the clear expression of their position. In fact, the empowerment and recognition, by the European Community (EC), of the added value involved in addressing the huge unmet needs of Rare Diseases (RDs) (Aymé, Kole & Groft, 2008) came initially in the 1990s from the active, persistent and very well-structured engagement of the RD patients themselves through their European umbrella association, the European Organisation for Rare Diseases (EURORDIS) (De Santis et al., 2019). The methodology used by the EU in interacting and collaborating with the patient, and the weight given to the patient’s position could indeed constitute a fine example of how official stakeholders can truly involve the patient’s perspective beyond Europe and across the world (TNS Qual+, 2012).

Where and how patients can be engaged - examples

In another field, engaging the patient’s perspective in developing new or in reforming existing official legislations and policies relevant mainly but not confined to health, social care and education, has proved, in every case and in every country, that has ‘allowed’ or encouraged such practices, extremely beneficial. The involvement of patients within the health care provision has been in place for quite a long time in Cyprus, with the Pancyprian Thalassaemia Association on the lead since the 1960s. Patient involvement (PI) however, was made mandatory in Cyprus in 2016 through a new law [46(I)/2016)] that officially recognised patients as a valuable and equal stakeholder to the Government. This has allowed their full and active engagement in almost every step of the very extensive health care reforms the Cyprus Government undertook to implement in recent years. The contribution of the patient’s engagement has been extremely valuable and greatly appreciated by Government and all other official stakeholders involved in this reform acknowledging the very fact that Cyprus was committed to establishing a new truly patient centred health care system.

Patients in many countries today are involved at different levels in national health committees that may be disease specific and/or public health/health care system related.

The involvement of patients living with haemoglobin disorders in some countries across the world has resulted in the inclusion of their condition in a number of important disease specific social, and where patients felt essential, disability oriented policies/legislations including (and not confined to) early retirement, travel remuneration, quotas for university admission and employment and many others, different in each country.

The engagement of patients in many, if not all, decision making committees of the EC/EU is mandatory and has thus contributed significantly to having truly patient centred decisions, recommendations, directives and regulations. The participation of patients is clearly described in most of these and an illustrative example is the European Directive (transposed into the national legislation of every EU member country) 2011/24/EU (and its two Addenda 2014/286/EU and 2014/287/EU) for safeguarding the rights of patients with RDs in obtaining cross-border healthcare. In this, the establishment of the European Reference Networks (ERNs) for RDs (including rare anaemias and haemoglobin disorders) constitutes a key recommendation and the full patient’s involvement is a prerequisite.

One must not ignore that further to the patient’s wellbeing and social integration, which constitute the two major goals for an effective health and social care system in a country, practices which involve the patient’s perspective contribute greatly to the system’s sustainability through for example their participation in Health Technology Assessment (HTA) bodies (Single et al., 2019) and which in many instances, has been pivotal for price negotiations of many available expensive drugs.

A 2019 Deloitte Report on patient access to innovative medicines in Europe (Deloitte Centre for Health Solutions, 2019), points out that early dialogue and partnership with regulatory and important stakeholders including patients can provide a number of benefits to all and can aid pharma product pricing. Similarly, outside Europe, pharma organisations, more and more in current years, are engaging with payers and patients earlier, in much more constructive, collaborative and valuable ways. Such engagement helps pharma develop products that meet the priorities of the health care system and the unmet needs of patients and importantly enter into pricing negotiation to model and discuss a variety of potential contracting solutions to achieve market access. New innovative drug products and therapies need to be made available and to reach the patients in a timely way particularly those with RDs.

European based pharmaceutical industry has attempted in 2015 a qualitative interview study to identify the value and challenges of Patient Involvement (PI). In the conclusions of this work, many were uncertain about when, how and which patients to involve (Parsons et al., 2016).

Patients and the public’s lack of knowledge and interest in medicines R&D, and the pharmaceutical industry’s lack of knowledge, interest and receptivity to PI were believed to be key challenges to increasing PI. Interviewees also believed that relationships between the pharmaceutical industry, patient organisations, patients and the public needed to change to facilitate PI in medicines R&D. Existing pharmaceutical industry codes of practice and negative media reporting of the pharmaceutical industry were also seen as negative influences on these relationships.

On the same argument, the authors of a 2018 publication (Levitan et al., 2018) argue that risk-adjusted financial models can actually assess the impact of patient engagement particularly in the context of clinical trials. A combination of empirical data and subjective parameter estimates shows that engagement activities with the potential to avoid protocol amendments and/or improve enrolment, adherence and retention may add considerable financial value.

In the context of the new Regulation (EU) NO. 536/2014 for clinical trials of medicinal products for human, there is (in addition to many other benefits) a significant increase in transparency on clinical trial data and data generated with a greater involvement of the public and patients with the mandatory introduction of a patient into the testing teams and the publication of a final report in language (Tenti et al., 2018) dedicated to the public and not the workforce.

In more recent years, patients’ involvement along the whole chain of Research and Drug Development (R&D) has been greatly strengthened and placed on a more professional basis by the two major drug regulatory authorities including the European Medicines Agency (EMA), National Institute for Health and Care Excellence (NICE) and the Food and Drug Administration (FDA).

There is unequivocal evidence collected by EMA (EMA, Stakeholders & Communication Division, 2014) and FDA on the valued contribution of patients’ views and involvement in medicines R&D. Already EMA, has taken significant steps in this direction through a number of its committees, in which patients participate including the Committee for Orphan Medicinal Products (COMP), Paediatric Committee (PDCO), the Committee for Advanced Therapies (CAT) and Pharmacovigilance Risk Assessment Committee (PRAC). In these bodies, patients’ representatives may assume the status of full members including having the right to vote for the drugs’ assessment and approval processes. Patients involved however, should be free from any conflict of interest and no association at any level with the pharma industries so as to ensure the unbiased nature and full transparency of the approval process. In 2018, EMA reported that one in five scientific advice procedures involved patients and the scientific committee members (SAWAP) considered that in almost every case, patients provided an added value to the scientific advice and in about one in four cases, the scientific advice recommended that the development plan be modified to reflect patient advice (EMA, 2019).

EMA is now proposing the fostering of earlier contact with patient/consumer organisations. It proposes to reach out to patients at the start of the evaluation of new Marketing Authorisation Application (MAAs) so that patients can share their experience and concerns about their condition(s) and key aspects that are important for them in order for this to be taken into account in a timely manner during the assessment process. Aspects that are of particular to patients/carers such as quality of life, standard treatments on how acceptable they are, how these interfere with their lives, therapeutic unmet needs, what their expectations are with regards to the benefits they hope to have, the level of side effects they would consider acceptable. It will greatly facilitate the better understanding of whether there are large differences between groups of patients/carers of the same disease area or concerns are similar across the condition and certainly to note anything else that patients/carers feel is important for EMA to know. (EMA/372554/2014-29/11/2020).

Similarly, and along the same lines, earlier in 2012, as part of the reauthorization of the Prescription Drug Use Fee Act (PDUFA V), the US FDA (Perfetto et al., 2015), established a programme to help ensure patients’ experiences, perspectives, needs and priorities are captured and meaningfully incorporated into the development and review process. This was formalized as Patient-Focused Drug Development (PFDD). A number of activities and meetings are involved in this novel approach so as to gather input from patients who are willing to share their personal experiences of living with a disease or condition.

Patients and patients’ organisations should be meaningfully engaged at all stages from defining research priorities to trial design, review of proposals, trial implementation and participation. And indeed, this has become, especially in the last decade, a routine and in most cases a mandatory practice both by the academic research community and the industry.

In this context, published literature even provides description of a possible road map of patient involvement (PI) across the whole spectrum of R&D life cycle (Figure 2) and key areas and opportunities for PI within early stage are identified (Geissler et al., 2017). In the course of such involvement, both the patients and Research scientists gain a number of different for each party benefits, some of which are mentioned below including for patients (A) and Research (B):

Figure 2

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Gaining knowledge and research skills; Increased understanding of the nature and purpose of a clinical trial;

Practical roadmap for patient involvement in medicines R&D. DIA Therapeutic Innovation & Regulatory Science 2018. Vol 52(2) 220-229. (With permission)

It is true that many on the development side often fail to take into account real-world challenges when developing a clinical trial. They are more interested in determining the efficacy and safety of a drug rather than taking into consideration quality of life issues. The contribution of the patient’s perspective is in more recent years not only recognized but very importantly sought after and considered essential. The collection of real patient data, for example is a prerequisite in the context of certain types of authorization licenses granted by EMA and FDA and mainly regarding innovative drugs/therapies, which may be granted accelerated procedures or authorization under exceptional circumstances or conditional marketing authorization.

These types of licenses are granted to address unmet medical needs of patients. Either for patients with unmet needs to facilitate their accelerated access to a new medicine or because the drugs cannot be approved under a standard authorization as comprehensive data cannot be obtained either due to the rarity of the disease, or because there are gaps in the scientific knowledge. These drugs are subject to specific post-authorisation obligation and monitoring and they are authorized on the basis of less comprehensive data than normally required to address unmet medical needs. Although the applicant needs to present data that indicate that the medicine’s benefit outweighs its risk, the applicant should be in a position to provide the comprehensive clinical data in future.

For such data to be collected, the continued, well-structured and coordinated patient engagement is absolutely essential. PI has steadily gained increased recognition, not only by the EU and the WHO which had since the early 1990s official collaboration with patient oriented Non-Government Organizations (NGOs), but also by an increasing number of national health authorities across all regions of the world. An expert patient advocate Jan Geissler, leading the EUPATI (European Patients’ Academy on Therapeutic Innovation, an excellent educational initiative originally launched by the Innovative Medicines Initiative (IMI) and hosted by the European Patients’ Forum (EPF), believes that “involving patients while designing trials and developing drugs will help so that non-scientific factors that are still crucial to evaluating a drugs’ efficacy can be taken into consideration” (Chakradhar, 2015).

Engaging patients in educational programmes

Significant progress has also been made by medical bodies with respect to the recognition of the value of engaging patients in their programmes, mainly educational ones. The European Haematology Association (EHA) is a fine example in the case of haematological diseases including haemoglobin disorders. Since 1992 EHA has promoted, in a very structured way initially with scepticism and reservations to a certain level, a patients’ advocacy group (TIF participates), the work of which through the years has proved to be an added value to the work of EHA. In the 2018 the ‘EHA Research Roadmap on Haemoglobinopathies and Thalassaemia: An update’, includes “the development of Patient Reported Outcomes (PRO) tools to support the work and collaboration with patient organisations” amongst its key recommendations (Iolascon et al., 2019). Such collaborations have developed through the years or are in development with other medical orientated groups including the International Society of Blood Transfusion (ISBT), the European Blood Alliance (EBA the European Association for the Study of the Liver (EASL) just to mention a few relevant to the work of TIF.

Acknowledging the value of patient outcome in healthcare delivery

Patient reported outcomes is a major and invaluable tool developed to ‘capture’ in a more structured ways patients’ information and views that can be appropriately analysed and assessed in order to better understand their needs and expectations for the health, social and other specialised care they are receiving (Lavallee et al., 2016).

Collecting patient experiences and expectations in routine care is crucial in developing services that focus on patient centred care. Often, changes with regards to service provisions are made by those who have the best intention but no true or life experience of the condition. As a result, their perceived goals as to what their patients want may differ to that of those with live with the condition. Having pragmatic insights into patients’ experiences of symptoms, quality of life, values, preferences and goals in life are essential in providing any health care service that is effective for a medical condition.

Previously embraced in the research realm, patient-reported outcomes have started to play a role in successful shared decision making, which can enhance the safe and effective delivery of health care. Present and future challenges need to be analyzed and examined so as to provide the opportunity to health care systems to maximize the use of patient-reported outcomes in the clinic/hospital.

Reported outcomes as a tool, therefore, can be both disease specific or general health care oriented one. It can play a role in shared decision making which can in turn enhance safe and effective delivery of healthcare. Emerging practices consequent on patient reported outcomes have provided value to both patients and clinicians and have improved care services albeit this tool is not to date extensively applied.

The key…

However, the key to meaningful and productive patient involvement lies largely on the very good knowledge and often relevant experience that the patient has in the particular area he/she is assigned to interact. In this context, European umbrella organisations such as the European Patients’ Forum (EPF), the European Organisation for Rare Diseases (EURORDIS) and a number of disease specific organisations at the European level have been very actively involved in developing very comprehensive educational programmes for patients with different diseases on a variety of health, drug and other research related topics in collaboration with experts and other stakeholders including the industry. These programmes aim at building a competent patient community that is knowledgeable enough to interact productively and advocate effectively for the rights in quality and safe care at all levels and importantly at decision-making level at country and European levels.

TIF, the International Alliance of Patients’ Organizations (IAPO) and other international disease specific organisations on the other hand have been struggling for decades now in the international arena and have been, and still are, actively involved in safeguarding patient safety, drug and blood safety and equity of all to quality health and social care. TIF, particularly since its establishment in1986, with the development and continual updating and upgrading of its educational programmes aims to strengthen the knowledge of patients across the world and ‘transform’ them to valuable and equal partners at the decision making level.

TIF in this context has developed since 1989, an educational programme which is constantly strengthened and is based on three pillars:

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Preparation, publication, translation (into many languages) and distribution of educational and informational material: books/factsheets etc.; The organization of events: workshops, seminars, conferences, symposia, meetings, courses, fellowships;

In addition, in more recent years, TIF established in 2017, the TIF Patient Advocacy Group (T-PAG) comprised of 198-member patient advocates from 62 countries. Many of these have developed adequate competency to actively advocate and interact productively at different levels of decision making at national, regional or international level and still many others are under training and working mostly at national level. The vision of TIF being to ‘create’ a large group of competent patient advocates across countries and Regions of the world to make the voice and position of the patients with haemoglobin disorders when involved, strong and effective.

Below Figure 2 and Tables 1 & 2 describe TIF’s Patient Advocacy Groups (TIF PAGs) project, its structure and membership (Figure 2), the eligibility criteria for the inclusion of patients in the PAGs (Table 1) and briefly their role as TIF PAG members (Table 2) and TIF’s responsibilities in supporting their educational work and meaningful engagement at all levels (Table 2).

Table 1

Table 2

Figure 3

TIF and its work on PI

TIF, since its establishment in 1986, has strongly advocated for patient engagement and respect to the patient’s perspective and position and has involved patients in every aspect of its work and activity at all levels. TIF was amongst the first, it not the first patient organization, that was organizing annually, since 1989, patient associations meetings, what we today described as as ‘training programmes’ for improving patients’ knowledge, skills and competencies for advocacy.

The national Thalassaemia Associations in UK, Italy, Greece, Cyprus and USA, founding members of TIF, are fine examples in exercising very active PI since the very early years of their establishment in the 1960s/1970s and it is indeed the successful outcome of such involvement that gave TIF the strength and empowerment to extent this work across the world. Today many patients through the 137 National Thalassaemia Associations in 59 counties members of TIF are actively involved at national and some at Regional level and the outcomes of such involvement as reported to and evidenced by TIF, are very encouraging and in many cases truly impressive.

Engagement of patients has been happening for many years now in the field of haemoglobin disorders, albeit in a less structured way and with greater scepticism and slower pace in many countries outside Europe and other Western countries and the PI and its achievements in some of the developing countries are indeed quite remarkable. Patients must however continue to act through the strong, united voice of their national associations which bear the responsibility to build up educational programmes for strengthening the knowledge and advocacy skills of their patients, some of whom will reach that advocacy competency that would allow their interaction at national or international decision making level.

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TIF as a patients umbrella association, through it work has achieved the establishment of very important collaborations with valuable stakeholders whose support is substantial for achieving its mission, including: the World Health Organisation (WHO) with (more...)

In addition, throughout the years TIF has achieved to establish valuable collaborations and to network productively with over 200 medical/scientific national and international experts and with almost every relevant medical/scientific association or body. Importantly, TIF has gained the respect of competent national health authorities in more than 60 of its member countries around the world, with many of which, it works in the context of special collaborations and/or official agreements.