All human beings around the world are fighting the Covid pandemic; this now seems to be killing millions of humans day by day. Just as the spread of the virus has disrupted all kinds of work around the world, so too is the deathly cry for the future of human healthcare. In order to defeat Covid and save lives, various medicines and vaccines were developed all over the world. Western medicine and even traditional medicine studies have teamed to develop and experiment with various chemical formulations to control the spread of the virus. There has been a lot of information reporting on the drugs that have been developed so far to control the spread of Covid-19, mainly through the mainstream media and social media. (i.e. Vaccines developed to fight against Covid-19 such as Aztraseneca, Sputnik V, Sinopharm and Covax, etc.). At the same time, the media began to focus more on the production of drugs, the clinical trials involved, and the processes involved as some people around the world faced side effects and other negative physical outcomes after being injected with some of these vaccines.
Hundreds of drug companies, university research groups, biotechnology firms, and health organizations were developing therapeutic agents for COVID‑19 in various stages of pre-clinical or clinical research, from early 2020 through 2021. As early as March 2020, the World Health Organization (WHO), European Medicines Agency (EMA), US Food and Drug Administration (FDA), the Chinese government and leading drug manufacturers were coordinating with academic and industry researchers to speed up development of vaccines, antiviral drugs and post-infection therapies. Overall, it is clear that the science of making a medicinal drug, called pharmacology, is a complicated subject of study. Let’s talk about how a clinical trial proceeds for pharmaceutical interventions.
Around the world, pharmaceutical companies are the examiners that conduct clinical trials or clinical studies to evaluate the safety and efficacy of drugs that scientists are developing. These clinical studies are an essential requirement to achieve regulatory approval so the medicinal drugs can be made available to hospitals, pharmacies and patients to prevent and troubleshoot for communicable and non-communicable diseases.
According to the WHO, a clinical trial is: “Any research study that prospectively assigns human participants…to one or more health-related interventions such as drugs, biological products, medical devices and surgical procedures, to evaluate the effects on health outcomes“.
The process of clinical-trialing of a medical drug consists of a series of phases to finally conclude and ensure that the product is safe and effective at treating the relevant ailment or disease it is indicated for.
The following points explains the four major, standardized phases of biomedical clinical trials:
- Phase I – It usually tests new drugs for the first time using a small group of people as a human testing sample in order to evaluate a safe dosage range and identify its side effects.
- Phase II – It usually tests treatments that have been found to be safe in Phase I, but now needs a larger group of human subjects to monitor any adverse effects.
- Phase III – It is usually conducted on larger populations in different regions and countries to monitor wider specifications and features needed for a testing drug and also to identify its limitations. This is often the step right before a new treatment is approved.
- Phase IV – This step takes place after country approval and there is a need for further testing of a drug using a wide population over a longer timeframe.
Many Western countries engage in clinical trials to test medical interventions including drugs, cells and other biological products, medical devices, surgical procedures, radiological procedures, behavioral treatments and preventive care.
In accordance with ‘Guidelines on GCP Inspection‘ published by the National Medical Regulatory Authority (NMRA) of Sri Lanka, a ‘Good Clinical Practice‘ (GCP), which is an international, ethical and scientific quality standard for designing, conducting, recording and reporting of clinical trials, it is essential to ensure the protection of medical rights, the safety and wellbeing of study subjects and also to assure the integrity of scientific testing, study and conduct. The GCP helps to determine whether the clinical trials are conducted in accordance with the ethical standards and other applicable regulatory requirements, attention to the safety and integrity of trial subjects as well as good data quality.
Between 2008 and 2018, 210 clinical trials (63% of all applications) were registered with the Sri Lanka Clinical Trial Regulatory (SLCTR), while those registered trials showed an increasing trend over the years. All the registered trials were interventional studies, and a majority of 87.6% were randomized controlled trials. Several trials (9.5%) were identified as international collaborative studies. 70.9% Principal Investigators were affiliated to a university. 41.9% of the studies were self-funded by the relevant investigators. Details of ethics review committee approval were available for 96.7% of registered clinical trials. Conclusively, the regulation process of registering clinical trials for medical interventions have made a positive contribution to the emergence of a healthy and standard clinical research environment in Sri Lanka. (Source: Ten years of clinical trial registration in a resource-limited setting: Experience of the Sri Lanka clinical trials registry)
In the Sri Lankan context, clinical trials that require regulatory approval need to undergo regulatory review by the Clinical Trials Evaluation Committee (CTEC), the Sri Lanka Clinical Trial Regulatory(SLCTR), the National Medical Regulatory Committee (NMRA), and the Ministry of Health (MOH) and have ethics clearance from a well-recognized ethics review committee such as Ethics Review Committee (ERC), along with a no-objection certificate in prior to getting the letter of authorization for the conduct of such trial. Clinical trials must comply with the relevant government-approved protocols, applicable clinical trial regulations and relevant standard operating procedures. Compliance with these requirements provides an assurance that the medical rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are accurate and credible. Multi-centre clinical trials would be based on criteria such as nature of intervention, inclusion of vulnerable populations to trial, trial sites with more patients, facilities in the trials site, trial sites with more deviation to standard guidelines, and trial sites to which a complaint has been received. An internationally-aligned robust regulatory framework is essential to strengthen the health authorities at the competitive and vibrant global clinical research market, while ensuring the utmost safety of trial participants in the country. (Source: Guidelines for the conduct of clinical trials in Sri Lanka – Clinical Trials Evaluation Committee – National Medicines Regulatory Authority – Ministry of Health)
There are also challenges that still need to be vetted such as data security, ethical issues, indefinite timeframes, biases, predictions, failures to adhere relevant protocols, implementation in complex trial designs and ensuring proper training for target patients, particularly those who are agnostic to technology. A hybrid approach, with a combination of in-clinic and home visits, may be beneficial, depending on the trial requirements and would still offer cost savings and increased patient retention. The use of home-trial support vendors fits for some of the more complex procedures to be performed in the home, thus reducing the site burden. It would also reduce some of the burden on the patient as well. There is still work to be done to overcome the challenges and limitations, but the benefits to patients and sponsor companies can already be seen in the current offerings. Besides, siteless trials or virtual clinical trials will likely become more popular as the industry advances development of technology that will allow for a virtual approach. (Source: The Benefits And Challenges Of Siteless Clinical Trials)
In addition, a growing depth and complexity of contemporary health challenges have produced a range of difficult questions that cannot always be adequately addressed by relying on existing health policies, guidelines or codes of conduct. Debates over access to new and expensive pharmaceuticals and medical technologies, as well as increasing awareness of the gross health disparities which exist both within and between countries, have called attention to the need for a guideline of ethics around health policy and practice. Consequently, with reference to the current global pandemic, there is a great need for guidance to ensure ethical conduct of research, decision making in clinical care, and public health policymaking at each and every level. (i.e. Developing health emergency standard operating procedures for human research committees to facilitate rapid review of protocols during the COVID-19 pandemic)
Precisely, a clinical drug should be able to answer the questions; Do any of the drugs reduce mortality?, Do any of the drugs reduce the time a patient is hospitalized?, Do the treatments affect the need for patients to be ventilated or maintained in intensive care? – and, could such drugs be used by healthcare staff to minimize the patients’ illnesses and people at high risk of developing severe illness?. The journey of a drug from a laboratory into the human body is a complex process even a medicine could sometimes be toxic or overdosed to people with numerous illnesses.
Sachini D. Perera