Clinical Trials FAQ

The Belmont Report: Protecting People in Clinical Trials

The Belmont Report: Protecting People in Clinical Trials

Clinical trials advance cancer research and help current and future generations find new treatments for disease. However, when patients enroll in a clinical research trial, they want to know that they are safe and that the trial won’t do more harm than good. 

Doctor smiling while holding a stethoscope

Enter the Belmont Report, a set of fundamental ethical principles and guidelines that assist researchers in resolving ethical principles when conducting research involving human subjects. In this article, we look at the history and content of the Belmont Report and its implication on cancer research.

History of the Belmont Report

The Belmont Report was created due to several contributing factors that made the need for a code of ethics in medical research using human subjects essential. 

The extreme human rights violations during World War II, followed by the events of the Tuskegee study, prompted Richard Nixon to create the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This commission ultimately produced the Belmont Report.

The Nuremberg Code

Following the horrors of World War II and the information unraveled in the Nuremberg Trials, the international scientific community discovered a need for a code of ethics when conducting research on human subjects.

The Nuremberg Code, published in 1947, was created as a guide to satisfy moral, ethical, and legal concepts surrounding human experimentation. The document laid out 10 essential points for conducting ethical research. Amongst other things, the points included the following:

  • Requirement for voluntary consent
  • Qualifications for researchers conducting experiments
  • The importance of ensuring the benefits of an experiment outweigh the risks
  • Participants’ right to terminate the experiment
  • Investigators duty to terminate an experiment if they believe it will result in harm to the subjects

While the Nuremberg Code was a good start for providing ethical guidance in conducting human research, it soon became apparent that further action was needed.

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“Trials happen in early-stage disease. They can be as a first-line treatment, when someone is first diagnosed, and also with advanced disease, where the goal of the trial is how to improve the standard treatment either by adding new medication or changing medications completely based on data from studies in advanced disease.”

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Public Health Services (PHS) Tuskegee Study

From 1932 to 1972, the United States Public Health Service (PHS) conducted a study to observe the effects of syphilis if it remained untreated. During this period, the PHS observed the impacts of syphilis on nearly 400 black men. 

The main problem of the study was that the patients were not informed of the true intent. In fact, they were blatantly lied to as they were told that they would be treated for the disease in return for meals, medical exams, and burial insurance. However, throughout the study, patients were denied access to penicillin, the treatment for syphilis. 

The lack of information provided and disregard for the patients’ well-being led to a class action lawsuit and increased scrutiny of human subject protection policies. 

National Research Act (1974)

The National Research Act of 1974 was passed due to the public attention surrounding the PHS Tuskegee Study. The Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which was charged with developing a code of ethics and conduct for research involving human subjects.

While the Nuremberg Code provided the guidelines for ethical human subject research, the National Research Act codified those requirements into US law. The National Commission produced the Belmont Report in 1979, which remains one of the most important reports in protecting the safety of human subjects in medical research. 

The 3 Basic Ethical Principles

The main product of the Belmont Report was the publication of three basic ethical principles to help guide and resolve ethical problems surrounding research with human participants. The three principles are:

  • Respect for Persons: All people should be respected. This includes children and individuals who may not be capable of making informed decisions due to mental or physical disabilities.
  • Beneficence: Research should not intentionally harm humans. In addition, researchers should look to maximize the potential benefits of a study and minimize the potential risks.
  • Justice: The benefits and burdens of research should be distributed fairly.

Although the Belmont Report was published almost half a decade ago, its guiding ethical principles still remain relevant today. In the next couple of sections, we will look at how these guiding principles have been applied to the way clinical trials are managed.

“A big part of what we do is help to educate and really clarify what clinical trials are.”

Leah Szumita, Clincal Trial Support Director at The LLS| Watch “What is a Clinical Trial Really?

Applications of the Belmont Report

The three ethical principles are phenomenal foundational ideas; however, they are just that: ideas. Understanding how the idea translates to actual clinical trials is essential for research participants to feel safe agreeing to participate in trials.

Here are a few of the ways that the three principles have been applied to research:

  • Respect for Persons -> Informed Consent: Patients have the right to make the decision to participate or not to participate in a trial. To consent to participate in a trial, potential participants must receive information about the trial, be able to comprehend the impacts of a trial, and voluntarily agree to the trial. All three factors must be present to provide informed consent.
  • Beneficence -> Assessment of Risks and Benefits: Researchers need to thoroughly examine the benefits and potential risks of a study. Without clear supporting evidence that a trial will do more good than harm, the study can’t move forward. 
  • Justice -> Selection of Participants: Researchers are required to implement a fair and equitable method for selecting study participants. When possible, participants should be from a diverse set of backgrounds.

These three applications have become standard practice in conducting research. All three applications should be clearly evident in all trials.

Institutional Safeguards

Researchers can generally be trusted to have the safety and well-being of their patients in mind. However, research and academic institutions have created several fail safes to ensure that patients are well protected. 

Institutional Review Boards

The Institutional Review Board (IRB) is a group specifically formed for the purpose of ensuring that people participating in clinical trials are protected and that all federal laws are followed. Before they are formed, IRBs are approved and overseen by the Office of Human Research Protections. 

Before a clinical trial can start recruiting patients, they must receive approval from an IRB. The trial is then continuously overseen by the IRB to ensure compliance.

Data Safety Monitoring Boards

A Data Safety Monitoring Board (DSMB) is a panel of experts that are typically brought on during a phase III clinical trial. The DSMB observes the progress of a clinical trial and stops it if:

  • It becomes clear the treatment is much better or much worse than the current standard of treatment.
  • There are extreme safety concerns that make it obvious that the risks of the trial outweigh the benefits of the trial.
Clinical Investigators

While both the DSMB and IRB are not directly involved with the study, the clinical investigator, sometimes referred to as the principal investigator, is directly overseeing all aspects of a clinical trial. 

The clinical investigator is responsible for ensuring that all trial participants understand any risks involved with participating in a study and for ensuring their safety throughout the trial. 

“Never think of trials as being exposed to random things. They’re very well thought out. More often than not, you have a high level of reassurance.”

Dr. Rafael Fonseca | The Latest on Multiple Myeloma

Are Clinical Trials Safe?

As a result of the Belmont Report and the resulting events that followed, clinical trials have become much safer for participants. Doctors are required to inform patients of all the potential risks of enrolling in a clinical trial and ensure that the potential benefit of the trial outweighs the risks. 

While it’s impossible to guarantee that a trial will be completely safe, patients can be assured that they’ll have all the information they’ll need to make the decision that is right for them. 

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Dr. Joseph Mikhael discusses exciting advances in multiple myeloma screening, including new information from the iSTOP and PROMISE clinical trials.

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Focus: Multiple myeloma, Waldenström’s Macroglobulinemia, early screening, clinical trials
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American Cancer Society. Protecting People in Clinical Trials. Accessed at on October 15, 2023

Columbia University. Ethics and the IRB. Accessed at,a%20rich%20history%20of%20development.&text=“Good%20judgment%20comes%20from%20experience,experience%20comes%20from%20poor%20judgment.”&text=The%20Institutional%20Review%20Board%20(IRB,for%20research%20with%20human%20subjects on October 15, 2023.

HHS. The Belmont Report. Accessed at on October 15, 2023

University of North Carolina. Nuremberg Code. Accessed at on October 15, 2023

ERAU. History of Ethics. Accessed at on October 15, 2023

FDA. Institutional Review Board Frequently Asked Questions. Accessed on October 15, 2023.

Multiple Myeloma Specialist Rafael Fonseca

Multiple Myeloma Screening | Rafael Fonseca, MD

Multiple Myeloma Screening

Rafael Fonseca, MD
(ASH 2021)

Published March 2022

This image has an empty alt attribute; its file name is Rafael-Fonseca-SQ-1024x1024.png

Dr. Rafael Fonseca shares information about multiple myeloma clinical trials, new therapies, and emerging changes in the standard of care for multiple myeloma patients, following the American Society of Hematology (ASH) 2021 conference,

Dr. Fonseca has been a practicing hematologist for almost three decades, now interim executive director at Mayo Clinic. As a veteran specialist of the myeloma field, he shares his insights on the latest in emerging treatments and clinical trial studies.

The interview has been edited only for clarity.

Studies: iSTOP and PROMISE

The Patient Story: There were two big studies discussed at ASH focused on screening: iSTOP in Iceland, and the PROMISE study led by Dana Farber that started a couple of years ago, which focused on diverse populations. Can you describe the importance of those studies?

Why iSTOP Matters

This [iSTOP] is an incredibly important trial. Their goal was to do the whole screening for the country of Iceland. And what they went about to do was set up a system whereas people would be offered to be screened for the presence of monoclonal proteins. And they have a very robust partnership with the laboratory methodology to be able to test this at a high level and with great precision.

This is where phase III trials meet real world data, and really establishes some very interesting findings.

Dr. Rafael Fonseca

They went about to do a population based study, and at the end of it all, it was very, very large– 75,000 people. This is where phase III trials meet real world data, and really establishes some very interesting findings.

There were three or four key takeaways. One is that we know there’s a small fraction of the population with smoldering multiple myeloma, so they have established that through screening. It’s less than one percent that they estimated, but it’s still measurable. And that is important because as we have clinical trials where people are saying we should think about treating smoldering, we’re going to have to be more and more careful about that.

One of the randomizations was how to approach patients and then what to do afterwards.  What they’re trying to see is if you have an early intervention, and you detect this early, then you can prevent some of the complications.

That’s very important because a myeloma patient who progresses to development of lytic bone lesions, especially if that results in a fracture, or renal problems, can have lifelong consequences. Then, as they live many years now after diagnosis, that’s very undesirable.

It also establishes the baseline for the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in that population. So what we need to do is to think about how this extrapolates. I think there’s a susceptibility according to the various regions, but for what they tried to test, it was a remarkable study.

Why PROMISE Matters

PROMISE is a very large study led by the team of Dr. Ghobrial from Dana-Farber. And they’re able to show higher prevalence than expected for monoclonal gammopathy.  In populations at risk, although the numbers will evolve, the number I keep in my head is about 10%. That’s in people who have family members who have monoclonal gammopathy or individuals of African-American ancestry, who have a higher incidence for this.

I hold the belief that many of us have slightly abnormal plasma cells somewhere in our body because we get exposed so many times through our lifetime that the opportunity for a mistake is actually quite high.

Dr. Rafael Fonseca

The other finding that was remarkable was that they found that a small fraction of patients that have abnormalities that would be a little bit more like a pre-MGUS, and some of those were reported as transient.

Now, there’s no reason to believe that humans don’t have some old clones. We know that for other tumors. So it was only logical that in time it would be found in patients who have things like MGUS. I hold the belief that many of us have slightly abnormal plasma cells somewhere in our body because we get exposed so many times through our lifetime that the opportunity for a mistake is actually quite high.

But you know, the studies are descriptive for the most part right now. But I really commend the efforts of the team of Dr. Ghobrial as well, too, in trying to establish this new baseline.

Takeaways for Current Patients

The Patient Story: What are the takeaways for current patients regarding screening?

You know, there is no agreement at the moment regarding screening strategies or recommendations. And the reason for that is that these are conditions for which we don’t necessarily have treatments that will completely eradicate the process.

You screen for polyps because if you can excise those polyps, then you decrease the risk of colon cancer. But with the bone marrow, it’s very hard to do that because you can’t go in and just pull out the abnormal cells and then leave the rest of the bone marrow.

There is no question that, as time goes by and as the cells grow, there’s a greater likelihood that one might have a complication.

Dr. Rafael Fonseca

However, the question will change as was shown by the iSTOP study, because now the question is, “Can you do something to prevent a complication from happening?” There is no question that, as time goes by and as the cells grow, there’s a greater likelihood that one might have a complication.

So if you detect early, you might not be able to move on fully to the curative approach, although there are some clinical trials that are asking that question. But you might be able to establish a more careful monitoring strategy so that the next time you meet that person, it is for another laboratory testing, and not because the person has been admitted to the hospital with a fracture or with renal failure.

I think with most of the patients we see that have this condition, there’s somewhat surprise findings. You know, they’re going for a physical, and they’re found to have an elevated protein or someone orders a protein electrophoresis for other reasons, and now they know they have it. So we monitor them, but we don’t do this at large.

Genetic Screening

Now we get the question often from family members. “My mom or my dad has myeloma. What can I do to test?” So we give them the names of those tests, but without much information as far as what to do. And I feel like patients and families should know as well that we don’t have the best pathways yet defined, as it’s still early on.

[Testing] is a double-edged sword, because now you know you have it, then that creates a little bit of stress and anxiety. But on the other hand, you can prevent those complications.

Dr. Rafael Fonseca

But for instance, if you were in a family where there’s two or three members who have myeloma, that would be a pretty strong signal that there’s some familial clustering and then the person might want to test. And why not, if they find something to monitor? It’s a double-edged sword, because now you know you have it, then that creates a little bit of stress and anxiety. But on the other hand, you can prevent those complications.

Interestingly, at this meeting, we had a presentation by a team that looked for germline genetic changes that may predispose people to myeloma. They found that about 9% of patients have some genes that potentially could be contributing to the development of myeloma. Again, it’s very early, but that would be another path to explore as well.

Identifying Risk for Black Patients

The Patient Story: With PROMISE, there was a focus on Black patients, and a recognition that the high risk population over 50 years old was twice as likely as the general population to have MGUS. If you are a Black patient, what do you need to know about elevated risk, and do you need to talk to your primary care doctor? 

You know, it could be right, but I don’t think we are ready yet to make recommendations. I think for readers in the audience who may have this question or that concern, it’s a fair request that your doctor does that testing if you are interested. As I mentioned earlier, we don’t have guidelines. I can’t pull them out and say, “This is what needs to be done.”

But I think people rightfully are concerned and would like to know. And the obvious question is, “Why?” And the “why” is so that you can have a good screening strategy. I hope that within the next five to ten years, we will have more specific guidance as far as what to do because again, if we can prevent complications, that would be pretty good.

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