All you need to know about: clinical trials

 All you need to know about: clinical trials 

A clinical trial is an organised method of determining whether one approach to treatment is better than another: it begins with a question and ends with a verdict— the outcome being effectiveness or failure

Randomising participants to different groups—one receiving the experimental drug and another a placebo—reduced bias and improved inference quality. Photograph used for representational purposes only | Photo Credit: Getty Images/iStockphoto

A sailor’s experiment

In 1747, Scottish naval surgeon James Lind conducted what is now considered the world’s first controlled clinical trial aboard HMS Salisbury. Scurvy, a deadly disease causing bleeding gums and fatigue, was devastating for sailors. Unaware of vitamins, at that stage, Lind divided 12 affected sailors into six pairs, each receiving a different treatment. Only those given oranges and lemons recovered. Though vitamin C wouldn’t be identified for another century, Lind’s use of comparison and observation led to a medical breakthrough. His experiment laid the foundation for modern clinical trials—structured studies on humans to assess the safety and effectiveness of treatments, vaccines, or preventive interventions.

What is a trial?

A clinical trial begins with a question and ends with a verdict— the outcome is effectiveness or failure. A clinical trial is an organised method of determining whether one approach to treatment is better than another. These trials evolved greatly during the 20th century. In 1948, British epidemiologist Sir Austin Bradford Hill introduced the randomised controlled trial, testing the efficacy of streptomycin in pulmonary tuberculosis. Randomising participants to different groups—one receiving the experimental drug and another a placebo—reduced bias and improved inference quality. Randomisation, blinding, and controlled comparisons became the cornerstones of modern clinical research.

Types and phases of clinical trials

Clinical trials vary in design based on the research question. In a parallel trial, different groups receive different treatments throughout. In a crossover trial, each participant receives both treatments in sequence. Other designs include factorial trials, testing multiple interventions simultaneously, and cluster trials, randomising groups rather than individuals. Blinding and placebos help reduce bias and isolate true treatment effects. Before human testing, new drugs undergo preclinical studies in labs and animals. Phase 1 assesses safety in healthy volunteers through microdosing. Phase 2 evaluates early effectiveness in patients. Phase 3 compares with standard care in large, multi-centre trials. Phase 4, after approval, monitors long-term safety in real-world settings. These phases ensure scientific rigour and public safety at every step.

Yet, for all the rigour in conducting these studies, a problem persisted: selective reporting. Often, only favourable results found their way into journals, while unfavourable or inconclusive trials were quietly buried. This distorted the evidence landscape, misled clinicians, and led to wastage of resources due to the repetition of unsuccessful and unpublished trials.

To improve, the concept of clinical trial, registries was born. These registries act as public ledgers, documenting the intention to conduct a trial and the protocol, methods, and outcomes regardless of whether the study sees the light of publication.

Inside a registry

A clinical trial registry includes a wide range of information: the trial title, sponsor and funding details, scientific rationale, ethical approvals, inclusion and exclusion criteria, intervention and comparator arms, primary and secondary outcomes, recruitment status, expected start and end dates, and updates on results or termination. The most well-known global registry, ClinicalTrials.gov, was launched in 2000 by the U.S. National Library of Medicine. The broader movement for international harmonisation began with the World Health Organization’s International Clinical Trials Registry Platform (ICTRP), established in 2006, which linked multiple national registries across the globe. The WHO’s International Clinical Trials Registry Platform is not for direct registration; researchers must register through one of 17 recognised primary registries globally. The goal was simple: anywhere in the world, any human clinical trial should be prospectively registered in a public database accessible to all for knowledge sharing and participation in trials.

Rise of regulation

Over the years, clinical trial registration became more than a best practice—it became mandatory. The International Committee of Medical Journal Editors (ICMJE) announced that no member journal would publish results of trials that weren’t registered before patient enrolment. WHO formulated minimum dataset requirements for trial registries and called upon governments and institutions to make trial registration a legal obligation. Countries such as India responded swiftly. The Clinical Trials Registry – India (CTRI) was launched in July 2007 by the National Institute of Medical Statistics under the Indian Council of Medical Research. By 2009, it became mandatory to register all interventional trials conducted in India prospectively. Registering a trial in CTRI requires the investigator to create an account, fill out the structured trial registration data set online, attach relevant ethics committee approvals, and submit for verification. CTRI administrators review information, and a unique registration number is issued once it is accepted.

WHO’s 2025 update

Despite these strides, gaps remained. A significant number of trials, even after registration, failed to report their results publicly. In April 2025, WHO released a long-awaited guidance document to plug this gap. The new guideline mandates that within 12 months of trial completion, summary results must be made available in the registry. The guidance identifies eight minimum elements to be reported: the final trial protocol and statistical analysis plan (including amendments), the completion status and whether the trial ended early, dates of reporting both in the registry and journals, participant flow across arms, baseline participant characteristics, detailed outcome results (including subgroup analyses and comparisons), harms or adverse events, and declarations of conflict of interest by the investigators.

This new technical advisory draws inspiration from the CONSORT 2025 reporting standards used in academic publishing, bringing consistency between what is published in journals and what is recorded in registries. It also encourages using structured fields for reporting, which improves searchability, aggregation, and monitoring of global health research. WHO’s platform is now working towards integrating these updates into a combined ‘Registration and Results Data Set.’

This change reflects a profound ethical principle: every trial must contribute to scientific knowledge, even if the result is inconclusive, unfavourable, or abandoned midway. Trials are no longer seen as closed academic exercises but as public goods. A failed trial, transparently reported, is as valuable as a successful one—it prevents duplication, protects patients, and refines research. Like silent archivists, registries ensure every data point finds a place in history and that every participant’s contribution is fully acknowledged. The registry is a quiet custodian of truth in a world grappling with medical misinformation and hurried innovations.

(Dr. C. Aravinda is an academic and public health physician. The views expressed are personal. aravindaaiimsjr10@hotmail.com)