Center for the Right to Health (CRH) is a non-profit, non-governmental organization, which is concerned with improving the standard of healthcare in Nigeria using the human rights paradigm. It is committed to empowering vulnerable people like people living with HIV/AIDS, women, children and youths to assert their right to health.


© CRH publication, July, 2002 All Rights Reserved


No part of this publication may be reproduced or transmitted in any form or by any means without the written permission of the organization. For further information and enquiries, please contact:

Center for the Right to Health (CRH)
3, Obanle-Aro Avenue
off Coker Road Roundabout
Ilupeju, Lagos, Nigeria.
Tel: 234-1-7743816
E-mail: mailto:crhaids@yahoo.com,iwuagwus@yahoo.co.uk


This research is carried out with support from the Ford Foundation Office for West Africa.

For over three decades, man has continued to engage in scientific research for drug development or biotechnological purpose. However the critical issue in the conduct of the se researches is the ethical consideration of such research especially when human being are involved. Many a time the outcome of the research has often been loss of lives or deformity experienced by human beings that participated in such experiments. Worse still many of the participants may never have been informed or have a clear picture of what they were going into. Examples abound of the negative outcome of biomedical research.

As far back as 1900, the Prussia vaccination trials were conducted on poor and vulnerable people without their consent thereby causing grave havoc to their lives. The great loss of human lives at the Tuskegee, Wiillbrook and the Allan Memorial Hospital are a mere reminder to us of how research can go wrong and cause inconsequential havoc to humanity.

But perhaps the gravest wound ever inflicted on humanity was the horrific experiments conducted on human beings by German doctors under the Nazi regime during the Second World War. That experience has left a dent in our mouth till today. Several lives were lost in crude circumstances

Here in Nigeria, the case of Pfizer, a drug company in Kano, which conducted experiments on human beings with meningitis and the loss of lives recorded sometime ago is still fresh in our memory.

Our country, Nigeria has witnessed a high prevalence of HIV/AIDS of 5.8% as at 2001, translating to 3.47million people already infected. Most People Living with HIV/AIDS [PLWHA] look forward to the discovery of a cure for the virus. All hands had been on deck to discover a cure for HIV/AIDS. Both orthodox and unorthodox medical practitioners and scientists have been working hard to find a cure and there had been many claims of discovering a cure. This led to a clinical trial of some of these drugs to verify how genuine these claims are most of the drugs purported to be herbs.

Many People Living with HIV/AIDS [PLWHA] who were recruited for this purpose reported to the Center for the Right to Health (CRH), alleging unethical practices in relation to the trial. Many complained of severe side effects that they did not anticipate neither were they consistently given medical treatment for the side effects. Some felt coerced by their desperation for cure, lacking full understanding of what they were volunteering for. Many complained that they were not treated in dignity.

It has therefore become necessary that a publication of this nature be produced to educate the public and in particular PLWHA- who might be willing to participate in future trials on the ethical and human rights issues raised by drug trial. It is written in simple language to empower PLWHA and others on their rights in clinical trial.

A clinical trial is a process whereby vaccines or drugs such as HIV drugs, are made to go through various tests ensuring they are safe and effective for humans.

When a drug company develops a new medication the process starts in test tube and animal studies. These studies which give researchers an idea of how well a medication works and what kind of side effects it might have in human is referred to as the pre-clinical trial. If the result of early studies look good, the drug company or researcher designs and pays for clinical trial to test the medications in humans.

These trials are divided into three stages, namely:
a. Phase I
b. Phase II
c. Phase III

PHASE I

This is to find out whether the treatment is safe: It usually involves small group of volunteers, who may either be HIV positive or negative. There is usually a high risk to volunteers at this stage since this is the first time the vaccine or drug is being tried on humans. It lasts for a few months.

If you enrol in a phase I trial you may have to spend some time in hospital for close monitoring of drug levels in your blood. There are usually no direct health benefits from participating in a Phase I trial.

PHASE II

This phase finds out whether the treatment will work. Participants are in the range of hundreds. The risk level is moderate. It may be for about a year.Phase II studies assess whether the treatment is active against the disease in the short term by looking for changes in viral load and CD4 count. If the treatment is not active, no more trials will take place. Phase II trials usually last for at least six months. If you enrol in a Phase II study you will need to attend the clinic on a regular basis for blood tests and other monitoring.

PHASE III

This phase finds out the ability of the treatment to protect against HIV/AIDS Infection. The risk level is low since at this stage more information about the safety and effectiveness of the drug is known. The period may be up to three years. It usually involves several hundreds of participants.

Randomisation
This is an essential feature of almost all clinical trials. Everyone who joins the trials will be assigned to one of the treatment groups at random, usually by computer. This is the best way to make sure that people in different arms of the trial are broadly similar, so that reliable comparisons can be made between the effects of the treatments used in the different trial arms.

Comparison trial
The most common type of clinical trial is a comparison trial. This is a trial in which one group of people who receive a new treatment is compared with another group of people who receive an existing or standard therapy. When there is a recognised standard treatment for a particular condition, then trials will be designed to compare an experimental drug with that standard treatment. In this case it would be unethical to give some trial participants no treatment rather that the standard treatment.

The detailed plan for a trial is called a protocol. It lays down procedures for how the treatment will be given, who is eligible to take part, the timetable for tests and visits for participants, the length of the study, how the results will be assessed and so on.Before a study can begin, an ethics committee responsible for each clinic that wants to run the trial must approve of the protocol. The members of the ethics committee may vary, but usually include doctors, nurses, at least one lay-person (especially from the target group) and often a lawyer or clergy. They are responsible for protecting the rights and interests of the people in the trial, and work independently of those running or financing the trial.

The protocol is usually prepared by a group of doctors or researchers. The planners of the trial will first examine previous research that has been carried out concerning a particular experimental treatment.Then they would work out the remaining unanswered questions and design a new trial with the aim of answering these questions.

The next step is to recruit participants and start the trial. The more quickly participants are recruited to the trial, the sooner it can be completed and the treatment’s benefits and risks can be assessed. The difference between the effect of a new drug and another treatment could be small. The drug may have to be tested in a large number of people to get a clear picture of whether it is better, as good as or worse than other treatments that are currently available.

So, a clinical trial, for example is more or less as a partnership between researchers and People with HIV. Researchers need people to join their trials so that they can improve medical knowledge about HIV infection. People with HIV may want to help this research, but will also want to make sure that their individual interests are being looked after in the trial.

Each clinical trial has its own rules about who can and who cannot take part. These are known as inclusion and exclusion criteria, or eligibility criteria. The inclusion criteria spell out the characteristics that will allow a person into the study. This is to make sure that the people in the trial are similar enough so that it will be clear which groups of people might benefit most from the new treatment. Trials of new treatments are usually run in several different groups of people at once in order to build up a bigger picture of the way drugs should be used best.

For example, a particular trial might aim to test the effect of a drug for people who are at a particular stage of HIV disease. So a typical inclusion criterion might state that participants in a trial have to have a CD4 (T-cell) count between, say, 220 and 320, or a viral load above 10,000.

The exclusion criteria are intended to protect the trial participants. For example, you may be excluded from a trial if there is a risk of a dangerous interaction between the trial drug and other treatments that you use. A common exclusion criterion forbids trial participants from taking other drugs at the same time, which are similar to the one being studied. For example, people in a trial of a Tuberculosis drug will not be allowed to take other Tuberculosis drugs while they are on the trial.

Trials sometimes exclude whole groups of people. Most trials exclude pregnant women, because of a fear that the treatment might harm the unborn baby. They also exclude women who are breastfeeding because the drug might be passed onto the child through breast milk. Most trials insist that women are using contraception.

There may be many reasons to think about participating in a clinical trial. In deciding whether or not to participate in a clinical trial, you may want to consider some of the risks and benefits of such a trial.

SOME POSSIBLE BENEFITS

1. A clinical trial can help you gain access to an experimental medication, which may improve your HIV infection level. This is particularly true for people whose viral load is high and their T-Cell count low. As a result of the trial, a medication may be discovered which might lower your viral load and raise your T-cell count, and improve your health. You will never get such benefit if you did not try. Nothing ventured, nothing gained or lost.
2. Trials also afford patients the opportunity of having one-on-one contact with a doctor in a trial; you are likely to develop a relationship with the research team. These professionals will be involved in his care. This will not affect your appointments with your regular doctor. It will only mean that more hands are attending to you.
3. You will receive comprehensive information about HIV/AIDS transmission and how it can be prevented. Also, you will get extra first hand information on how best you can help your situation.
4. It will make you have access to HIV/AIDS prevention methods, including male and female condoms and other facilities.
5. There is likelihood of your receiving compensation for time, travel and inconvenience for participation in the trials.
6. If the trial succeeds, an effective protective immunity to HIV/AIDS may be developed, and you will be remembered for your noble role.
7. Some people participate in clinical trials because they want to help others with HIV. This is true in the sense that participating in a trial may lead to the development of new medications for HIV/AIDS.

POSSIBLE RISKS

1. There is likelihood of the participant developing unpleasant side effects to the tested medications. This is worst in the case of the Phase I trial, as necessary information about the safety of the medication is not available for participants.
2. It requires a HIV positive person for each trial and if one moves from a previous (former) drug to a new drug trial which is not efficient, there are risks that the infection will rapidly become worst increases and possibly, development of resistance to the former drug may occur.
3. Trial may require that several injections be given over months or years, resulting in pain, occasional skin reactions, and possibly other biological adverse effect, such as fever and malaise.
4. Injuries may be sustained by the participants due to research activities during the course of the trial.
5. Participation if publicized may attract stigma and discrimination to participants.
6. Participation at trials may cause anxiety, stress, depression as well as depression between partners in a relationship.

It is usually advisable for you to pause a moment and ask questions about your rights before joining a clinical trial. Many people who are made to participate in clinical trials know little or nothing about the trial. Some are forced to join without having the benefits of the information about their rights during the trial. It is important that a person intending to join a clinical trial must have his voluntary consent obtained before the trial. This implies that decision to participate is based on full knowledge about the trial. You need to know the implications of taking part in the trial. It is advisable that the research team designs an informed consent form. Such form should contain full information about the trial, written in easy to understand language (where necessary in vernacular).

As regards HIV/AIDS related trial, the following principles are relevant:
a. Informed consent
b. Confidentiality
c. Equitable access to information and benefits arising from the trial.
d. Protection from discrimination.

a. It should contain information that the study involves a research and the reason for the research. It must state the duration of the trial and the procedures that will be followed at the trial.
b. There should be a description of possible risks or discomfort to participants.
c. It should also describe any possible benefits to participants.
d. It must clearly describe to the participants all other alternative treatment or options open to him if he decides not to participate at the trial.
e. It should describe how the confidentiality of the participants would be protected.
f. It should describe to the participants the payment of compensation and who bears the expenses in the event a participant is injured during trial.
g. The participant have a right to keep a copy of the informed consent they have signed.

This is to enable them review it later on, they would make an informed decision to continue the trial.

First stage - when a candidate is being screened for eligibility to participate at trials , informed consent should be obtained during this screening process after the candidate has received all material information regarding procedures to be adopted during the trial. Full informed consent should be given for the test for HIV/AIDS status which should be accompanied by pre-and post-test counseling.

Second stage - consent is required once a person is judged eligible for enrolment to participate in a trial. Such a participant needs to be given full information concerning the nature and length of participation in the trial.

Note that the consent to be obtained is that of the individual who is willing to participate and not of a third party. No one should give consent on your behalf. The law does not recognize such. Except where the person involved is an infant or young person. This may not be necessary as they cannot be involved in a trial.

It is necessary for you as a participant in a trial to ask question if you are not satisfied with the procedures. Do not hesitate to get in touch with the organizer of the trial if there is anything that is not clear to you. Some of the questions you may want to ask are listed below:

· How often do I have to visit the venue of the trial and for how long will I stay?
· What are the immediate and long term side effects of this drug ?
· Does the informed consent form contain all the risks and benefits of the trial?
· What should I do if I get sick or get bad side effects while participating in the trial?
· Will the lab test cost me anything?
· Will I get the result of the test?
· Can I use the prescription drugs while I am in this trial?
· Can I take other experimental drugs?
· Will I get paid for participating in the trial?
· What is the fate of my family if things go completely bad (death)? Are there any insurance policies?
· How can I find out about the result of the trial?
· You can also solicit for advice and support from AIDS service and human rights organisations.

You are not expected to pay any money for accepting to participate at a clinical trial. Most of the medication and tests to be carried out during the trial are free. If you are asked to pay money for test, ask questions about it and make sure you understand this issue properly before joining a trial. In most situations, participants are paid for taking part at trials. There are different reasons why a participant may be paid for taking part in a trial.

· For Your time Some trials may take a great deal of your time. At times you might need to stay over night in hospital for a trial to be conducted.
· For an Uncomfortable ProcedureSome trials require multiple blood draws, X-rays, pap smears etc. You may receive compensation for your discomfort if you consent to such procedures.
· For Taking Risks You might receive compensation for taking the risk to participate at a trial. This is more so if there is little or no information available about the treatment to be provided at the trial. Funds are also expected to be made available to cover your feeding and transportation expenses during the trial.While considering the compensation you are entitled to for taking part in a trial you must also think about your health. The most important thing to you should be your safety and not the money you would be paid for taking part in a trial.

It is important that participants at trials should be provided with necessary care and treatment for HIV/AIDS and its associated complications. It is important that participants be provided with access to health care during and after the trial

Do not forget that the decision, whether or not to participate in a trial, is entirely yours. You should allow anybody to force you to participate. Do not participate because others are participating. If you are not satisfied with the arrangement and you do not wish to participate, there is no punishment for this.
You can withdraw from the trial at anytime, if you feel like. It is advisable for you to discuss your participation with your doctor, friend, spouse or family members or your counsellor for a second opinion.

As the trial comes to an end, you may be wondering how you will take care of your HIV/AIDS status. You might not need to worry too much as members of the research team are expected to work with you and your doctor to determine the best plan for your HIV treatment. You should be informed of the result of the trial the moment it is out.


Some international rules and standard on clinical trials:

The Nuremberg Code, 1947

The Nuremberg Code identifies informed consent as an absolute pre-condition for the conduct of research involving human subjects. Its usefulness today is limited, other than to remind us of the dangers of unchecked medical experimentation.

Declaration of Helsinki, 1964 (last amended 1996)

The Declaration of Helsinki provides basic principles for the conduct of medical research on human subjects. The principles in the Declaration are reviewed and revised from time to time. In 2000, a working group prepared amendments that provided: “In any medical study, every patient – including those of a control group, if any should be assured of proven effective prophylactic, diagnostic and therapeutic methods.

Ethical Principles and Guidelines for the Protection of Human Subjects in Research (the Belmont Report), 1979

The Belmont Report was prepared by the US National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research. Because of its clarity and authority, the Belmont Report is a standard reference on ethics in research involving human subjects. The Report sets out three basic ethical principles to guide research namely: respect for persons, beneficence, and justice.

International Ethical Guidelines for Biomedical Research involving Human Subjects (the CIOMS Guidelines), 1982 (last amended 1992)

These Guidelines are published by the Council for International Organisations of Medical Sciences (CIOMS). They expanded and extended the ethical principles embodied in the Declaration of Helsinki, particularly to research in developing countries.
The CIOMS Guidelines were revised in 1992, in part to address specific concerns about HIV/AIDS research, and are again under revision. Preliminary consultation was held in March 2000. Background papers were published later in 2000.

Ethical Considerations in HIV Preventive Vaccine Research: UNAIDS uidance document 2000

In 1998, UNAIDS conducted a series of regional and international consultations to try to achieve a global consensus on key ethical issues in HIV preventive vaccine research. The UNAIDS guidance document sets out UNAIDS’ policy in 18 guidance points that address a wide range of issues, including: international response, access, capacity development, community representation, benefits, harms, consent, care and treatment.

An international code of ethics for business: The Global Compact

The Global Compact challenges individual corporations and representative business associations to support nine key principles relating to human rights, labour and the environment, ‘which emanate from universally agreed standards found in United Nations documents.’ The application of the Global Compact to the HIV vaccine research and development is yet to be explored.