Patient Experience Data in Rare Diseases

Article based on a poster presented at the 11th European Conference on Rare Diseases and Orphan Products (ECRD), 27. June to 1. July 2022, titled:

Innovation in the Science of Rare Disease Patient Input:? Mixed-Methods Approaches

The potentially severe quality of life (QoL) impact on persons, families and caregivers living with rare diseases (RDs) is well recognized (1). RDs are often complex, multisystemic, chronic and as most individuals will not be cured in their lifetimes, identifying ways to improve QoL is crucial to patient-centred care (2).

However, most orphan medicinal products (OMPs) have not demonstrated the ability to improve QoL, and clinical studies in rare conditions are often criticised for not incorporating those outcomes that matter most to patients (2, 3).

Patient reported outcomes (PRO) research remains particularly challenging in small, heterogenous as well as paediatric populations (2, 4). Orphan drug PRO-based labels are few and far between, and the impact of PRO data in health technology assessment and pricing, while recognised as relevant, has been suboptimal (5).

Decision-makers cite fundamental difficulties with PRO data, including inappropriate, non-validated patient reported outcome measures (PROMs), lack of content validity, missing, inconsistent, uninterpretable data, and failure to meet thresholds for Minimal Important Clinical Difference in response to therapy (3, 5).

Generic PROMs are not sensitive to the multifactorial specificities of RDs and while disease-specific instruments are sensitive, they do not exist for most conditions (5).

Aiming to address the current limitations of traditional quantitative analyses, mixed-methods approaches combine quantitative and qualitative patient lived experience data (QAL-LE) (4, 6). Endorsers of this approach include the FDA (Patient Focussed Drug Development), the EMA (Patient Engagement Framework), and the International Rare Disease Research Consortium (IRDiRC) (7, 8, 9).

Quantitative/qualitative mixed methods explicitly incorporate direct patient insights, and therefore necessitate the fusion of Patient Experience Data (PED) generation with patient engagement. This critical aspect is emphasised by the new PED Navigator developed by the Patient Focussed Medicines Development (PFMD) initiative.

Patient Engagement is essential in order to build a patient-centred, comprehensive and robust data resource that can be used by all stakeholders in the health ecosystem. Specifically, patient engagement is needed to help with the co-creation and design of PED and also to contextualise and add meaning to the collected Patient Experience Data.

Quoted from: The Global Patient Experience Data Navigator (PFMD, 2022)

Further innovation in science of patient experience data will involve the development of novel multi-domain (composite) rare-disease-specific endpoints, prospectively linking clinical outcomes with validated quantitative PROMs and thematic analysis of QAL-LE data, providing a contextual, individualised, and detailed understanding of the disease burden, ultimately resulting in a truly patient-centred, holistic assessment of the benefit-risk of experimental therapy within RD clinical trials (7, 10, 11, 12, 13). See Figures 1 and 2.

These are hopeful advances to further enhance the science of patient research, with the aim of supporting the development, approval, and access of innovative OMPs, which effectively address those unmet needs that matter most to a broad group of heterogeneous RD patients (see the summary in Figure 3).

References

1. EURORDIS, Rare disease patients' opinion on the future of rare diseases, A Rare Barometer survey for the Rare 2030 Foresight Study, June 2021,?https://download2.eurordis.org/rbv/rare2030survey/reports/RARE2030_survey_public_report_en.pdf ??(accessed March 2022)
2. KR Bogart and VL Irvin, Health-related quality of life among adults with diverse rare disorders, Orphanet Journal of Rare Diseases (2017) 12:177 DOI 10.1186/s13023-017-0730-1
3. YD Hong et al, Patient-Reported Outcomes in Orphan Drug Labels Approved by the US Food and Drug Administration, VALUE HEALTH. 2019; 22(8):925–930
4. S Lanar et al, Understanding disease symptoms and impacts and producing qualitatively-derived severity stages for MPS IIIA: a mixed methods approach, Orphanet Journal of Rare Diseases, (2022) 17:75,?https://doi.org/10.1186/s13023-022-02208-w
5. A Whittal et al, The Use of Patient?Reported Outcome Measures in Rare Diseases and Implications for Health Technology Assessment, The Patient - Patient-Centered Outcomes Research (2021) 14:485–503?https://doi.org/10.1007/s40271-020-00493-w
6. M Bharmal et al, How to address the challenges of evaluating treatment benefits-risks in rare diseases? A convergent mixed methods approach applied within a Merkel cell carcinoma phase 2 clinical trial, Orphanet Journal of Rare Diseases (2018) 13:95?https://doi.org/10.1186/s13023-018-0835-1
7. Patient-Focused Drug Development: Methods to Identify What Is Important to Patients, Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders, FDA, February 2022,?https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-focused-drug-development-methods-identify-what-important-patients ??(accessed March 2022)
8. European Medicines Agency (EMA), Patient Engagement Framework (January 2022) https://www.ema.europa.eu/en/documents/other/engagement-framework-european-medicines-agency-patients-consumers-their-organisations_en.pdf
9. International Rare Disease Research Consortium (IRDiRC), Orphan Drug Development Guidebook,?https://irdirc.org/orphan-drug-development-guidebook-materials/ (accessed March 2022)
10. J Sibeoni et al, A specific method for qualitative medical research: the IPSE (Inductive Process to analyze the Structure of lived Experience) approach, BMC Medical Research Methodology, (2020) 20:216,?https://doi.org/10.1186/s12874-020-01099-4
11. PK Tandon and ED Kakkis, The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases, Orphanet J Rare Dis (2021) 16:183,?https://doi.org/10.1186/s13023-021-01805-5
12. P Harmatz et al, A novel Blind Start study design to investigate vestronidase alfa for mucopolysaccharidosis VII, an ultra-rare genetic disease, Molecular Genetics and Metabolism 123 (2018) 488–494,?https://doi.org/10.1016/j.ymgme.2018.02.006
13. L De Rosa et al, Hologene 5: A Phase II/III Clinical Trial of Combined Cell and Gene Therapy of Junctional Epidermolysis Bullosa. Front. Genet. 12:705019 (2021) doi:10.3389/fgene.2021.705019?

Correspondence

David Schwicker, Principal, ORPHA Strategy Consulting, Basel, Switzerland, Mobile Phone: +43 676 362 9571, [email protected] ? www.orphastrategy.com ?