Developing and evaluating rare disease educational materials co-created by expert clinicians and patients: the paradigm of congenital hypogonadotropic hypogonadism

The landmark 2009 report from the European Organization for Rare Diseases (EURORDIS) brought to light the many challenges faced by patients with rare diseases [1]. Delays in diagnosis, difficulty finding information about their condition and inadequate access to expert care are frequent patient experiences. Indeed, some have posited that living with a rare disease places one in the realm of health disparities [2]. Physical and psychological morbidity can be significant and feelings of isolation and powerlessness can further undermine quality of life [3]. Importantly, potential means to overcome these challenges include using the internet to connect dispersed patients with expert care and community engagement to help empower patients who feel marginalized by the healthcare system [4‐6].

One such rare disorder is congenital hypogonadotropic hypogonadism (CHH, ORPHA174590). Based on a study of French conscripts, CHH occurs in approximately one in 4,000-10,000 [7]. It is clinically characterized by incomplete (or absent) puberty and infertility resulting from insufficient secretion or action of gonadotropin releasing hormone (GnRH) - the master hormone of the reproductive axis [8]. Genetic defects that affect olfactory axon and olfactory bulb development, thus leading to absent or defective sense of smell (anosmia or hyposmia), usually also affect the migration of neuroendocrine GnRH cells from the nose to the brain during embryonic life, thus leading to CHH. This condition is known as the olfacto-genital syndrome or Kallmann syndrome (ORPHA478). Some genetic and phenotypic overlap may exist between isolated CHH and Kallmann syndrome, yet patients with this syndrome are much more likely to exhibit additional non-reproductive phenotypes (i.e., skeletal defects, renal agenesis, cleft lip/palate, deafness, etc) than normosmic CHH patients. In the context of an international network of leading clinicians/geneticists/researchers focused on CHH [9], we have previously developed patient partnerships and conducted a needs assessment that leveraged engagement with patient support groups, social media and online data collection [10]. In parallel, we developed a web-based platform [9] with resources for patients to find expert clinicians and peer-to-peer support. Additionally, consensus guidelines for the diagnosis and treatment of CHH were created using an evidence-based approach [8].

Engagement and co-creation have been effectively used in diverse fields including business, design and computer science (i.e. user-centered design) as a means to spur innovation, adoption and foster sustainability [11, 12]. Therefore, the aim of the present study was to partner clinical experts and patients to co-create high-quality patient education materials (PEM) that respond to the issues and questions most important and relevant to patients. Secondary aims included evaluating the readability of the PEM and end-user acceptability (i.e. understandability and actionability) as well as to disseminate these materials widely across different countries and cultures.

The aim of this study was to engage patients and co-create PEM that respond to what matters most to patients. Subsequently, we evaluated the readability and end-user acceptability of the PEM and sought to widely disseminate the translated PEM across different countries and cultures. Patients living with a rare disease face health disparities [2] and patient engagement has been identified as potential means to empower this patient population [4‐6]. Interestingly, patient engagement has recently been gaining attention in the context of orphan drug development [23]. However, the extent of patient engagement varies widely. A 2014 systematic review of patient engagement for research on rare diseases found engagement is typically unidirectional - involving patients in consultative roles and rarely in creative aspects or in terms of dissemination [24]. The present study is unique in that we used a participatory process to co-create PEM with patients; we then evaluated the PEM produced by this collaboration, and worked with patient groups to facilitate dissemination to the largest possible audience.

We previously partnered with online patient community leaders to identify the unmet health and informational needs of patients with congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome [10]. In the present study, the partnership was more clearly bi-directional as patients were not simply providers of opinions; rather they contributed directly in co-creating the PEM in an iterative process. Notably, patient knowledge and expertise emerges from the day-to-day experiences of living and coping with a rare condition and therefore is inherently different from the expertise of healthcare professionals [25]. Recently, a study examining online exchanges among patients with rare adrenal disorders found that information and support were central elements in peer-to-peer exchanges [26]. Moreover, the authors noted that patient-centered care could be enhanced by better integrating patient knowledge with the care provided by professionals. In the present study, developing the PEM was a true partnership that recognized patient expertise as unique and complementary to expert clinician knowledge. We believe that this co-creation contributed to the high acceptability ratings by patients.

This evaluation process of the co-created PEM has limitations. The evaluation was only conducted on the English version. As such, the findings are not completely transferable to the other translated versions despite the inclusion of patients in developing some of the translations. Moreover, the additional validation step of back translating the other versions was not conducted and this could be viewed as a limitation. We only assessed readability once the materials had been finalized, not during the development process. In future studies, this testing could be incorporated earlier in the development process to improve the reading level of developed PEM. While the evaluation was overwhelmingly positive and a fairly sizeable sample was reached (for a rare disease population), the patients completing the evaluation were quite well-educated and exhibited high levels of health literacy. Accordingly, our ability to draw inferences to a broader population of lower literacy patients is limited. This may reflect a bias of using a web-based survey - as perhaps those using the web may have higher literacy levels. However, recruiting sufficient numbers of patients for rare disease studies has been a long-standing challenge [27, 28]. Therefore, we used a web-based approach to overcome this barrier but note that such an approach entails a potential risk of bias.

The Pew Foundation’s published report on health and the internet indicates that patients living with a rare disease are internet power users who are most likely to seek information about their condition online and find support from other patients using social media [29]. Based on our previous success combining patient partnerships and social media for the online needs assessment [10], we employed a similar approach in the present study to reach a relatively large sample (n = 63) over 8-weeks. These experiences suggest that web-based platforms are an effective means to reach and connect rare disease patients. Thus, the opportunities afforded by the internet and social media may provide novel avenues for crowdsourcing solutions as well as offering a shared venue for either clinician- or patient-led collaborations to improve quality and add value to the healthcare system [5, 30]. The European Union Committee of Experts on Rare Diseases (EUCERD) recommendations for Centers of Expertise underscore the importance of collaboration with patient organizations to provide information that is at once accessible and adapted to patient needs [31]. For many rare diseases, such as CHH/Kallmann syndrome, formal organized patient support organizations do not exist. As such, web-based approaches and social media provide a critical means to broadly reach patients, identify priorities and incorporate their perspectives and knowledge into care. This may be particularly advantageous in light of the movement to form European Reference Networks for rare diseases [32, 33].

The final step in this co-creation process was to engage in bi-directional dissemination. This has been identified as a shortcoming in much of the patient engagement research conducted in the context of rare diseases [24]. Through the work of members of the Network and patients alike, materials were adapted and translated into 20 languages by native speakers. This collaborative process is essential for ensuring that information provided to patients is culturally adapted and sensitive – a key element for Centers of Expertise [31]. In parallel to traditional healthcare professional outlets (e.g. scientific meetings, peer-review publication) patient participants are distributing materials directly to other patients via social media and postings on centralized patients sites [15]. The co-created PEM (in multiple languages) is a critical component of the list of patient resources available on the website of the European network comprising a virtual empowerment toolkit for patients and families [9]. Available information includes listings of international specialized referral centers, genetic testing labs, clinical trials, and peer-to-peer support as well as a portal for a patient registry. We are utilizing both professional-oriented avenues and more patient-oriented social media outlets to hopefully reach unprecedented numbers of patients and clinicians and overcome traditional roadblocks of implementation into practice [34‐36].

Partnering with patients enabled co-creation of high-quality PEM while social media and web-based data collection facilitated timely evaluation by a dispersed patient population. We believe that partnering with expert patients was an empowering experience and provides valuable contributions for developing patient-centered approaches to care. We envision this work will serve as a roadmap for those wishing to engage in a co-creation process and will help inform projects aimed at improving care for patients living with a rare disease.