Saturday, 4 December, 2021

Basics Of Clinical Trial

Prof. Dr. Shyam P Lohani


Recently, there have been continuous debates on the clinical trial of a vaccine in Nepal. It seems most of the issues associated with the debate have been revolving on whether clinical trial should be allowed in developing countries or not. Isn’t it an exploitation of people from resource poor settings in such a study? Before we get involved ourselves in the debates, it is important to know about the basics of clinical trial and its boundaries. The development of new methods, devices, drugs or vaccines requires extensive testing on animals, human cell cultures and human beings. A product, a drug or vaccine or device or a method, should undergo different stages of tests and trial before it is allowed to be marketed. Therefore, clinical trial is essential for the development of medical science and clinical care of patients. Before doing clinical trials, researchers perform preclinical study in human cell cultures or animal models. If the preclinical study is promising, then researcher consider for further clinical trials to evaluate how well it works in human.

Clinical trials are conducted in different phases during which several specific questions are asked. Each of the subsequent phases is based on the result of previous phase. Phase 0 clinical trial is done with a very few number of human participants usually less than 15. The investigator evaluate either small dose of medication has different effect than in preclinical study and also evaluate the toxicity. This phase is done to seek answer about the safety of the product. The phase I clinical trial is conducted among healthy human volunteers usually 20-80 people.
This phase will determine the maximum dose a human can tolerate without a serious side effect. During this phase, researcher closely monitors the effects of medication on the human body. In addition to the safety and ideal dose of a drug, the ideal route of administration is also determined in this phase. Phase II clinical trial involves few hundreds participants who are living with the disease condition for which new drug is meant to treat. `During this phase, researcher monitors participants over several months or years to see how effective the medicine is and also evaluates any side effects it might cause.
Phase III clinical trial involves up to 3000 participants having condition for which new drug is meant to treat. This phase compares the effectiveness of new medication over existing treatment for the same condition. This phase runs over several years and to qualify for marketing, it has to show evidences that the new medication is at least as effective as existing one. The randomisation is necessary for the comparison purpose; therefore, randomisation is the essence of phase III clinical trial.
Phase III clinical trials are usually double-blinded which means both the participants and investigators do not know which medication are participants are taking. Owing to large number of participants and longer duration of study, rare and long-term side effects are observed. After successful completion of phase III trial, a new medication is allowed to enter market. It requires several years and huge amount of money for the successful completion of preclinical studies and phases of clinical trial before a product such as drugs, vaccines or medical devices are allowed to enter in to the market.
The clinical trials in vulnerable populations such as children, pregnant women, uniformed forces, psychiatric patients and elderly are especially complex and challenging. The most of the controversies about the clinical trials revolve around exploitation of the trial participants. Unlike other emerging countries, Nepal does not make it obligatory to have clinical trials conducted on their population before marketing approval is granted for new drug, vaccine or medical device.
It is important to have a national policy to make trial sponsor responsible before a trial begins to have plan and provisions of making vaccines continuously available to the all participants or all population of the host country even after the trial completes with positive outcome at the affordable costs. Clinical trials aims to assess the efficacy of the drug or vaccine or a device, it also carries inherent safety risk due to possible adverse effects associated with experimental product. The risks involved must be communicated to the participants and if the participants are people from vulnerable groups, then to their care givers. The outcome and implications of the clinical trial is another concern as there is no guarantee that the trial results new and effective alternative for the disease. In many instances, clinical trials fail to provide evidences of safety and efficacy and the process of drug development stops.

It is equally important to evaluate either the clinical trial is addressing local and/or country’s health priority. If the disease or condition is mainly prevalent in resource poor settings, then clinical trial may be justified in low and middle-income countries. Many of the trial participants in developing countries due to different socio-cultural disadvantages such as poverty, illiteracy, and limited health care availability may think that the experimental drug may be the opportunity to get good and proper clinical care without fully knowing the risks associated with trial product. The Nepal Health Research Council has national guidelines for clinical trials since 2005 and it is recommended that to revisit the document to update as per the recent development on health research ethics.

(Prof. Lohani is the Founder and Academic Director of Nobel College. He can be reached at