Lab professional pouring solvent into a test tube. Image by crizzystudio via Adobe Stock.
Aria Trivedi is a biology major with a minor in biotechnology, and she is a 2024-25 health care ethics intern at the Markkula Center for Applied Ethics at Santa Clara University. Views are her own.
Clinical trials are at the forefront of medicine and allow for new lifesaving treatments to be discovered. Clinical trials provide an opportunity for the safety and efficacy of a treatment to be examined before allowing for society's use. Even though clinical trials are essential to advancing scientific knowledge, they need to be conducted ethically. Unfortunately, this is not always the case as seen with ethical misconduct found in a clinical trial with Kaiser of Northern California.
Consent for Clinical Trials
Informed consent is communication between a patient and provider in which the patient is given information about and understands their condition, their treatment options, and the risks and benefits of the treatments while coming to an agreement on their treatment (e.g. cancer). Informed consent for clinical trials includes a basic description of the study, risks, benefits, other treatment options if available, compensation for more than minimal risk, and confidentiality. Another essential part is an explanation of participants' rights. This includes contact information and informs the patient that they are able to leave the trial at any time for any reason. With this, it is also important for the patient to know that while they can leave, it may be important to taper off depending on the treatment.
With informed consent, it is crucial for the researcher to explain all the necessary information, but also for the patients to have time to better understand the information and ask questions. Additionally, it is the responsibility of the researchers to make sure information is provided in an understandable language to the participant and medical jargon is avoided.
Ethical Issues with Clinical Trials
To address potential ethical issues, the Belmont Report was created in 1979 in which it summarized the basic ethical principles discussed by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The report outlines ethical principles of respect for persons, beneficence, and justice. Respect for persons is seen through treating patients as autonomous agents and that individuals with diminished autonomy, such as those with a mental disability, are entitled to protection. It is important for participants to enter research voluntarily and with adequate information.
Beneficence consists of two parts. First is to do no harm, which many may be familiar with from the Hippocratic oath. The second is to maximize possible benefits and minimize possible harms to the participant and society. Lastly, justice is exemplified through each person having an equal share according to their individual need, effort, social contribution, and merit.
There are federal guidelines along with institutional guidelines that need to be followed when conducting clinical trials. Institutional review boards, also known as IRBs, are meant to protect human research participants and have the ability to approve, advise modification, or deny research along with continually monitoring studies.
Kaiser Case Study
While many may be aware of ethical misconduct in trials such as the Tuskegee syphilis study or Nuremberg trials, ethical misconduct in medical research and clinical trials is still ongoing today and may be closer to you than you expect. According to the Mercury News, two highly regarded doctors and the leaders of Kaiser Permanente of Northern California’s clinical trials division are currently facing disciplinary actions following ethical misconduct in a clinical trial.
The now-halted trial looked to examine whether Vascepa, a fish-oil derived drug, could reduce complications from respiratory illness. An audit found that researchers attempted to recruit ineligible participants and continually recruited potential participants after they declined to participate in the trial.
In addition to halting the study, the FDA concluded there was fault with Kaiser's IRB in that it did not have enough authority in requiring doctors to provide necessary information when requested, in addition to Kaiser leadership inhibiting the IRB. Additionally, the FDA found that Kaiser's research institute lacks a comprehensive human research protection program which would assist in monitoring the whole research process for participants. These findings explain why some of the ethical misconduct in the trial went undetected and hint at a larger issue in Kaiser as it shows multiple ethical breakdowns.
When patients filed complaints, the IRB was not informed. Additionally, when the IRB asked for information, the researchers didn’t provide it, citing privacy and confidentiality, though this is in direct violation of the IRB policies.
One participant was re-approached by one of the researchers after declining to join the study due to being deathly allergic to shellfish. The researcher explained that the treatment would be beneficial, which is not ethically acceptable, in addition to disregarding the patient's allergy risk, which another doctor warned could be fatal.
After taking the medication, he had an unfavorable reaction and was dropped from the trial. This case shows a violation of beneficence as it is breaching the principle of do no harm. Here, the researchers are putting the participant in direct harm and not minimizing the risk to the patient, as noted by another doctor.
An audit found that 17 participants were also allergic to shellfish and should have been excluded from the study at the start. Other participants who should have not been enrolled included those with other medical problems such as cancer and those in vulnerable populations such as those with cognitive impairments. Additionally, dozens of other participants were unduly influenced as they were told the drug was beneficial, in addition to many being re-approached after stating their hesitation in participating in the trial. Multiple instances of re-approaching participants after they declined to join the trial are noted and concerning.
This case shows a lack of respect for persons as if they do not respect the decision of autonomous individuals to not participate in the trial. Staff also minimized potential side effects of the drug. This is also a violation of respect for persons as it does not provide all the information for a participant to make an autonomous choice about participating in the trial. Additionally, informed consent may be compromised here as the patient is not provided with the full risks of the treatment.
Over a dozen participants had issues swallowing and wanted to stop the study, though were told to open the capsules and take the medication, which is an unauthorized change to the FDA-approved protocol. The IRB also found issues with documentation, data management, administrative and procedural practices, and protocol adherence. The audit was confirmed by the researchers though they note the study was misrepresented in certain instances. The researchers' appeal to continue the study was denied.
While the study was terminated as listed on the federal clinical trials website, both doctors are still listed on Kaiser’s website, though it is unclear whether they are still conducting research. IRBs are meant to ensure that studies and researchers follow ethical and federal guidelines. IRBs ensure that informed consent is given, no trial promises safety or efficacy, participants at an additional risk are excluded, and that participation is voluntary. Multiple ethical breakdowns are seen in this situation which allowed for problems to occur and go undetected. First, the IRB was not given the proper authority by Kaiser's leadership. This hints at a bigger cultural issue in Kasier’s leadership in their priorities of research ethics and the IRB. Additionally, as the FDA found, Kaiser does not have a comprehensive human research protection program, which would have provided more protection to participants and potential participants. Accreditations such as the Association for the Accreditation of Human Research Protection Programs, provide a high quality accreditation and education model for institutions conducting research with human participants.
This case shows the importance of ethics in clinical trials and the multitude of ways ethical principles can be violated. While many researchers conduct clinical trials ethically, this case goes to show that ethical misconduct is still seen today and in your neighborhood.
Going Forward - Recommendations for Participants
- Know your right to withdrawal participation in trial at anytime for any reason
- If something happens or you feel that ethical misconduct is occuring, make sure to report it to the proper organization or person, such as the study coordinator or FDA
- If you feel pressured by researchers, take your time, ask questions, and report the researchers if necessary to the proper organization or person, such as the IRB
- Take your time before signing consent forms and make sure you fully understand them. Don't be afraid to ask questions
- Keep a copy of the consent form and ask for one if not provided