The human race seeks to maintain health and sustain life by constantly ensuring dynamic equilibrium between the internal body systems and the external environment. The World Health Organization (WHO) defines health as a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity. This definition takes cognisance of the influence of physiological, psychological and social factors on health and illness, as well as the interactions between these factors. It also brings into perspective health as a human right, which places demand on physical and social resources for its sustenance. Economic growth and development though a stimulus for well-being, is not without disadvantages. For instance; it leads to environmental concerns such as noise pollution, overcrowding, loss of natural habitat and biodiversity as well as depletion of the global resources and the impact of global warming. Industrial development often impacts negatively on health. Sustainable development should be accompanied with evaluation of both the positive and adverse effects and minimize the latter. There is a tripartite relationship between the physical environment, biological environment and the nature and scale of human activities. These require balancing. There is need to update knowledge on health continuously, as there are changing phases of development.
This can be facilitated by research.
There are many infective agents, which include bacteria, viruses, fungi and parasites. Control measures had effectively kept many of the resultant communicable diseases in check, until in recent years with emerging and re-emerging infections; some affecting people in many nations causing pandemics. Research had contributed to successes of the control measures. What is a virus? A virus is a microscopic particle that can infect the cells of a biological organism upon which they are dependent for replication and survival. They cause such common and often minor ailments as common cold, the flu and chickenpox, and more serious diseases such as Ebola, Bird Flu, AIDS and Severe Acute Respiratory Syndrome (SARS). This brings us to the topical COVID 19. Coronaviruses belong to a large family of viruses, which may infect animals and humans. The coronavirus that causes the current pandemic, known as COVID-19 is said to be unknown before the outbreak in Wuhan, China in late 2019 (the origin of the appellation).
Debates point to the fact that the infection is a result of man’s activities on the environment, even if inadvertently so. Industrialization and globalization got the virus across the world within a short time. While COVID-19 is no respecter of anyone, certain variables seem to influence susceptibility and outcome. There are indications that children and adolescents are not spared from being infected but evidence shows that they are not as likely as adults particularly the elderly, to develop severe disease. Occurrence of underlying medical conditions such as diabetes, heart disease and cancers makes outcome of infection unfavourable. It is therefore important for everyone to follow the same guidance on self-quarantine and self-isolation, based on possibility of an exposure to infection or if they are showing symptoms. This fact makes it necessary for children to avoid contact with older people and it would not be necessary to visit grandparents at this time, even if they are missing them! A person may contract the virus without having symptoms such as fever, a dry cough or shortness of breath but is capable of transmitting the infection. Some may have mild symptoms and recover without knowing. Various tests are available to confirm infection such as taking a swap from the back of the nasal cavity and analysing the sample in the laboratory to see if it contains the virus. They are offered to people who have symptoms, other risk factors or have been exposed. Cure is determined after testing negative twice.
Research helped to identify the mode of transmission, which is primarily from person to person through small droplets expelled from the nose or mouth when someone with COVID-19 coughs, sneezes or speaks. People can contract COVID-19 if they breathe in these droplets containing the virus but since the coronaviruses are relatively heavy and do not travel far before they sink to the ground, maintaining social distance of at least two metres prevents one from contracting the infection. Wearing the correct masks appropriately can also reduce the risk of spread. However, at a lesser risk, the droplets can fall on objects and surfaces around the infected person; such as tables, doorknobs and handrails from where they can be picked up by other people who then get infected by touching their eyes, nose and mouth. For this reason, proper and regular handwashing with soap and water or cleaning with alcohol-based hand rub is an effective preventive measure. Surfaces should be cleaned with soap and water followed with disinfectants and people should avoid touching their faces with their hands. Fortunately, this virus does not live long on inanimate objects. Its lifespan depends on the materials the surface is made from and it varies from a few hours on aluminium example; drink cans, to a couple of days on glass like tumblers and windows, ceramics like dishes, stainless steel like pots, plastic like bus seats, wood like furniture and metal like doorknobs. Coronavirus may not live as long in higher temperatures and humidity as in cooler and drier environment. WHO has continued to assess ongoing research on the ways the virus spreads.
Policies and guidelines are based on research findings and are reviewed as more facts emerge. Misinformation, panic and fear should be avoided. Individuals are encouraged to obtain accurate information through authentic sources such as WHO platforms and the Nigerian team in charge of the pandemic; comprising the Nigerian Centre for Disease Control (NCDC), Presidential Taskforce (PTF) on COVID-19, Federal Ministry of Health (FMOH) and Development Partners. COVID-19 has caused lots of suffering and deaths, destabilized global economy, forced restructuring of the society including educational systems and changed some value systems; which though may be positive. It heated up international polity, exposed inequalities and those gaps that are being addressed in the 2030 Agenda for Sustainable Development. It had a huge toll on many other aspects of human lives and overwhelmed the health systems. The Government, various organizations and individuals contributed to the stimulus packages but not in a systematic manner. There is a need to expand and introduce a more robust and systematic social welfare system.
Meanwhile it was argued that the negative impact of the solutions proffered should not outweigh the disease itself. Policy-makers and Scientists are falling back on history and lessons learned from such pandemics as the Spanish flu of 1918, for the way forward.
What is a research? According to the American Sociologist Earl Robert Babbie, it is a systematic inquiry to describe, explain, predict and control the observed phenomenon. It is usually designed to answer certain questions or solve a problem. Epidemiology as defined by the Centres for Disease Control and Prevention (CDC), USA, is the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems. Information is provided on the number of cases and related to the size of the population or sub-population as rates; and the pattern of occurrence by time (such as hourly, daily, weekly, seasonal, annual, etc.); place (in terms of geographic variations, urban/rural differences, etc.) and personal characteristics such as demographic factors (age, gender, marital status, socio-economic status, and behaviours) which may be related to the risk of the disease. Studies also provide information on why and how the disease occurs. All these are applied towards prevention and control.
Clinical Trials: As a type of research, a clinical trial studies new diagnostic tests, treatments and preventive measures for their effects on human health outcomes. This includes testing medical interventions such as drugs (including traditional medicine), vaccines, behavioural treatments and preventive care.
The collaboration of the Centre for Research in Traditional, Complementary and Alternative Medicine with WHO, the Nigerian Council of Physicians of Natural Medicine and other traditional medical practitioners on integrating Traditional Medical practice into healthcare systems is apt. Clinical trials are also required for old drugs which are being proposed for a new condition; known as drug repositioning. This is the situation with such drugs as hydroxychloroquine, chloroquine and several others for COVID-19 treatment. This option has become necessary with no vaccine or readily available medication and with the urgent need for intervention. Also, development of a vaccine may take more than a year and novel treatment requires even longer, based on the need for compliance with the Phases of Clinical Trials. WHO recently announced the trial of four drugs and drug combinations in treating COVID-19 with the aim of comparing their effectiveness.
Clinical trial requires a carefully written protocol that is approved by a designated committee. In Nigeria, the National Health Research Ethics Committee (NHREC) accredits independent and institutional committees, and collaborates with the other regulatory body National Agency for Food and Drug Administration and Control (NAFDAC). The Health Research Ethics Committees (HREC) review mainly the ethical aspects of the protocol particularly as it relates to research participants. Additionally, HREC monitors compliance with the approved protocol. For international trials, the protocol must pass through ethical review and be approved in both the country of sponsorship and at the research sites. Based on a promising result from laboratory animals and experimentation with human cells, clinical trials are performed in 4 phases, beginning with few human research subjects and gradually increasing the number of participants. Each phase builds on the results of previous ones. Phase I is particularly to establish the dose and test for safety of the drug. Phase II recruits more participants and it establishes safety further, as well as efficacy and monitors adverse effects. Phase III involves a large population of participants who may be assigned to different treatment groups for comparison.
The outcome determines whether the medical intervention (in this case drug) will be approved for use by the general public or not. This aspect is vital for the protection of human health. The use on the public, of any unapproved drug or other medical interventions is illegal and dangerous. The last is Phase IV, which is conducted among a large population after approval and release of the medication. It lasts long and allows time to detect side effects and safety concerns further. These phases can take place at multiple research centres, coordinated by focal persons. Using large number of participants; that is, a robust sample size, and comparing results from many separate studies that adhere to the same protocol gives strong and convincing evidence. Nigeria has joined several others on the solidarity drug trial to help find an effective treatment for COVID-19. The data collected and the results reported must be accurate and credible.
HUMAN SUBJECTS’ PROTECTION
Research on human subjects with the ultimate to influence better health outcomes, had initially been performed without specific international, regional and national policies and guidelines. There were no formal considerations for the health and rights of research subjects, until abuses were reported and investigated, over five decades ago. Historically, the principles of protection of human research subjects were first developed as the Nuremberg code in 1947 when Nazi war criminals were tried. These basically comprise Volunteerism with an Informed Consent to participate in research, Favourable risk/benefit analysis to prevent harm and the Right to withdraw from research without repercussions. The Nuremberg code formed the foundation for the current systems of human subject research oversight and protections worldwide. For instance; The World Medical Assembly established the Declaration of Helsinki in 1964 with guidelines that recognize the establishment of an independent committee charged with the review of research protocols and includes that “research with humans should be based on results from laboratory animals and experimentation”. Other ethical considerations for human research subjects include Beneficence meaning protecting the well-being and respect for persons, thereby, maximizing the benefits of the research, minimizing any possible risks and ensuring that the risk does not outweigh the benefits of the research to the subjects and others.
Selection of Study Population: In research with human subjects, processes are put in place to ensure standards and safeguard the rights, safety, well-being and confidentiality of the participants. Selection of the study population is important to the extent that they must be able to access the treatment and the inherent benefits that accrue eventually. This means that it would be wrong to test a drug or vaccine among a low socio-economic group who may not be able to afford the product subsequently. In this respect, clinical trials may not be carried out only in developing countries where the population may not be able to afford the product eventually. In addition, selection of study populations should be based on justice, with equal distribution of the risks among all classes and race. A recent revision of the Declaration of Helsinki in 2013 recognizes this and states that provisions for post-trial access be made for all participants and it must be disclosed to them during the informed consent process. Therefore, it would be expected that the products may either be sold at a subsidised rate or even donated to poorer nations that took part in the trails. The recruitment of vulnerable groups such as incarcerated persons and those in low socio-economic class must be justifiable and strictly based on the objectives of the clinical trial. Pregnant women and children are only included in trials that specifically address them. Following approval of the protocol, the recruitment of individual participants is also carefully guided.
Informed Consent: This brings up the concept of informed consent, which is a process by which a person voluntarily agrees to participate in a research after being fully informed. The content of the information should include risks and benefits of the research, the procedure and possible duration. The subjects must be given opportunity to ask questions and seek clarifications. In addition, the subjects must be reassured that they can withdraw from the research at anytime without any repercussions to them. The high level of illiteracy in the country makes it difficult to effectively communicate to the participants the concept of research, clinical trials and their processes but this must be circumvented and their understanding must be ensured. Other factors that affect competence to give an informed consent include maturity and rationality. The legal age at which a participant can give consent varies between countries and is commonly 18 years. If the person is a minor or of such conditions as unsuitable mental state, a legal representative may give permission for the individual to participate in research. All the processes of obtaining consent must be documented. Thumb printing can serve as an alternative to signature, so also witnessed audio recording.
It is important to note that the agreed reimbursement for transportation and lost wages to participants should not be tantamount to undue inducement or subtle coercion, in which case they would be too blind to make an informed choice of whether to participate or not. Arrangements must be made for ancillary treatment, in which clinical conditions in a participant though unrelated to the trial, is discovered during its course and should be attended to. There must be regular safety monitoring. While trial is ongoing participants must have access to a medical personnel on the team, as well as identified alternative medical services, should they develop any adverse reactions. They should not be made to pay for treatment of those adverse reactions. Compensation plan should be put in place should injury associated with the clinical trial occur, and the recruited participants in clinical trials may possibly be insured. There must be openness by the researchers and participants must be able to seek clarification on their concerns and take decisions on when to withdraw from the trial. The research protocol should have also indicated the conditions for early trial closure.
Respect & Confidentiality: The participants must always be treated with respect and reassured that their participation in the trial though voluntary, is highly valued and appreciated. Throughout the processes of clinical trials and after closure, confidentiality must be ensured, in order to protect participants from potential harm such as psychological distress, stigma and damage to social standing, etc. There should be no breech of ethical principles at any stage of the trial and beyond. This is the ultimate responsibility of the Lead Researcher/Principal Investigator. It is good to provide feedback to the clinical trial participants.
With international collaborations in research and development and eventually with a high proportion of the population being immune to COVID-19 (termed herd immunity), leading to indirect protection of others who are not immune, it is hoped that COVID-19 pandemic would be put under control, even if it is not eradicated soon. Research is essential for scientific advancement therefore standards must be maintained to provide assurance that the rights, safety, well-being and confidentiality of trial participants are protected. The need to prioritize health and increase funding of relevant researches by the Government, Development Partners, Corporate and Private agencies as well as individuals cannot be overemphasized, as this will go a long way in promoting good health and well-being. Additionally, it would enhance the attainment of other Sustainable Development Goals. As stated by the UN Secretary-General António Guterres, “We need to turn the recovery into a real opportunity to do things right for the future. Health systems should be strengthened” Collective effort is the ultimate and the time for change is now.
*Prof. Margaret Olabisi Araoye (MBBS, MPH, FWACP) is the Provost, College of Health Sciences, Prince Abubakar Audu University (former Kogi State University)
Anyigba, Kogi State. E-mail: email@example.com