Patient Safety Comes First in Clinical Trials

Karen E. Woodin, PhD

In This Article


During the past few years, a number of abuses have been committed in clinical trials. Investigators have been disqualified for falsifying data and for noncompliance with FDA regulations; some of these investigators are even serving jail sentences for disregarding good clinical practices. Internal Review Boards (IRBs), too, have paid a toll, as the FDA and the Office of Protection from Research Risk have required them to halt enrollment in ongoing clinical trials and cease review of new trials until IRBs rectify their abuse of procedures and are able to operate according to the applicable regulations.

In all these situations, the safety of trial subjects either was or could have been compromised. In light of these problems, it has become even more critical to have in place systems and procedures that protect the rights and welfare of clinical trial subjects and to ensure that safety is paramount as we strive to develop and bring new drugs to market in a shorter time period than ever before.

In both clinical trials and clinical practice, the safety and well-being of the patient must always come first and each patient must be treated according to his or her illness and needs. In clinical trials of new drugs, however, all patients have to be treated according to a single protocol. The protocol is the same for each patient or subject enrolled in the trial and is not to be changed according to individual patient differences. The use of one protocol ensures that data collected are unbiased and meet appropriate statistical considerations, and it also leads to definitive answers to the questions being asked in the trial. Without appropriate statistical significance for efficacy and safety parameters, new drugs will not be allowed to be marketed.

There are many regulations covering patient safety during clinical trials, including the use of informed consent and the review and approval of all trials by IRBs. As another safeguard, sponsors must ensure that physicians involved in their studies are qualified by training and experience to conduct clinical trials.

Data safety monitoring committees (DSMCs) have been used in clinical trials for a number of years and lately are being used more frequently, constituting one more safeguard in the ongoing effort to improve the protection of subjects in clinical trials. A DSMC, which is established by the pharmaceutical company seeking marketing approval of one of its drugs, monitors safety on an ongoing basis during clinical trials. Sometimes they are called by other names, such as data safety monitoring boards, independent review committees, and independent monitoring boards. Regardless of the name, these committees provide an additional safeguard for study subjects. In general, DSMCs are used for multicenter trials, especially when the medical condition being studied has a high mortality or morbidity rate, such as AIDS or cardiac conditions. To maintain the statistical integrity of a clinical trial, the sponsor must wait until the trial has been completed before looking at the data; at the same time, however, the data collected throughout the trial may yield valuable information that can have an impact on patient safety. The use of a DSMC allows for regular safety monitoring while keeping the sponsor of the trial unaware of early results.

The sponsor of the clinical trial initiates formation of a DSMC, usually before the trial begins. Some sponsors select all the members, while others select only a chairperson. The chairperson, in turn, selects the other members, thereby lessening potential sponsor/DSMC conflict of interest. Membership consists of physicians who are expert in the disease being studied and who also have clinical trial experience, a statistician, and perhaps an ethicist or patient advocate. The committees are not large, perhaps 5 members, and generally consist of an odd number of members for majority voting purposes. Although representatives of the sponsor may attend committee meetings, they are present only as information resources, not as voters. A statistician from the sponsoring company may attend meetings to explain the statistical methodology and help in the interpretation of the data, but this person is not usually the statistician who will analyze the trial data for the sponsor.

The use of DSMCs is voluntary, except when the trial is using a waiver of consent -- that is, when subjects are confronted with a life-threatening condition, are unable to give consent, and there is insufficient time to contact family members. Under FDA rules for waived consent (21 CRF 50.24), a DSMC is required for these trials.


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