The 28^th of February marks International Rare Disease Day, which aims to raise awareness and generate change for the 300 million people worldwide living with a rare disease. Throughout this blog, we will discuss the most recent advances in the rare disease landscape from the development of government frameworks, launch of diagnostic services and funds enabling early access to treatment to updated process for approving medicines to be offered by the NHS. In addition, we will be sharing how real-world evidence (RWE) can play a pivotal role in facilitating the approval of ground-breaking therapies for rare diseases.

Rare diseases are a broad range of conditions with a prevalence of 1 in 2,000 people in the general population, equalling approximately 263 – 446 million people globally and 3.5 million in the UK^(1,2), or more patients than all cancers combined⁽³⁾. Numerous factors can lead to a rare disease diagnosis, however around 80% of those diagnosed are caused by genetic factors with a high percentage starting in early childhood⁽⁴⁾. A rare disease diagnosis carries a lifelong sentence of struggle for patients and their families as these diseases are rarely curable and more than 30% of children with a rare disease die before their fifth birthday⁽²⁾. Therefore, government, researchers and pharma companies have committed to working on improving the diagnosis, treatment, and healthcare policies for these patients.

Over the years, Patient Advocacy Groups (PAGs) and Non-Government Organisations (NGOs) have been vitally important in  raising awareness and advocating for global health prioritisation as well as taking part in the launch of funding models for Rare Diseases and setting up patient registries suitable for research purposes⁽³⁾. In 2019, Department of Health and Social Care (DHSC) worked with rare disease patient organisation stakeholders as well as other bodies such as NHS England, to develop a national survey with the aim of identifying the major challenges people living with a rare disease face. The survey was completed by five key rare disease stakeholders including people living with a rare disease, their families or carers, clinicians, and researchers. The outcomes from this survey  formed as the basis for the development of the UK Rare Diseases Framework which identified four priority areas⁽⁵⁾:

• Priority 1: Helping patients receive a final diagnosis faster
• Priority 2: Increasing awareness of rare diseases among healthcare professionals
• Priority 3: Better co-ordination of care between healthcare professionals and patient’s families
• Priority 4: Improving access to specialist care, treatments, and drugs

For the purposes of this blog, we will focus on priority areas 1 and 4 and discuss how these have been addressed so far.

The NHS Genomic Medicine Service (GMS) was launched to address the biggest reported challenge “getting the right diagnosis” for rare disease patients who can spend years seeing multiple specialists and undergoing several tests before receiving a formal diagnosis. Not only, does this lead to frustration for patients, but it has also been estimated to cost the NHS an excess of £3.4 billion⁽²⁾. With 80% of rare diseases having a genetic component, this service which offers whole genome sequencing routinely for suspected rare disease patients have allowed for accurate diagnosis. Due to the rapid progress of rare diseases, an early diagnosis is crucial for life-saving treatments and preventing life-long disabilities. 

To address the fourth priority, National Institute for Health and Care Excellence (NICE) reassessed its approach for technology evaluations that determine if a treatment is cost-effective to be offered by the NHS. Guidance was published highlighting the changes, one of which was the consideration and acceptance of a wider range of evidence including RWE⁽⁶⁾. This offers great flexibility as data from clinical trials for rare diseases that is often limited by very small patient numbers may be supplemented by RWE from affected patients. In addition, in June 2022, the Innovative Medicines Fund was launched which will allow easier and quicker access to life-saving and ground-breaking therapies for patients, without having to wait for prior approval by the NICE as an NHS funded therapy. Data from real-world sources will be used as part of the NICE assessment of cost-effectiveness⁽⁷⁾.

Nonetheless, the generation of RWE for rare disease comes with great challenges. One inherent challenge with all rare diseases is the low number of patients per disease. This not only means low availability of medical evidence, but also restricted access to data. Moreover, patients are usually treated across primary, secondary and tertiary care settings leading to information silos and the need to combine data from multiple sources that may not be compatible.  As most rare diseases have a genetic link, data sources will need to combine both clinical and genetic information. Finally, these diseases are often complex with expertise in pathophysiology, natural history, clinical manifestations, and treatment pathway being limited to very few specialists. To successfully, conduct an RWE study for rare diseases, not only will specialised data-sources be required but also a multidisciplinary team of epidemiologists, medics, geneticists, and statisticians are needed.

IQVIA has a longstanding heritage of conducting RWE studies using a variety of evidence platforms, including Genomics England (GEL), one of the world’s largest whole genome cohorts for rare diseases that is linked longitudinal clinical data. Some excellent examples of studies that can generate RWE for rare disease using GEL include comparison of natural history of disease to understand rate of progression of disease based on genetic markers and clinical endpoints, identification of prevalence/incidence of specific mutation within cohort and identification of novel genomic biomarkers that correlate with the disease severity/progression. IQVIA has a dedicated bioinformatics team with extensive experience working with genomics data in GEL to support such RWE studies.

Other databases that IQVIA can leverage to generate powerful insight into rare disease patient journey from primary to secondary care and to understand unmet need and healthcare resource utilisation, are Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). Information from CPRD provides Longitudinal Electronic Healthcare Record data of patients collected from GP practices while HES provides details of all admissions, A&E attendances and outpatient appointments at NHS hospitals across England.

For more novel and niche approaches that cannot be met using information from databases, we are able to approach sites in IQVIA’s Prime Site Network of leading research and academic healthcare organisations to deliver Primary Data Collection studies (PDCs). Here, data is collected directly from electronic health records, patients or healthcare professionals via interviews and patient/clinician reported outcomes measures to create an enriched and tailored database suitable for purpose.

Finally, as the patient voice in rare disease space can provide insight that cannot be achieved from any data platform, IQVIA has dedicated teams to incorporate patient input in various ways.  The EMEA Patient Advocacy team can engage and harness expertise of rare disease PAGs to enable direct input from patients through PAG owned communities, registries, and communications channels. In addition, IQVIA’s dedicated Patient Centered Solutions team can help design patient experience studies, supporting with collection and interpretation of various types of patient experience data. To provide a 360⁰ rare disease solution, the expertise of the Rare Disease Centre of Excellence, which is comprised of a group of physicians and scientists, can be leveraged.

IQVIA is committed to contributing to the advancement of rare disease landscape to facilitate better diagnosis and treatment options for patients who have long been neglected. As highlighted in this blog, IQVIA can use its unparalleled data and scientific expertise alongside advanced bioinformatics to provide any rare disease stakeholder with novel and tailored RWE solution fit for purpose.

To understand how IQVIA’s team of RWE experts can support you to leverage these powerful RWD sources, contact us here: RWI_RFP-and-queries@iqvia.com.

References:

1. Nguengang Wakap S, Lambert DM, Olry A, Rodwell C, Gueydan C, Lanneau V, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020 Feb;28(2):165–73.
2. England Rare Diseases Action Plan 2022 [Internet]. GOV.UK. [cited 2023 Jan 12]. Available from: https://www.gov.uk/government/publications/england-rare-diseases-action-plan-2022/england-rare-diseases-action-plan-2022
3. Innovative Funding Models for Treatment of Rare Diseases [Internet]. [cited 2023 Jan 12]. Available from: https://www.iqvia.com/locations/asia-pacific/library/white-papers/innovative-funding-models-for-treatment-of-rare-diseases
4. Endocrinology TLD&. Spotlight on rare diseases. Lancet Diabetes Endocrinol. 2019 Feb 1;7(2):75.
5. The UK Rare Diseases Framework [Internet]. GOV.UK. [cited 2023 Jan 12]. Available from: https://www.gov.uk/government/publications/uk-rare-diseases-framework/the-uk-rare-diseases-framework
6. Changes we’re making to health technology evaluation | Technology appraisal guidance | NICE guidance | Our programmes | What we do | About [Internet]. NICE. NICE; [cited 2023 Jan 22]. Available from: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-technology-appraisal-guidance/changes-to-health-technology-evaluation
7. NHS England » Innovative Medicines Fund [Internet]. [cited 2023 Jan 22]. Available from: https://www.england.nhs.uk/medicines-2/innovative-medicines-fund/#when-will-funding-through-the-innovative-medicines-fund-be-available-for-medicines-recommended-for-managed-access