What is Informed Consent for Research Subjects?

informed_consentAs I mentioned in my last post, the Institutional Review Board (or IRB) has a responsibility to review and monitor all human subject research to help ensure that the subjects are treated ethically.  But how does the patient know what they are getting into if they are interested in participating in  a research study?

One of the key parts of the Belmont Report (that report that sets the rule for human subject research) says that subjects must be treated with respect.  A huge part of this is to inform research subjects about the research, the risks, and the possible benefits. Because of the importance of informing the subject, most research studies involve providing the potential participant with an Informed Consent Form (ICF) that the they must read, understand, and sign before joining a clinical trial.  This informed consent form is reviewed by the IRB and usually much discussion goes into whether it is clear (ideally 6th-8th grade reading level), accurate, and informative.

So how do investigators or the IRB know what to inform the potential participant about in this informed consent? Well the government tells us – of course! The intuitively named Title 45 CFR 46 subparts A, B, C and D outline the rules and regulations for human subjects research.  Because this is the government’s stupid way of naming things, the easier name used for these rules is the Common Rule. This rule outlines what’s needed in an informed consent form (paraphrased directly from the Common Rule):

  1. A statement that the study involves research, an explanation of the purposes of the research and the expected length of the subject’s participation, a description of the procedures to be followed, and identification of any procedures which are experimental.
  2. A description of any reasonably foreseeable risks or discomforts.
  3. A description of any benefits to the subject or to others which may reasonably be expected from the research.
  4. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might benefit the subject.
  5. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records.
  6. For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained.
  7. An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury to the subject.
  8. A statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

The intent of the informed consent is for the subject to actually be informed.  This means that the investigator needs to clearly and honestly explain the research to the subject.  For example, when we provide informed consent for patients to provide tissue samples for the biobank, we tell them that their tissue may be used for any type of future research, it may be used to create commercial products but won’t financially benefit them, and that we won’t be able to provide any research results back to them.  In this context, participating in the biobank may sound like a raw deal.  However, we also explain how the tissue they donate will be used by researchers to better understand diseases and develop new treatment. Therefore, even though they may not directly receive benefit, they may benefit others with their disease in the future.

The potential participant is also given the chance to ask all the questions that they have about the study.  They can ask to bring the consent home to read it.  They can ask their doctor about it. Then after they are fully informed, they decide if they want to sign it or not. If not, that is okay.  It’s up to the patient if they want to participate and the investigator cannot do anything to coerce the patient to sign or participate.  At the same time, if the patient does decide to participate, they may leave the research study at any time with no penalties. Their participation is entirely voluntary.

One other quick note about making sure the patients are fully informed…the Common Rule has added additional safeguards in the case “when some or all of the subjects are likely to be vulnerable to coercion or undue influence.” These vulnerable subjects include children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons. For example, you don’t want to force imprisoned people to participate in research just because they are in jail or poor people to participate just because you are paying them a lot of money to participate.

The US Office of Human Research Protection is working on changes to the Common Rule right now (it’s called a Notice of Proposed Rulemaking – these silly government names).  The original re-write was sent out to the public for review in 2011.  The updated version was made available in September of this year (look at that for the glacial swiftness of the government!) for even more review.  It has many proposed changes that will affect human subject research and research using human tissue samples. To learn more about what this means for clinical and other research, check out the recent story from NPR.

Overall, the purpose of informed consent is to make sure anyone volunteering to participate in a research study knows what they are getting into. If you are interested in a clinical research study, can you find more at clinicaltrials.gov or talk to you physician.

Institutional Review Board (IRB) – Keeping Research Subjects Safe


I was working over the holiday weekend, but at least I was working in my decorated living room with a fire going (the high in Arizona was only 66 today!!)

Hope you had a fabulous Thanksgiving weekend! Four day weekends are great, and even I took some time off to enjoy the holiday with my husband and the puppies.  And then I got back to work because I have an Institutional Review Board (shortened usually to the acronym IRB) meeting in two weeks and the committee has eight new protocols to review. This likely means very little to you, but the IRB is what ensures that the rights and welfare of humans participating as subjects in a research study are adequately protected. And here’s why that’s important…

In a previous post, I explained clinical research.  Clinical research studies new drugs or devices to determine if they are safe or effective. As you can imagine, at a world-class hospital, we have hundreds of clinical trials. You can check out information about these clinical trials by following the links for the Barrow Neurological Institute, St Joseph’s Hospital and Medical Center and the University of Arizona Cancer Center at Dignity Health.  Physicians and surgeons are studying new treatments for many different cancers, devices like the NovoTFF for glioblastoma, and comparing new drugs or combinations of drugs to current treatments to see if the new regime works better.

Now if a  company wants to test a new drug, they can’t just pick up the phone and ask their physician buddy if they could just use a few of their patients to test some stuff out. But why not?  Honestly, it’s because at one point researchers did some pretty crappy things in the name of science.  Thins like Nazis studying prisoners against their will and in the US and scientists who studied the untreated progression of syphilis in black patients in Tuskegee, Alabama from the 1930s-1970s. In these and other cases, the welfare of the patient (who is called a subject once they are part of a research study) wasn’t considered AT ALL and what the subjects had to endure was truly awful.

To avoid this from happening in the future, in 1974 the government passed the National Research Act, which resulted in the Belmont Report. From this, three ethical principles were developed in the treatment of research subjects:

  • Respect for persons.  This respect includes allowing them to make their own informed decisions about participating in the research.  This also means that the researcher conducting the study needs to be honest and not try to deceive or coerce patients into participating in the study. For example, the researcher can’t tell the patient that the research will be painless and cure their disease if they know it won’t.
  • Beneficence: Basically this ensures that the researchers do no harm to the research participants – for example, like the harm done during WWII or in untreated syphilis patients.
  • Justice:This is to avoid taking advantage of the patient or a vulnerable patient population.  For example, there are special rules to prevent taking advantage of prisoners or children. This principle also tries to make sure that all research participants receive benefit equally.

protocol for IRB reviewThese ethical principles have been developed into processes that are regulated by the Food and Drug Administration (FDA) and Department of Health and Human Services (specifically Office for Human Research Protections). How does the government make sure these regulations are followed?  Any institution that is performing human subject research has to obtain a Federalwide Assurance, which essentially registers the hospital or university with the government and assures the government that the hospital will follow the ethical rules and guidelines to conduct this research.

For each project or clinical trial involving human subjects, the investigator needs to put together a proposal – what we call a protocol.  This protocol includes information about exactly what is going to be done to the subjects, what the risks are, what the alternatives are for treatment, and how the subject’s safety and confidentiality will be safeguarded. This protocol is the sent to the IRB along with LOTS of other documents about how the patient will be informed about the research (in Informed Consent Form), whether or not the investigators have been trained to perform the research, and information about the drug or device being used.

The IRB is responsible at individual institutions for making sure that patients who become subjects in human subjects research are treated with respect, beneficence and justice while also decreasing the potential risks and letting the patient know what these risks are. The IRB reviews each new protocol (which is exactly what I am doing this weekend!) and at the IRB meeting (which is once a month from 7-9AM), the investigators present their protocol.  The IRB members then ask questions to the investigator and discuss the research after the investigators leave the room.  What do we discuss? It’s confidential for individual studies, but we may talk about how the study is being performed and identify possible problems with the study. We may also talk about the informed consent (what the patient reads to learn about the study – more on that in the next post) and if it accurately explains the research and the risks. We then can vote to approve the study, to send the protocol back to the investigator to answer questions or modify the protocol or to reject the study.

After the study has been approved, the IRB is also responsible for monitoring active research projects.  For example, we receive annual reports that let us know how many people have decided to participate in the study. We also monitor “adverse events.” Adverse events (or AEs) are any event that isn’t anticipated.  This can be anything from nausea to a broken leg to a rash to a missed appointment to death (death is considered a serious adverse event). Whenever an AE happens, the IRB is informed so that if it seems like there are too many of one type of AE, we can take measures to avoid them or tell the subject about an additional risk or shut the research project down.

My participation on the IRB is a responsibility I take seriously because I want any patient who comes to the facilities I work at to understand the research that may be made available to them.  And this understanding includes knowing what the research is all about and what risks the research entails. This is why I’m spending my holiday weekend reviewing research protocols for the IRB.