Protecting Clinical Study Subjects

By John Pezzullo

After you’ve designed your study and have described it in the protocol document, it’s time to set things in motion. In any research involving human subjects, two issues are of utmost importance:

  • Safety: Minimizing the risk of physical harm to the subjects from the product being tested and from the procedures involved in the study

  • Privacy/confidentiality: Ensuring that data collected during the study is not made public in a way that identifies a specific subject without the subject’s consent

Regulatory agencies

In the United States, several government organizations oversee human subjects’ protection:

  • Commercial pharmaceutical research is governed by the Food and Drug Administration (FDA).

  • Most academic biological research is sponsored by the National Institutes of Health (NIH) and is governed by the Office for Human Research Protections (OHRP).

Other countries have similar agencies. There’s also an organization — the International Conference on Harmonization (ICH) — that works to establish a set of consistent standards that can be applied worldwide. The FDA and NIH have adopted many ICH standards (with some modifications).

Working with Institutional Review Boards

For all but the very simplest research involving human subjects, you need the approval of an IRB — an Institutional (or Independent) Review Board — before enrolling any subjects into your study. You have to submit an application along with the protocol and an ICF (see the next section) to an IRB with jurisdiction over your research.

Most medical centers and academic institutions — and some pharmaceutical companies — have their own “internal” IRBs with jurisdiction over research conducted at their institution. If you’re not affiliated with one of these centers or institutions (for example, if you’re a physician in private practice), you may need the services of an “independent” or “free-standing” IRB. The sponsor of the research may suggest (or dictate) an IRB for the project.

Getting informed consent

An important part of protecting human subjects is making sure that they’re aware of the risks of a study before agreeing to participate in it. You must prepare an Informed Consent Form (ICF) describing, in simple language, the nature of the study, why it is being conducted, what is being tested, what procedures subjects will undergo, and what the risks and benefits are.

Subjects must be told that they can refuse to participate and can withdraw at any time for any reason, without fear of retribution or the withholding of regular medical care. The IRB can usually provide ICF templates with examples of their recommended or required wording.

Prior to performing any procedures on a potential subject (including screening tests to see if they qualify for the study), you must give the ICF document to the subject and give her time to read it and decide whether she wants to participate. The subject’s agreement must be signed and witnessed.

The signed ICFs must be retained as part of the official documentation for the project, along with laboratory reports, ECG tracings, and records of all test products administered to the subjects and procedures performed on them. The sponsor, the regulatory agencies, the IRB, and other entities may call for these documents at any time.

Consider using data safety monitoring boards and committees

For clinical trials of products that are likely to be of low risk, investigators are usually responsible for being on the lookout for signs of trouble (unexpected adverse events, abnormal laboratory tests, and so forth) during the course of the study.

But for studies involving high-risk treatments (like cancer chemotherapy trials), a separate data safety monitoring board or committee (DSMB or DSMC) may be set up. A DSMB may be required by the sponsor, the investigator, the IRB, or a regulatory agency.

A DSMB typically has about six members (usually expert clinicians in the relevant area of research and a statistician) who meet at regular intervals to review the safety data acquired up to that point. The committee is authorized to modify, suspend, or even terminate a study if it has serious concerns about the safety of the subjects.

Getting certified in human subjects protection and good clinical practice

As you’ve probably surmised from the preceding sections, clinical research is fraught with regulatory requirements (with severe penalties for noncompliance), and you shouldn’t try to “wing it” and hope that everything goes well. You should ensure that you, along with any others who may be assisting you, are properly trained in matters relating to human subjects protection.

Fortunately, such training is readily available. Most hospitals and medical centers provide yearly training (often as a half-day session), after which you receive a certification in human subjects protection. Most IRBs and funding agencies require proof of certification from all people who are involved in the research. If you don’t have access to that training at your institution, you can get certified by taking an online tutorial offered by the NIH.

You should also have one or more of the people who will be involved in the research take a course in “good clinical practice” (GCP). GCP certification is also available online (enter “GCP certification” in your favorite browser).