Deepti Dubey, PhD and Harsha K Rajasimha, PhD- IndoUSrare.
The biopharmaceutical industry relentlessly strives to develop life-saving drugs, offering hope to countless patients globally. Clinical trials stand as the bedrock of medical research, shaping innovative treatments. Ironically, nearly nine out of ten drug candidates fail through the “valley of death” (i.e., during phases I, II, and III of clinical trials and regulatory review process).1 This leads to immense suffering for patients and increases the research and development costs to the biopharmaceutical sponsors.
A critical factor in these failures is inadequate patient participation, including from underrepresented groups. Approximately 12% of trials on clinicaltrials.gov terminate, with insufficient enrollment as the primary cause.2 A recent analysis shows that a low accrual rate has been the most common termination reason from 2010 to 2021, comprising 25.4% of all terminated trials.3 Therefore, ensuring adequate patient enrollment and retention emerges as a pivotal challenge in clinical trial success.
Including racially and ethnically diverse participants in a clinical trial ensures a more accurate evaluation, reducing disparities and promoting equitable healthcare access. This approach is crucial for certifying that approved medicines are safe and effective for the broader patient population they serve, fostering trust, and advancing biomedical knowledge.4 However, the persistent lack of diversity in clinical trials remains an enduring issue, now being actively addressed by both regulatory bodies5 and pharmaceutical companies like Pfizer6 and other member companies of The Pharmaceutical Research and Manufacturers of America (PhRMA).7
Existing literature highlights significant racial disparities in clinical trial participation. For instance, the representation of Asians, encompassing individuals from the Far East, Southeast Asia, and the Indian subcontinent, in trials conducted from 2000-2020, remained consistently low at approximately 1%.8 Notably, the Indian subcontinent alone comprises a quarter of the global population, with over 4.2 million individuals of Indian descent residing in the United States, underscoring the potential impact of increased representation in clinical research."
Active participation of Indians in clinical trials is crucial for the global success of such endeavors. This is especially vital in the context of rare disease trials, which already have a low number of patients as a major hurdle in study designs. The inclusion of patients from the Indian subcontinent is of paramount importance in these trials, given India's notable burden of rare diseases attributed to factors such as a high birth rate, elevated consanguinity rates, and various socio-economic considerations.
Root Causes of the Underrepresentation of the Indian Subcontinent in Clinical Trials
Limited Awareness and Access to information
A significant challenge in recruiting participants from the Indian subcontinent arises from a lack of awareness and access to information regarding rare diseases and clinical trials. Many individuals in these regions may not be familiar with the concept of clinical research or may hold misconceptions about its purpose and potential benefits. These misconceptions are often exacerbated by language barriers.
Stakeholders play an indispensable role in raising awareness and enhancing access to information about rare disease clinical trials. Through their collective efforts, they help bridge gaps in knowledge, ensuring that patients, healthcare providers, and the broader community possess the information necessary to participate effectively. Possessing access to patients and their trust, patient advocacy groups stand at the forefront of raising awareness. Indo US Organization for Rare Diseases (IndoUSrare.org), a non-profit global patient advocacy organization, provides tech-enabled patient concierge to connect rare disease patients in India, the US, and globally with clinical trials, patient advocacy groups, research initiatives, and international consortia. This invaluable network includes esteemed organizations and resources such as the National Institutes of Health GARD service, ClinicalTrials.gov, the clinical trials registry of India, Global Genes, the International Rare Diseases Research Consortium (IRDiRC), National Organization for Rare Disorders (NORD), RARE-X, Rare Disease International (RDI), Undiagnosed Diseases Network International (UDNI), and a growing network of medical genetics experts across India (Research Corps) that IndoUSrare has been building over the years. This provides valuable support and updated resources to educate patients and their caregivers.
Socioeconomic Disparities
The Indian subcontinent encompasses a wide range of economic disparities, with a significant portion of the population facing financial constraints. This can deter individuals from considering getting the needed treatment or participation in clinical trials, especially if they perceive it as financially burdensome. Additionally, there are social and cultural taboos associated with rare diseases that result in social isolation of the patient creating barriers to their awareness and participation in clinical trials.
Language is a huge barrier when it comes to engaging the rural Indian population. IndoUSrare received the #RAREis Global Advocacy grant from Horizon Therapeutics this year to translate education and awareness content in some of the most common local Indian languages.
There are various options for financial assistance for the treatment of rare diseases that could be available to these patients through government grants, crowdfunding, and private or non-profit organizations such as the Patient Advocate Foundation (PAF) and The Assistance Fund (TAF). However, these assistance programs are not well advertised and have a complex application process. One of the projects at IndoUSrare is assessing the awareness and accessibility of financial support schemes within the rare disease communities in India. Through surveys targeting participants such as patients and healthcare professionals, we aim to gather valuable insights. The results obtained from these initiatives have been published and utilized towards increasing awareness about financial assistance programs available for families battling rare diseases. This availability of financial support instills hope and confidence in patient families, empowering them to explore treatment options and potentially participate in relevant clinical trials.
Limited Access to Healthcare and Clinical Trial Sites
Inequities in access to healthcare services, especially in rural areas, and the concentration of clinical trial sites in urban medical centers present logistical challenges.
The ongoing digitalization initiative in India, coupled with advancements in healthcare technology, holds the potential to revolutionize healthcare accessibility in this vast and diverse nation. It is projected that nearly 60% of India's population will have internet access by the close of 2023. This presents a significant opportunity for leveraging telemedicine, mobile health apps for data collection, e-pharmacies, electronic health records, on-site healthcare services, and remote monitoring devices. These innovations can facilitate decentralized clinical trials within the Indian population. In recent years, there has been a growing recognition of the need for participant-centric approaches, particularly for segments such as children, individuals with physical or cognitive impairments, and those requiring chronic treatment - all of which are prevalent in rare diseases.9
Inadequate Representation in Research Leadership
A lack of representation from the Indian subcontinent in clinical research leadership perpetuates the underrepresentation issue.
IndoUSrare was founded to address the unmet needs of rare disease patients living in the Indian subcontinent which represents almost 25% of the world population by fostering collaborations with organizations and agencies in the United States (the single largest nation funding rare disease research).
Lack of Relevant Patient Data for Rare Diseases
Conducting clinical trials in a population is significantly hindered by the absence of pertinent epidemiological data. This challenge is particularly pronounced in the case of rare diseases, which face multiple barriers including low disease prevalence, limited awareness, resource constraints, diagnostic complexities, societal stigma and isolation, limited research expertise, and the absence of centralized rare disease registries. These registries play a crucial role in identifying and enrolling patients in clinical trials.
IndoUSrare partnered with RARE-X and Global Genes in 2021 to better understand India's rare disease landscape and completed a feasibility study to identify and overcome barriers to establishing patient-owned health data registries for seamless national and international data sharing. The results of this study are published and can be accessed on the indousrare.org portal. Furthermore, IndoUSrare is undertaking scientific studies to estimate the prevalence and incidence of specific rare diseases in India, contributing to the advancement of research in rare disease epidemiology.
By addressing these root causes and implementing strategic initiatives, global patient advocacy organizations can enhance cross-border collaborations and knowledge sharing. These steps are key to enhancing patient participation and diversity in clinical trials, ultimately advancing research and treatment options for rare disease patients in the Indian subcontinent. To learn more, join this conversation at the Indo US Bridging RARE Summit scheduled for Oct 29, 30, 2023 at George Mason University campus in Arlington, VA; https://bridgingrare.org.
References
- Why 90% of clinical drug development fail and how to improve it? Acta Pharm Sin B. 2022 Jul;12(7):3049-3062.
- Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination. PLoS One. 2015 May 26;10(5):e0127242
- Trial termination analysis unveils a silver lining for patient recruitment. Clinical Trials Arena, October 2022.
- Why Diverse Clinical Trial Participation Matters. N Engl J Med. 2023 Apr 6;388(14):1252- 1254.
- FDA Takes Important Steps to Increase Racial and Ethnic Diversity in Clinical Trials. FDA Press release, April 2022.
- Ensuring Diversity in Clinical Trials to develop breakthroughs for All. Pfizer report, 2022.
- Industry-Wide Principles To Enhance Diversity In Clinical Trial Participation. The Pharmaceutical Research and Manufacturers of America (PhRMA), October 2020.
- Race/ethnicity reporting and representation in US clinical trials: A cohort study. Lancet Reg Health Am. 2022 Jul;11:100252
- Decentralized clinical trials and rare diseases: a Drug Information Association Innovative Design Scientific Working Group (DIA-IDSWG) perspective. Orphanet J Rare Dis. 2023 Apr 11;18(1):79.
Deepti Dubey, Ph.D., is an accomplished researcher with expertise in Molecular Genetics, Neurological Disorders, and Rare Diseases from esteemed institutions. In collaboration with non-profit patient organizations, she has driven research initiatives for accelerating breakthroughs for rare diseases. With a Clinical Trials Specialization, Deepti is a scientific writer at IndoUSrare.
Harsha K Rajasimha, Ph.D., is the Founder and Executive Chairman of the Indo US Organization for Rare Diseases (IndoUSrare) with the mission to make rare disease research and clinical trials universally accessible. Harsha will be chairing the Indo US bridging RARE Summit (https://bridgingrare.org) on Oct 29 & 30, 2023, at the George Mason University campus in Arlington, VA. To learn more, visit https://indousrare.org.
Publication Details
This article appeared in Pharmaceutical Outsourcing:
Vol. 4, No. 24
Oct/Nov/Dec 2023
Pages: 18-20
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