Impact and evolution of a philanthropic global network providing clinical genomic testing
Clinical Genetics and Therapeutics
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Primary Categories:
- Health Care Inequities and health disparities
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Secondary Categories:
- Health Care Inequities and health disparities
Introduction:
Rare genetic diseases (RGD) impact at least 250 million individuals worldwide, the majority of whom reside in low- and middle-income countries (LMIC) and experience prolonged diagnostic odysseys due to barriers accessing specialist clinicians and molecular testing. The iHope program is a philanthropic program that provides no-cost clinical genomic testing to underserved children with suspected RGD. Here we report on an updated assessment of the diagnostic yield and the impact of test results on change of management (COM) in more than 2,000 individuals supported by the program, and its evolution to a globally distributed network of clinical genomic laboratories.
Methods:
We have previously described a total of 1,164 individuals supported by the iHope program, drawn from 25 clinics in eight countries. Here we present an additional 842 individuals who were provided with clinical genome sequencing (cGS) through iHope by Illumina Laboratory Services, from June 2016 through January 2024, resulting in a total cohort of 2,006 individuals with suspected RGD. Clinicians were asked to complete a clinical impact survey to assess the influence of genomic test results on COM.
Results:
Forty-seven percent of individuals (939/2006) were referred from one of ten sites in LMIC in Peru (3), Mexico (2), Croatia (1), Democratic Republic of the Congo (1), Ghana (1), North Macedonia (1) or Zimbabwe (1). Across the aggregate cohort the diagnostic yield was 40.3% (816/2006), with individuals from LMIC more likely to receive a diagnosis (50.9%, 478/939) compared to individuals from HIC (31.1%, 338/1067). Clinician-completed surveys to assess COM were available for a total of 1,239 individuals (674 HIC, 565 LMIC). COM was 50% overall (625/1239), including referrals, imaging, testing, therapeutics and palliation. COM was higher for individuals from LMIC sites (69.6%, 393/565) compared to individuals from HIC sites (34.3%, 231/674). To control for the elevated diagnostic yield at LMIC sites, analyses were stratified by positive test outcome. Individuals with a positive test result from LMIC sites were, unexpectedly, more likely to experience COM compared to individuals from HIC sites (LMIC 75.2% [240/319] vs HIC 60.7% [142/234], OR 1.97, 95% CI 1.37-2.84, 0.0004). Overall, test results impacted genetic counseling topics in 56.5% (700/1239).
These findings have supported the development of a distributed network of iHope testing laboratories and partner clinical sites. Participating laboratories receive subsidized materials to provide no-cost cGS or exome sequencing to patients. In 2024, twenty-nine laboratories applied to become iHope partners. Laboratories were assessed using a pre-defined rubric that included accreditation status, test definition (including the number and type of variants assessed), interpretation and reporting practices, testing volume and quality systems. The awardees were SickKids and Children's Hospital of Eastern Ontario in Canada, the New York Genome Center in the United States and Mendelics in Brazil. Concurrently, a network of 15 clinical sites, all of which were previous iHope program partners, was established across eight countries. This genomic services model is tractable and scalable and will support thousands of patients per year.
Conclusion:
Data from the first 2,006 iHope program participants indicates that the program model is robust, with durable, reproducible impacts over time. This supported the extension of the program model from a centralized testing laboratory to a distributed laboratory network. The model is technology-agnostic and can support multiple testing platforms and modalities. Over the next five years, iHope aims to scale to include 10 laboratories and 50 clinical sites, with a focus on growth in LMIC and enablement of in-region or in-country testing.
Rare genetic diseases (RGD) impact at least 250 million individuals worldwide, the majority of whom reside in low- and middle-income countries (LMIC) and experience prolonged diagnostic odysseys due to barriers accessing specialist clinicians and molecular testing. The iHope program is a philanthropic program that provides no-cost clinical genomic testing to underserved children with suspected RGD. Here we report on an updated assessment of the diagnostic yield and the impact of test results on change of management (COM) in more than 2,000 individuals supported by the program, and its evolution to a globally distributed network of clinical genomic laboratories.
Methods:
We have previously described a total of 1,164 individuals supported by the iHope program, drawn from 25 clinics in eight countries. Here we present an additional 842 individuals who were provided with clinical genome sequencing (cGS) through iHope by Illumina Laboratory Services, from June 2016 through January 2024, resulting in a total cohort of 2,006 individuals with suspected RGD. Clinicians were asked to complete a clinical impact survey to assess the influence of genomic test results on COM.
Results:
Forty-seven percent of individuals (939/2006) were referred from one of ten sites in LMIC in Peru (3), Mexico (2), Croatia (1), Democratic Republic of the Congo (1), Ghana (1), North Macedonia (1) or Zimbabwe (1). Across the aggregate cohort the diagnostic yield was 40.3% (816/2006), with individuals from LMIC more likely to receive a diagnosis (50.9%, 478/939) compared to individuals from HIC (31.1%, 338/1067). Clinician-completed surveys to assess COM were available for a total of 1,239 individuals (674 HIC, 565 LMIC). COM was 50% overall (625/1239), including referrals, imaging, testing, therapeutics and palliation. COM was higher for individuals from LMIC sites (69.6%, 393/565) compared to individuals from HIC sites (34.3%, 231/674). To control for the elevated diagnostic yield at LMIC sites, analyses were stratified by positive test outcome. Individuals with a positive test result from LMIC sites were, unexpectedly, more likely to experience COM compared to individuals from HIC sites (LMIC 75.2% [240/319] vs HIC 60.7% [142/234], OR 1.97, 95% CI 1.37-2.84, 0.0004). Overall, test results impacted genetic counseling topics in 56.5% (700/1239).
These findings have supported the development of a distributed network of iHope testing laboratories and partner clinical sites. Participating laboratories receive subsidized materials to provide no-cost cGS or exome sequencing to patients. In 2024, twenty-nine laboratories applied to become iHope partners. Laboratories were assessed using a pre-defined rubric that included accreditation status, test definition (including the number and type of variants assessed), interpretation and reporting practices, testing volume and quality systems. The awardees were SickKids and Children's Hospital of Eastern Ontario in Canada, the New York Genome Center in the United States and Mendelics in Brazil. Concurrently, a network of 15 clinical sites, all of which were previous iHope program partners, was established across eight countries. This genomic services model is tractable and scalable and will support thousands of patients per year.
Conclusion:
Data from the first 2,006 iHope program participants indicates that the program model is robust, with durable, reproducible impacts over time. This supported the extension of the program model from a centralized testing laboratory to a distributed laboratory network. The model is technology-agnostic and can support multiple testing platforms and modalities. Over the next five years, iHope aims to scale to include 10 laboratories and 50 clinical sites, with a focus on growth in LMIC and enablement of in-region or in-country testing.