Clinical Trials: Ethical Principles & Guidelines for Conducting Medical Research in Developing Countries
Clinical Trials: Ethical Principles & Guidelines for Conducting Medical Research in Developing Countries
Introduction
The Universal Declaration on Bioethics and Human Rights was adopted in 2005 by the United Nations Educational, Scientific and Cultural Organization[i].The adoption marked the final journey of years of debate and negations concerning issues on ethics in scientific and clinical trials. The declaration calls upon the UNESCO member states to incorporate bioethics and human rights principles as part of their national policies, regulations and national laws so as for the requirements to be effective[ii].This paper examines the value of the national declaration mainly on ethics of clinical trials and biomedical research and practices within the context of developing nations. The areas that are of relevant to developing countries are social responsibility and vulnerable persons among other ethical principles are presented. The paper further acknowledges the presences of other well-established bioethics principles that are applicable internationally. These are the guidelines by Council for International Organizations of Medical Sciences (CIOMS) and the Declaration of Helsinki by the World Medical
a) Historical background
Collaboration among all people of the world is it in terms of material assistance, trade and cultural interchange, will consequently help all peopleThe inter-global collaboration has, however, taken a different form especially, on the controversies concerning the distribution of benefits and collaboration among the people. The nations have the potential of occurring when nations involved have different ethical, political, economic, and cultural perspectives or when the nations are at different developmental stages[iii]. American medical researchers have for a long time carried out experiments on human subjects, but the mainly targeted ones are the vulnerable and poor. It is after the early 1990s that this unethical behavior stopped.
Currently, many of these researchers have shifted their focus to the third-world nations. This is especially in the study of the common infectious diseases facing the third world countries. These diseases include malaria, cholera, and AIDS[iv].Many of the third world countries have been struck by these diseases simultaneously, and it gives them the need to find a cure. Another contributing factor for the researchers from the developed nations, venturing into the developing nations is because of the strict regulations and high financial burden expected of them[v].These factors have made many investigators from drug companies and universities, to test new experiments in developing nations.
The various reasons and practices of the investigators have gone beyond the expected ethical and moralThe international codes on experimentation with human beings, such as the world Medical Association Declaration (1964) of Helsinki and the Nuremberg proclaimed principles 1947, all indicate that the subject’s well-being has to take the top priority and not the scientific the needed or the society’s interest[vi]. The ethical principle also call upon the need for physicians, researchers, and other investigators to first obtain an informed consent from the subjects before undertaking their study[vii]. Despite these codes and other standards past by western groups interested in clinical trials, many have not been under consideration in the developing countries. Most of the third world countries that are being used in these medical trials are does not afford the medicines that have been tested successfully.
The recruited subjects for these studies are seldom given the medical care expected of them as participants just like those in the developed nations. The current issue under bitter debate is on the issue of the application of the Western principle concerning clinical trials to the developing nations[viii]. This is mainly in the treatment of subjects from the Asian and African countries in the research studies. The debate mainly started after a 1994 research study known as the Pediatric AIDS Clinical Trial Group was conducted. This study is a university-based investigation that fund by the National Institutes of Health. Despite the study resulting to the provision of helpful information, on the prevention of HIV virus transmission from a pregnant woman who is HIV –Positive mother to the child, conflict arises whether this study was carried out ethically[ix].
The American investigators came to the conclusion that the provision of AZT to pregnant women who are HIV- positive during labor, during labor, and to the new born for a period of six weeks, the rate of the virus transmission will be significantly beThe researchers further showed that for those pregnant women who are HIV-Positive and did not receive AZT were likely to transmit the virus to their newly born babies. Among the ones who received the AZT, the chances of transmitting the virus is reduced by eight percent leading to an overall reduction of 66%. The use of AZT is now used in the prevention against the virus transmission from mother to child. The question arising from this study is that, were the researcher’s concerned on the issue of ethics in the provision of the drug AZT to the subjects[x].
This is mainly because this drug is associated with serious side effects. Their ethical stance is also questioned in how they address the possibility of one third of the pregnant women passing the virus to their newlyThe question, therefore, is that was it ethical to put the subject at a risk associated with the AZT drug that has toxic effects[xi]The findings from this study has only been applied in the developed countries, but, has not been adopted in developing countries with serious cases of AIDS. This shows that the global bioethical principles do not protect the human subjects used for research in the developing countries[xii].
b) Fundamental ethical principles of global bioethics.
The fundamental ethical principle on global bioethics has been endorsed based on the notion of sustainability, protection of human dignity, and the respect of human vulnerability and personal integrity[xiii]. The ethical principles show that they are based on the concept of conservation, future oriented, and peopleThe aim of the principles is to facilitate continuous improvement of the condition of human beings and to maintain various scientific and technological advancements for the benefit of all people in the present and coming generations. The goals of the global bioethics principles are as follows:
1. Respect for human vulnerability and personal integrity
The respect of personal integrity and human vulnerability are aspect that acknowledges the presence of the vulnerable individualism in the community. It is the responsibility of all human beings to protect those individuals who are considered the most vulnerable including the poor, the minority groups and the disabledAll individuals deserve to be respected, and their personal integrity as human beings should be respected. All people no matter their economic status, color, race, religion, age, and sexuality have to be cared. Any form of development should not be done at the expense of other groups; in this case, on the people from developing countries. The aim should be on sharing benefits from these developments equally and fairly no matter the difference of interests among communities and groups or between the affluent and the rich[xiv].
The main aspects that make many people in the third world countries to be vulnerable are limited resources, lack of sufficient medical care, environmental conditions, diseases, disability, limited educational level and personal conditions. The principles of vulnerability mainly apply within the ideals and values of bioethics and laws of bio scientific studies. This is mainly due to the issues that people who are vulnerable are more likely to be persuaded and convinced based on their human condition. Chadwick, Have, & Melin, (2011), show vulnerability is an aspect that defines the humanity ofIt is also an aspect that can be easily ignored when conducting scientific and medical developments and studies [xv].It is only until when a scientists or researcher takes into consideration the aspect of vulnerability that they will be able to adhere to the biolaws and bioethical principles expected of them. The respect and acknowledgement of the concept of vulnerability is, therefore, a call to protect individuals who are vulnerable based on their living conditions. It is a principle that should ensure that the dignity, integrity and autonym of individuals are protected, because most of the times these aspects are ignored or threatened[xvi].
2. Respect on human dignity
The main goal of bioethical developments is to use science in improving the quality of human life. When human life is improved and protected, the people’s self confidence is build and they will live a life of fulfillment and dignity[xvii]. The respect of human dignity in clinical investigations should play a central role[xviii]. This means that the researchers and investigators should first be required to conduct their studies after receiving informed consent from the human subjects. This means that the researchers have the duty to provide comprehensive information to their targeted participants or sample concerning the objective of the study, risk involved and how they will benefit in the study. The participant’s choice to quit in the process of the study should be respected. This shows the application of the concept of respecting human dignity in clinical trials[xix].
Vulnerability within the bioethical principle is involves the characteristics of human [xx]being based on their condition. Aspects such as integrity and dignity are also highlighted in the discussion on human vulnerability. The principle of human vulnerability is applicable in healthcare ethics[xxi]. Chadwick, Have, & Melin (2011), show that the conceptshuman vulnerability and personal integrity are principles that are morally binding. These principles are necessary in the advancement and for application of scientific knowledge and medical practices among other advancements that have an impact on human beings. Equity in science can be attained when the concept of human vulnerability is put under consideration[xxii]. This implies that individuals and groups considered to be vulnerable should be protected, and there is the need to protect their personal integrity.
3. Benefit sharing principle.
Research findings should be shared for the benefit of enhancing human development and growth[xxiii]. No human subjects should be used in a clinical trial if the benefit of the study will not impact on their lives directly. The participants in a research study should be compensated and appreciated for participating. For instance, on a study to test the effectiveness of a medication, the participants should be provided with free treatment if the drug is found to be effective. Also there is the need to compensate them for the risk they have undertaken in taking part in the clinical trial. For example, addressing the potential side effects caused by the drug[xxiv].
The principle of benefit sharing is the provision of profits, benefits and advantages to all human being through the use of human genetic resources to those who have taken part in a research study. The principle of benefit sharing applies to the concept of justice attainment among individuals who do not have access to a given product or service[xxv]. This is especially the case with research studies targeting people from the developing countries. The principle of benefit sharing guides in the maintenance of rules for distribution of benefits and to guarantee people from third world countries of theirScientific progress, such as the discovery of a medicine is a critical aspect for the third world countries health and social development[xxvi].
Therefore, the high income countries and the industrialized nations should be responsible in providing and promoting benefit sharing in the medical field[xxvii]. They are also responsible in promoting solidarity and International Corporation on scientific and technologies issues that impact on the third world countries. The concept of benefit sharing will help developing countries through promoting their health status, introducing the latest diagnostic modalities, and other new research findings[xxviii]. Sharing will also see that the developing nations gain accesses to scientific knowledge, technological skills, have access to capacity building facilities and gain supportive healthcare services[xxix].
4. Protection for future generation
Considering the sustainability of the principle of development, it is necessary to consider the risk that a clinical trial can have on a given group of people and their future. The technological and scientific developments have changed the ways of people’s lives and it more than never before, it has the potential of exerting more consequences on the lives of people in time and space, the analysis of people’s situation and to propose a sufficient solution should be the central goal of clinical trials. This is because; when these problems are not addressed there will be a general future burden and risks in the globe[xxx]. For instance, the HIV infection facing the Sub-Saharan countries should be addressed based on the best scientific findings to help stop the spread. For when this challenge is not addressed now, countries of the sub-Saharan Africa will perish and there will be nothing left for the future generation to come[xxxi].
Sustainability is only achieved when the risks as articulated consciously and areThe health problems facing the developing countries are global problems due to the idea that the outcomes of our actions presently does impact on the future. The health risks will impact on the developed nations and the future generations, and already have effects on the current generation in the developing nations[xxxii].
5. Social responsibility.
The principle of social responsibility has its roots from the sense of solidarity that started during the late 1960s among the international community[xxxiii]. The solidarity principle among nations has been transferred from one generation to another calling for all human beings to are and protect one another. Social responsibility is a call for globalAcademic institutions, medical companies and scientific educators should at all-time ensure that in the autonomy in making decisions, they should maintain proper balance of their power and the higher level of accountability[xxxiv]. They should be held accountable for effectively communicating to the members of the public concerning the mission of their projects[xxxv].
They are responsible for their commitment to excellence and quality in their research functions, scholarship and teaching. They have the obligation to protect and maintain the integrity of their research, scholarship and teaching from intrusions that are not in line with their mission[xxxvi]. The researchers should further ensure that they respect the fundamental human rights and ensure that the participants in the research studies are equally treated and not subjected to any form of discrimination. The research institutions should develop policies, and procedures that ensure equal treatment of the minorities, women, the vulnerable groups and the poor from any exploitative aspects and harassment[xxxvii]. The application of all the above bioethics principles in research studies and clinical trials act as a justification on the need to protect human subjects in this research in the third world.
General Ethical Issues In Clinical Trial Design In Developing Countries.
a) Randomization.
In a research study, the request for informed consent clearly acts as an indication that human autonomy and dignity are under consideration and respected. The interests of the participants should be respected by the researchers. The researchers from the developed nations should respect the needs and interests of participants from the developing nations. This is through ensuring that the participants are understood the implications and aim of the proposed research. This is vital for the participant’s education level is relativelyIn the developing and developed countries, the goal of providing appropriate education to the participants on the research will lead to the participants giving genuine consent[xxxviii]. However, the method of providing this information should also focus on the need to translate the information into the local dialects for them to understand. Some terms may however, lack the direct translations and definition of the local dialect such as the term, placebo. When randomization is the needed in the research, it will be vital to explain to the participants concerning the processes, as well as, the concept of equipoise.
Randomization is the process of assigning different interventions to the participants taking part in a clinical trialEach individual in randomization has an equal opportunity of falling into one group or another. Systematic assignment is different from randomization, since the participants are given a particular area of the study for various demographic, scientific, and clinical reasons. Such topics of research can be on genetic makeup, medical history, and age. Randomization is a process aimed at minimizing the inherent differences in group of individuals in different trail arm through randomly distributing individuals with specific characteristics. The method is done as a way of equalizing all factors which can be known or unknown by the researchers. The main support towards the method of randomization in an investigative study is that it minimizes biases in non-randomizes controls that obviously leads to unreliable result. Randomization is chiefly used in the evaluation of new interventions. Sometimes, however, trials on randomization may not be practical especially when there are a minimal number of participants. This will reduce the statistical power that is essential in making conclusions [xxxix]
In the third world Nations, researchers may convince participants that taking part in a randomized study might help them in curing a given disease[xl]. This might be aaspect but the problem is that the medicine has not been effectively tested for one to be sure that that drug provides cure. The Common Rule in clinical trials is that, the use of human subjects for research calls for the need to be careful especially when the involved persons are the vulnerable population. Informed consent should first be obtained before going on to select participants from a population comprising of children, the poor or the disabled people. In a study comprising of children, their parents consent is required[xli]. This means that the parents should be well informed about the study and to ensure that they do no misunderstand a single aspect concerning the research study.
The researchers should consider the conditions under which the intended population livesThis is mainly when undertaking a randomized-based study for placebo.
b) Standard of care and the use of placebos.
The main interests among many individuals in the developing countries have been the application of researches on human genome. This is mainly with the hope ofcure for diseases such as AIDS and malaria[xlii]. However, in the process of such endeavors, there is the likelihood of risks creation, such as, genetic discrimination or misusing of genetic resources[xliii]. The solidarity considers have to be undertaken so as to ensure proper care is taken, as well as, on the use of placebos. This is especially true in developing countries because most often there is the limited supply of technical and financial challenges[xliv]. Other contributing aspects that may interfere with proper care include limited training among professionals involved in these studies. This makes them lack the skills and knowledge expected in carrying out such studies. The main goal of the investigators and professional researchers should mainly be based on the need to protect individual taking part in the study and to disseminate knowledge[xlv]. They also have to put in mind the need to protect families, populations and individuals they affect in their studies. Another critical aspect that should be put into considerations the issues of distribution of benefits. This will prevent the exploitation of human genome for wrong reasons[xlvi].
Randomized controlled trials (RCTs) have a fundamental difference from medical based on the issues of risks justification, methods, andThe main goal of RCT is to examine the efficacy of treatment among a given group of people. The goal is to develop that will contribute to medical care improvement. Though participants gain standard or experimental treatment, the method of RCT is not a type of a personal therapy that targets the patients. The randomized controlled trials (RCTs) are mainly meant to test new or foreign procedures of medical care[xlvii] . RCT is a process that involves blinded assignment of treatment, randomization and there are no protocols that define the restrictive measures of the treatment. It is a method that involves tests and processes that are unnecessary in the medical field so as to achieve targeted and measurable results[xlviii]. Through the RCT processes that standard treatments under evaluation and the experimental intervention risks are justified on the basis that the benefits will be for the participants[xlix]. The risks are also justified on the basis that the expected knowledge value will benefit the research. However, the medical interventions risks posed to the patient in clinical trial can only be justified when potential benefits are guaranteed. This shows the benefits of having ethical principles applicable in clinical research[l].
The governing of clinical research through ethical principles will help in promoting the standard of care in RCT studies conducted in the developing countries. It will be wrong for researchers to think that the use of placebo controls is justified because there is no prove of a treatment being effective. Such a claim goes against the standards of care in medicine[li]. Recent revisions on the codes to guide research studies have been made as for the case of the international ethical Guidelines and the Declaration of Helsinki[lii].
c) Protecting confidentiality.
A person’s confidentiality and privacy is also another aspect that the needs to be respected in clinicalThe International Bioethics Committee of UNESCO (IBC) indicates that the personals information provided in a research study has to be respected[liii].The committee further calls for the need of protecting personal information to the greatest possible level. This information should not be disclosed or used for other unintended purpose beyond the actual reasons of its collection and the people consenting to. Otherwise, discloser or misuse of this information is contrary to the expectation of the international law, especially the international human rights law[liv].
The obtaining of informed consent from subjects on the control trial assures the investigators that they are undertaking a clinical research that has ensured that the participants are fully aware of their preferences, interests, and values. The trialhave to be accurately informed concerning the benefits, risks, protocols, alternatives, and purpose of the study[lv]. In informed consent respect of people’s autonomy plays a significant role. A proxy decision maker should be chosen in case where a study involves individuals with limited ability, such as, mental challenges, and unconsciousness, or in case where children are the targeted group of the study[lvi].
The application of ethical consideration does not come to an end after obtaining informed consent. Instead, the information should be respected throughout the process andThis means that any data collected for a research study should be confidential. The subjects undertaking the study should be given the liberty to withdraw or change their mind in the process of the clinical trial without being held liable. The participants should constantly be updated whenever new changes occur and with information involving the clinical and intervention condition[lvii]. The main priority for the researchers should maintain the welfare of participants at every stage of the trial. Any adverse effect during the process has to be keenly considered and taken care of adequately. Finally, the participants of a clinical research should be informed of the findings or outcome of the study without hiding anything[lviii].
Investigators should also be aware that through assuring people of their confidentiality and proving the promise, they will be able to gain more people willing to take part in the study. The researchers according to Sugarman (2002) should know that it is their responsibility to maintain the confidentiality of people’s information because certain kind of information may pose a social or legal risk to the participants. Through maintaining the confidentiality of participant’s information they are more likely to achieve a good rate of participants and to eventually get reliable data [lix]
d) Selection of participants.
The selection of participants also presents another ethical consideration in carrying out a clinical study. The principle of participant’s selection in bioethics first came in to picture in newspaper accounts of 1972. This was a study conducted on a group of African American men to evaluate the prevalence of syphilis. This is the Tuskegee Syphilis Study conducted among 399 African American men. The study had 201 controls and it began in 1932. However, the study was questioned for violating a wide range of ethical concerns. The first was on the issue of selection. It only chose a group of men from a poor farming community as the study’s site despite the researchers knowing that this was not the only community having a high prevalence rate of syphilis[lx].
The researcher’s presumption was that the research subjects would benefit from the procedures of the study. This means that the participants would benefit from the therapeutic value of the study, as well as catering for their funeralThe researchers’ despite proving that the treatment by use of penicillin was effective in treating syphilis, they did not effectively treat the participants. In 1974, the National Research Act was passed in the United States following the unethical aspects that characterized the Tuskegee Syphilis Study[lxi].
The law presented a regulatory approach for guiding ethical research dealing with human participants. The law called for the need to protected human participants in Behavioral and biomedical research[lxii]. Other additional requirements for these studies have been made to address valuable ethical principles such as justice, beneficence, and respect forJustice mainly plays a central role in the selection of participants since any research findings should be responsible in providing participants with their desired benefits[lxiii]. Another aspect related to justice in the selection of participants involves their vulnerability, as seen in the above the selected ones were the disadvantaged in the society[lxiv]. Other vulnerable people in the community involve the mentally retarded, children the poor, and the institutionalized. These people according to the international human law should be protected. It will also be unjust to select a group of individuals with devastating illnesses for clinical trials when there are no options for treatment[lxv].
Ethics In The Research Process/Application
a) Obtaining Voluntary Informed consent.
Whenever there is clinical equipoise, the most valuable thing is to realize the existence of ethical challenges associated with clinical research studies that make use ofThis is mainly because of the close relationship of research to clinical care[lxvi].In many circumstances, obtaining a valid informed concept becomes a challenge. The targeted patients being targeted for research may not know the difference between research and clinical care[lxvii]. They may not be aware their clinical are is selected via randomization and not that their physicians have chosen them. This is the common misconception that exists in many clinical studies[lxviii].
Based on the practical issues involved in getting informed consent and adequate enrollment in clinical studies based on randomization, there are other proposed alternatives known as; Zelene randomization, pre –randomization, and randomized consent. These alternative methods deal with the assigning of a treatment arm to potential participants before obtaining their informed consent. Though these methods have been found to solve the challenging design problem, many have seen them as being unethical and unnecessary[lxix]. In some cultures, the issues of informed consent and randomization may be applicable because individuals believe that they should not venture on issues that they are uncertain[lxx]
Informed consent is more of a process from an ethical perspective and not simply the completion of a form. This process involves three main activities which are the threshold stage, provision of adequate information and obtaining consent. The first threshold step calls for the need of the participant to provide informed consent on the basis that he or she has the capacity and competency in making decisions[lxxi].
The decision to participate this should be at their personal will and choice. When the potential participant has agreed to be part of the clinical research, he or she is providedthe right information on concerning the study. The information should be made simple to understand and also translated in a language that can best be understood by the participant[lxxii].
The final stage is applicable to those agreeing topart in the clinical study. They should do so by expressing their decisions and through signing a document on informed consent[lxxiii].Various obligations arise within this model of informed consent. First is that the researcher has to evaluate and verify the capacity of potential participants to make decisions. When this becomes questionable, they also have to evaluate the participants understanding level, which is a vital aspect in making of choices[lxxiv]. It is useful for researchers to review evaluations of other alternative approaches and their efficacy[lxxv]. Also, in the process of obtaining informed consent, the issue of openness has to be addressed. This will give individuals a chance to be assured and believe that they will directly benefit by being a participant in the research study[lxxvi].
b) Involvement of the Community and Study Participants in the Design of Research.
A clinical trial that is sponsored by a developed nation has to be acceptable in the source and host countries the guidelines by CIOMS indicate that the ethical guidelines that are relevant to the source guaranteed should be ethically acceptable in a host country[lxxvii]. This indicates that the ethics committees of the host countries have the responsibility on matters related to the clinical trial including the design of the research. The community members and study participants targeted will take part in the acceptance of the proposed study before providing their informed consent. The ethics committee has to ensure that the ethical standards of the study are as per the needs of their country[lxxviii]. This is because the host country committees do understand better the moral and cultural values of their population that the proposed research targets.
The implications of the argument is that the design of a study can itself bebased on ethical consideration of the targeted country, but, might not be considered in another country[lxxix].
Many third world nations have been faced with concern ofethical standards by sponsoring countries. This is mainly because the sponsors the need to be satisfied with the research ethics of the projects that they are funding. However, the forgotten group is the community members and the targeted participants. They should have a say concerning the designs of study that impact on their values and the needs. The research design of randomization might not be applicable to certain communities because they do not believe in uncertainties[lxxx]. Reconciling these kinds of disagreements chiefly lie at the heat on the underlying set of ethical principles on the need to protect human dignity and autonomy [lxxxi]This guiding principle is necessary in making any argument on a proposed study design to be ethical or not. The guidelines passed by the Declaration of Helsinki should be used in ensuring that the communities and participants have the independence to decide on what is right for them and what is not[lxxxii].
c) Assessment of Risks and Benefits.
Sound ethical standards should be in place whenever potential harm and risk in clinical research is anticipated. These ethical standards have to be carefully observed no matter the economic or geographic setting under which the clinical trial is being conducted. Many developing countries however have under-developed procedures and mechanisms meant for the review of ethics. Kennedy (1999) suggests that the international biomedical guidelines and the declaration of Helsinki are useful and necessary. These guidelines, however, have some weaknesses that have to be addressed. These international guidelines only address the trial participant’s interest, whenever there are resources and training for the implementation and interpretation of the research study[lxxxiii]
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