The clinical trial landscape has undergone significant changes since the concept of trials was first introduced, with notable shifts in the social, ethical, and regulatory environments worldwide.
The Clinical Trial Landscape Is Evolving
Today, there is a broader understanding of the substantial health, social, and economic benefits that research investment brings. Clinical trials and the development of interventions are now supported not only by industry but also non-industry organisations like academic institutions, government agencies, and public–private partnerships, sometimes with the help of external partners in translational research.
Ethical principles have been updated, particularly through the Declaration of Helsinki, and the development of clinical trial guidance, such as the CIOMS International Ethical Guidelines. Additionally, ICH guidelines – specifically ICH E8(R1) and ICH E6(R3) – are now available, alongside recent guidance from the Good Clinical Trials Collaborative and new or updated pathways from regulators.
There has been growing interest in trial methodology, with an increasing focus on flexible and practical trial designs. There is a growing appreciation for how routinely collected data, also referred to as real-world data, can enhance the value and efficiency of clinical trials. For example, data on patient health or healthcare delivery – collected from sources like electronic health records, medical claims, disease registries, or digital health technologies – can support trial enrolment and outcome assessments.
In recent years, patient organisations and advocacy groups have played an increasingly important role, championing the involvement of patients, communities, and the public in clinical trials as a key component of their design and execution. However, more efforts are needed to ensure meaningful engagement with these groups throughout trial development and implementation.
Persistent Challenges in Clinical Trials
Despite the recognised importance of clinical trials, there is an urgent need to reduce inefficiencies and scale trials to generate reliable evidence at reasonable costs. In many areas of health, the evidence base remains inadequate, with decision-making often hampered by a lack of well-designed and well-conducted trials. This issue affects countries across all income levels – high, middle, and low.
As a result, effective and safe interventions may be overlooked, or ineffective and harmful interventions may continue to be used. For instance, millions of doses of ineffective treatments were administered during the COVID-19 pandemic.
Several factors contribute to this waste in clinical trials: trials that are never initiated or completed, unclear research questions, duplication of existing research, inefficient trial processes, or results that are never published. Poorly designed or incomplete trials lead to a significant loss of resources, which could otherwise be used for better-designed studies. Moreover, a risk-averse mindset often stifles innovation and leads to unnecessarily burdensome trial procedures.
Another key challenge is the lack of efficient and coordinated procedures for approving clinical trials, which is exacerbated by wide variability in regulatory and ethical approval processes between countries and regions. While some countries have mature systems, inefficiencies and overly risk-averse approaches can still slow progress. Lengthy approval timelines can diminish enthusiasm and hinder recruitment, especially in local populations, reducing the evidence base for those trials aim to help.
Many countries lack the necessary resources for a robust clinical trial infrastructure or have yet to achieve adequate efficiency. The variety of applications and lengthy timelines delay initiation, potentially deterring engagement in clinical research. This problem is particularly pronounced in multiregional or international trials, which are crucial for ensuring statistical power and broad representativeness. Additionally, intermittent funding for clinical trials often leads to periodic fallow or “cold” periods where infrastructure is underutilised, resulting in inefficiencies, skill loss and neglect of key areas within the clinical trial ecosystem.
The New WHO Guidance for Best Practice in Clinical Trials
This newly released guidance responds to the World Health Assembly’s request, outlined in resolution WHA75.8 (2022), for the Director-General to strengthen clinical trials by ensuring high-quality evidence for health interventions. It aims to improve research quality and coordination by identifying best practices and proposing measures to reinforce the global clinical trial ecosystem. The guidance includes the review of existing protocols and developing new recommendations as needed on best practices for clinical trials.
Building on the World Health Organisation’s earlier work on research capacity, this updated guidance is tailored to the current context of well-designed and effectively implemented clinical trials, as outlined in WHA75.8 (2022). It seeks to enhance research efficiency, reduce waste, and ensure clinical trials remain operational and responsive, both for endemic conditions and in times of emergencies or pandemics.
From Guidance for best practices for clinical trials. Geneva: World Health Organization; 2024. Licence: CC BY-NC-SA 3.0 IGO.
Veronique Ropion, MD
Strategic Projects Director, Pharmalys Ltd
