Clinical Trials in Resource-Limited Settings: Exploring Nepal's Challenges and Solutions

A Cochrane review of rotavirus vaccines revealed 80–90% protection against severe gastroenteritis in high-resource settings compared to 40–60% efficacy in low-resource settings. Why do interventions that work in industrialized countries face challenges in demonstrating effectiveness in developing nations?

Well, the simple answer lies in the healthcare infrastructure disparities, socio-economic differences, unique disease dynamics, and cultural diversity that collectively shape the effectiveness of interventions between the countries.

With a history of only about 22 years, Nepal is relatively new to clinical trials. The first clinical trial in Nepal , conducted in July 2001 by the U.S. Army and GlaxoSmithKline, assessed the hepatitis E vaccine’s safety and efficacy. After the COVID-19 upsurge, diverse trials, including drugs, vaccines, and Ayurvedic formulations, actively involve the local population for improved healthcare outcomes.

Challenges to conduct clinical trials in Nepal-

Nepal being a low income country, struggles with the aftermath of insignificant yearly budget allocation towards the health sector. Only 4.95% of the total budget for the fiscal year 2023/24 AD in the country is allocated to Sustainable Development Goal No. 3 - Good Health and Wellbeing. In the 2020/21 fiscal year, 0.2% of the total health budget, amounting to 199 million rupees, was allocated to the federal government for health-related research in the country. By this data, we could clearly analyze, limited research funding to be one of the major challenges to conduct clinical trials in the country.

 Cutting edge technologies required for the clinical trials in Nepal have to be brought from abroad, posing logistical challenges. Sponsors face flight delays varied from 1 to 8 hours depending upon weather and infrastructure issues, which hinders the entire trial calendar. Limitations of the basic and necessary resources for trial conduction, discourages the international Sponsors, Contract Research Organizations (CROs), INGOs and related stakeholders to invest in conducting clinical trials in Nepal.

 Regulatory challenges include inconsistent or unclear regulatory frameworks, capacity building for regulatory professionals, and addressing delays in the approval process. A study highlights that, the typhoid conjugate vaccine Vi-DT should have completed phase III trial in 2020, but regulatory approval and licensure from NHRC and DDA was obtained only in 2021.

Fear, distrust, and possible preconceived notions about clinical trials or suspicions of ‘research’ exists highly in the Nepalese community. Most recent example is the vaccine hesitancy seen during COVID-19 pandemic.38.9% participants in a study conducted in Nepal showed initial vaccine hesitancy due to the aforementioned reasons. This directly affects the patient recruitment and retention process during the trials.

Solutions to overcome the problems:

 Governments in the resource limit settings should focus to encourage public-private partnerships (PPPs) and international collaborations to fund the clinical trials. They can also offer tax incentives to stimulate private investment in research, invest in research infrastructure, and optimize regulatory processes to reduce trial costs. Having a good share of budget allocation for clinical trials in the Red Book is a plus point.

Overcoming logistical barriers in clinical trials involves strategic planning. Implementing effective strategies such as leveraging technology, optimizing supply chain management, and enhancing transportation and communication infrastructure are crucial.

 Flexibility in trial protocols, adherence to ethical standards, and robust post-trial access plans help navigate regulatory complexities. Collaboration between researchers and regulators is essential to address evolving frameworks and potential delays.

 To address the shortage of skilled healthcare professionals and researchers, it is imperative to invest in training programs that enhance their capabilities. This involves designing tailored courses focusing on clinical research methodologies, ethical considerations, and regulatory compliance, collaborating with national and international entities.

Conducting culturally sensitive education campaigns to dispel myths and misconceptions, emphasizing the benefits of clinical trials, and highlighting successful stories can help alleviate fears. Building trust through education, open communication, and community involvement is essential to overcome skepticism and encourage participation in clinical trials in the Nepalese community.

The Global Forum for Health Research report underscores that bolstering research capacity in developing countries is a highly effective and sustainable strategy for promoting health and development, addressing gaps in health research, and contributing to global health outcomes. By addressing these challenges and implementing tailored solutions, it is possible to enhance the feasibility and success of clinical trials in resource-limited settings like Nepal.