Ethics In Clinical Trials: Regulations And Ethical Concerns

Clinical research is a vital component in the healthcare landscape, enabling new cures, treatments and medications to be uncovered and brought to the wider population. To ensure complete accuracy and transparency, the clinical research process is also committed to ethical standards.

Here, we’ll take a deeper dive into ethics in clinical trials, including their importance, concerns, and how to ensure clinical trials are conducted ethically.

What are clinical trials?

Clinical trials are research studies designed to evaluate the safety and effectiveness of new treatments, drugs, or alternative therapies. They are conducted with human participants and are essential for developing new medications, devices, vaccines, or treatment protocols.

To ensure the highest levels of credibility, reliability, and ethically sound results in clinical trials, an emphasis is placed on ethical oversight, participant safety, and scientific integrity.

The goals of clinical trials and clinical research

Clinical trials aim to answer a research question or hypothesis, as agreed in the research planning stage. There are several different types of questions and hypotheses that a clinical trial may seek the answer to, with some of the common overarching goals including:

• Treatment research - in this case, the study looks at new medications, psychotherapy approaches, intervention innovations, medical devices, and surgical or therapeutic techniques.
• Prevention research - this goal seeks to stop the development or recurrence of a disease or condition using elements including medication, vitamins, vaccines, and lifestyle changes.
• Diagnostic research - researchers often use clinical research to establish new ways of identifying conditions so that medical professionals can become more aware of tell-tale signs in patients.
• Genetic studies - researchers can improve disease prediction by researching the link between genes and disease. This helps medical professionals estimate the chances of an individual contracting a disease or condition.
• Epidemiological studies - some populations are more likely to contract certain conditions. Epidemiological studies can be used to spot patterns, causes, and methods for controlling conditions and diseases in certain groups.

There are also several different types of clinical trials, with differing goals and timescales. The key thing to remember is that every clinical trial is different and any information provided about the trial should discuss everything a participant needs to know.

Phases of clinical trials

To ensure the safety and efficacy of clinical research, most clinical trials comprise several stages. Each stage of a clinical trial has a different purpose, with the shared outcome of ensuring the research is comprehensive, effective, and beneficial.

The typical phases of a clinical trial include:

• Phase 1 - safety testing
• Phase 2 - efficacy and side effects
• Phase 3 - comparing with current treatment
• Phase 4 - post-market surveillance

Importance of ethics in clinical trials

The importance of ethics and clinical research cannot be understated, and ethics is important for several reasons. Firstly, designing and conducting a clinical trial ethically ensures the integrity of the research results. This means the data obtained is more trustworthy. Secondly, ethical studies protect the safety of participants by making sure they are not exploited or treated unfairly at any point during the trial.

Federal regulations require any research projects involving human participants to be approved by an Institutional Review Board (IRB). This ensures the trials are ethical and all participant rights are protected.

Several core principles in clinical research guide the work of medical teams and researchers, which we’ll go into detail about later on. Some examples include:

• Verifying the scientific validity of trial results
• Carrying out scrupulous and fully compliant testing with stated clinical protocols
• Fairly selecting trial participants without prejudice or bias
• Ensuring participants are fully informed about the trial before they offer consent, including any potential risks

Clinical researchers also follow ethical frameworks for moral guidance when designing and conducting clinical trials.

Ethical concerns within clinical trials

While clinical trials offer many important benefits to participants, medical research, and the wider population, there is still concern when it comes to ethics.

Deception of participants

Historically, there have been several occasions in medical research where subjects were involved in a trial either unknowingly or deceived into doing so. A couple of examples of this include the Tuskegee Syphilis Study and the Nazi experiments undertaken during World War II. The latter example involved subjects consenting to clinical research under duress and deception.

Clinical research has come a long way since this time, and these historical missteps have paved the way for the development of more stringent ethical guidelines and regulations. This includes the Declaration of Helsinki and the Belmont Report.

Use of placebo

Many clinical trials use a placebo in place of a potentially beneficial treatment for some groups involved in the study. This has become an ethical concern, particularly in trials researching treatments for serious or life-threatening conditions. This is because withholding active treatments could have significant implications for those with the condition.

As such, researchers must carefully consider when placebos can and should be used in a clinical trial. To use them effectively, researchers must determine that a placebo is ethically justifiable on a case-by-case basis.

Balancing patient protection and autonomy

In some clinical trials, an ethical dilemma between participant protection from risks and autonomy could arise. Medical research teams need to protect potential subjects from making imprudent decisions, while also respecting their right to autonomy - which is a key pillar in clinical research. There are several ongoing debates about the level of protection versus potential paternalism in clinical research.

Research involving vulnerable populations

Depending on the research project, some clinical trials will have ethical concerns surrounding the participant group. It is widely accepted that special considerations should be taken for vulnerable populations including pregnant women, children, and those with incurable diseases. When pregnant women are involved in a trial, medical researchers should carefully weigh up the risks and benefits to ensure any potential fetal harm is erased or minimized.

For children, consent must be given by the parent or guardian, with assent from the child when possible. People with incurable diseases may have unrealistic expectations of the trial, born out of hope or desperation, so their selection and expectations should be carefully managed. Additionally, developing countries could have financially motivated participants which could lead to both ethical and biased issues.

Monetary compensation

Occasionally, financial incentives can be used in clinical trials. This can be particularly problematic in developing countries. These incentives could be significantly relative, or more than a participant’s usual income, thus potentially resulting in concerns around coercion.

When considering ethics in a clinical trial, researchers must ensure that financial compensation does not directly influence the decision to participate, while also ensuring participants completely understand the risks involved in the trial.

How to conduct an ethical clinical trial

We’ve already discussed some of the elements involved in ensuring a clinical trial is ethical in both design and participation. When considering how to conduct an ethical clinical trial, medical researchers need to make sure they follow core principles and ethical frameworks.

Ethical codes

Several ethical codes and frameworks are currently in place across the world to ensure compliance and ethics in clinical trials:

• The Nuremberg Code - Introduced shortly after World War II, following abusive clinical trials undertaken by Nazi scientists, the Nuremberg Code provides an international standard for ethics in clinical research.
• The Belmont Report - This document was created by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It identifies basic ethical principles and guidelines that address ethical issues that could arise when carrying out research with human participants.
• The Declaration of Helsinki - Put forward by the World Medical Association, this international agreement continues to be amended over the years to address new ethical concerns as they arise.
• The U.S. Common Rule - Underscoring biomedical research in the US, this legislation requires researchers to ensure participants give informed consent when partaking in a clinical trial.

Ethical principles for conducting clinical trials

To guide the conduct of clinical research, many researchers will use a set of core principles to ensure the trial is ethical. Before a clinical trial can begin, the research teams must consider how these core principles can be managed throughout the trial.

Social and clinical value

The first principle for consideration is social and clinical value. With this, researchers must ensure the trial has the potential to generate valuable knowledge that could benefit society or improve clinical practice.

When planning a clinical trial, researchers must ensure the question being answered will contribute to the wider scientific understanding of health. It should also improve the ways medical professionals prevent, treat, and care for people with specific conditions.

A key element of this principle is ensuring society will gain useful knowledge from the results of the trial. It is thought that exposing human participants to the risk and burden of research in the name of science is only justifiable if society benefits.

Scientific validity

Clinical trials should be designed in such a way that ensures the data obtained answers a valuable research question. The study design should be valid, methodical, rigorous, and have a clear scientific objective to ensure validity.

Fair subject selection

Once the scientific goals of a clinical trial have been agreed, they should be used as the primary basis for the recruitment and enrollment of participants. As such, vulnerability, privilege, and other factors unrelated to the goal of the study should not be considered as this would make the trial unethical.

For fair subject selection to occur, recruitment should be in line with the scientific purpose. Those chosen should also be selected in a way that minimizes risk while enhancing the benefits of the trial.

Favorable risk-benefit ratio

Many of the core principles in ensuring clinical trials are ethical surround the participant, and the risk-benefit ratio is no different. Clinical researchers must ensure the potential benefits of the research outweigh the participant risks.

Independent review

All clinical trials should be designed to minimize any potential conflicts of interest, ensuring they are ethically acceptable before starting. To do this, independent review panels with no vested interest in the study should be asked to review the study proposal. As part of this review, the panel should ask important questions to gain a full understanding of the trial, including whether those conducting the study are sufficiently free of any bias.

In the United States, these reviews are carried out by granting agencies, local institutional review boards (IRBs), and data and safety monitoring boards.

Informed consent

We’ve already mentioned informed consent, but it’s a vital principle in clinical trial ethics. Participants should be fully informed on the nature, purpose, risks, and benefits of the trial before they consent. When they do give their consent, this should be voluntarily and completed without coercion or undue influence.

For a clinical trial to be ethically sound, participants should be free to make their own decisions regarding their initial participation and ongoing involvement in the research.

Respect for potential and enrolled subjects

Participant protection and respect are key in creating an ethical study. Researchers should ensure participants’ privacy is respected and their private information is kept confidential. This also includes respecting the right of a participant to change their mind or determine that the study no longer meets their interests. They should be free to leave a study at any time, without penalty or consequence.

Respect in a clinical trial also extends to information. Researchers should inform participants of any new information throughout the trial as it arises, and be respectful of the fact that this information could influence a participant’s decision to continue with it.

Medical teams should also monitor the welfare of participants, checking for adverse reactions and changes. Collecting this information regularly means researchers should also ensure participants receive the appropriate treatment, and if necessary, be removed from the trial for their safety.

Respect for participants doesn’t stop at the end of the trial. After the trial, researchers should inform participants of the results of the trial, and check on their welfare.

Impact of unethical practices on clinical research

There have been many historical instances of unethical practices in clinical research, and this has had a profound impact on many areas in the clinical research landscape. Some of the impacts that unethical practices have had include:

• Participant wellbeing - Clearly, the key worry with unethical practices in clinical research is the possibility of causing harm to participants. If a medical research team violates consent, breaches safety protocols, or provides misleading information, this could lead to serious implications for the wellbeing of participants.
• Negative public perception - Unethical practices have and can lead to a loss of public trust in medical research. The impact of this is that future studies could see a reduction in participant sign-ups, resulting in the hindrance of developments in new treatments and medical knowledge.
• Professional reputation - For medical researchers, unethical practices could mean they experience long-term reputational damage. In turn, this could lead to them being unable to collaborate or secure funding for future research projects.

Examples of unethical behaviors in clinical research

Unfortunately, over time, there have been several instances of unethical practices in clinical research. However, these occasions have since highlighted the importance of ensuring ethical standards are considered and maintained in clinical trials. Here are some key examples of ethical issues in clinical research.

Plutonium Trials

During World War II, medical researchers in the US sought a greater understanding of the effects of plutonium on the human body. As part of the Manhattan Project, these government researchers injected 18 hospital patients with radioactive plutonium. The problem is that documentation from that time suggests the participants were not fully informed of the potential risks. Additionally, the participant selection process is unclear.

Many patients received a dose of plutonium that exceeded existing guidelines, which resulted in them suffering long-term health conditions. The subjects also only lived for an average of 11.7 years after injection. The unethical nature of the plutonium trials caused the government to reform clinical research policies, including emphasizing informed consent.

Tuskegee Syphilis Study

Perhaps one of the most famous clinical trials in terms of unethical behaviors, the Tuskegee Syphilis Study in 1932 sought to understand syphilis transmission. The Tuskegee Institute recruited 600 black men to participate in the trial but misled the men about the nature of the treatments they were receiving. They did not give them all the information about the trial, including its real purpose. This means they gave consent under deceptive circumstances.

The unethical nature of this study was made public in 1972, to much public outcry. By this date, 28 participants had died from syphilis and 100 more had passed from complications related to the injections. In addition to the men involved in the trial, at least 40 spouses had contracted syphilis, and 19 children had it passed onto them at birth.

Ethical concerns in ongoing research studies

Although clinical research has come a long way, and ethics plays a large role in study design, it’s still possible to experience ethical concerns in modern clinical trials. While advancements have been made to ensure ethics are considered, it’s still important to maintain vigilance and integrity in clinical research.

COVID-19 vaccine trials

While COVID-19 is no longer a major threat, conversations are still being had about the ethics surrounding the urgency of finding a vaccine. Questions have been raised on how to conduct trials expediently, but also in a fair, safe, and clinically sound manner.

Many of the questions raised surround public consultation and independent reviews, with many believing the public should be engaged before, during, and after the trials to ensure they are ethically sound. Likewise, many people are considering how quickly and easily experts can conduct an independent review of the results to establish whether the vaccine or treatment benefits outweigh the risks.

Stem cell research

Stem cells have a unique ability to maintain, replenish and repair all types of tissue, and have played a key role in life-saving treatments. However, stem cell research is particularly controversial due to the nature of how stem cells are harvested. Those against stem cell research argue that it’s unethical because stem cells are derived and destroy an implanted human embryo from its sixth to the eighth day of development.

Human gene editing

Genetic engineering has been around for some time, with many arguments surfacing on the ethics of doing so. In 2018, Chinese researchers used CRISPR to change the genome of twin embryos to prevent an HIV infection. This caused great dismay and confusion in the research community, with the key researcher spending three years in prison for “illegal medical practices”.

Since the scandal, China has made improvements to its regulation of human genome editing, but concerns are still raised on whether human genome editing should be allowed at all.

Summary

Ethics plays a big role in the design and implementation of clinical trials and will continue to be a key consideration for the medical research community. Likewise, ethical concerns will remain prevalent and research teams will be required to deeply consider ethics when planning a clinical study.

Whether you’re interested in joining a clinical trial soon or you’re simply educating yourself on the ins and outs of clinical research, understanding clinical trial ethics is highly important.

FAQs

Is it more ethical to experiment on humans than on animals?

Ethics is not a black and white topic and ethical considerations can differ greatly. While human trials are conducted with consent and participated in voluntarily, animal trials are concerned with minimizing suffering and adhering to ethical standards for animal welfare. In addition, human trials are only conducted after sufficient animal testing has been completed and safety and efficacy have been indicated.

What are the responsibilities of a clinical trial researcher?

A clinical trial researcher has many responsibilities, including ensuring the trial is conducted ethically. Some of the key responsibilities of a clinical researcher include:

• Ensuring participant safety and wellbeing, both at the start of the trial and throughout
• Carrying out the trial as per the approved protocol and agreed ethical guidelines
• Obtaining informed consent
• Maintaining participant confidentiality and data privacy
• Reporting accurate results
• Monitoring participants for adverse reactions or side effects
• Addressing side effects

What is the role of an Ethics Committee in clinical trials?

In clinical trials, Ethics Committees are responsible for the scientific and ethical review of research proposals. They will review and approve proposals to ensure ethical standards are met, while also ensuring the rights and safety of participants are protected. An Ethics Committee may also ensure informed consent has been given, monitor the trial for ethical compliance and safety, and advise on any ethical dilemmas as they occur.