Assessment of Adverse Events in Clinical Trials

Clinical trials use drugs that have undergone extensive testing in animals, but limited testing in humans; thus, unpredictable adverse events are always possible. Adverse events are defined as unfavorable signs or symptoms that result from a particular treatment or procedure (www.cancer.gov), and they must be assessed correctly to ensure accurate reporting when approval of a drug or procedure is being sought. This article focuses on assessment and care of patients enrolled in investigational studies. Each site undertaking a clinical trial is responsible for accurate and timely reporting of adverse events. These events are collected to determine the safety profile of the drugs being studied, to assess the risks and benefits of the drugs, and to report information about side effects for possible later marketing. The FDA will examine the data to determine if the risks of the drugs outweigh the benefits.

Examining adverse events

Adverse events can be expected or unexpected. An expected event is one that is anticipated based on previous clinical experience. An unexpected event is one that is unforeseen and has not been previously reported in the investigator brochure or on the package insert. An adverse event can become serious, and it is reportable to the drug company, the Institutional Review Board, and the FDA when use of the drug results in death, is life-threatening, or leads to disability or hospitalization.

According to an article published in the Journal of Clinical Oncology (http://tinyurl.com/n4mjhz), low-grade adverse events are often underreported in phase II clinical trials. This may be because the information being reported must be prioritized to the most clinically relevant; thus, non-threatening adverse events often go unreported. There is also an underreporting of recurrent adverse events. Efforts need to be made to report recurrent events because the grades will often change. It also can be difficult in some cases to attribute an adverse event to the drug being tested; thus, a comprehensive assessment tool is essential in helping to make that determination.

Our assessment tool

At our institution, each of our protocol groups uses an assessment tool. We call ours an intake sheet. The physicians can use this tool to make sure they agree with the nurses’ assessments and can dictate their note from the copy we give them. We also send a copy to medical records. The intake sheet contains a section for the patient’s name, date, cycle and day of the study, and the study drug and dose that is being administered. There is a section that includes vital signs and performance status, for which we use the Karnofsky Scale or the Eastern Cooperative Oncology Group Performance Status Scale. We also have separate sections for medications and adverse events. Adverse events are listed according to the ones we most frequently encounter (eg, fatigue, pain, nausea, vomiting). The list is derived from the National Cancer Institute’s (NCI) Common Toxicity Criteria, version 3 (http://tinyurl.com/mswxto), which is a small pocket-sized book that contains different grades of these toxicities. Our intake sheet also has a column for start date, stop date, frequency of occurrence, medication used, and attribution to drug. When monitors come to review the charts, they are able to easily verify whether the adverse events experienced are resulting from the drugs being used or from another cause. Use of an assessment tool such as our intake sheet facilitates consistent reporting of adverse events by both our nurses and physicians.

Take-home message

We feel our intake sheet has helped ensure accurate reporting of drug adverse events at our institution. If a drug’s adverse events are over or understated, it could prevent beneficial drugs from making it to the market or result in potentially harmful drugs being marketed. Adverse events need to be reported consistently and correctly to ensure drugs are brought to market properly, and nurses play a vitally important role in making this happen. Developing an assessment tool like an intake sheet and using NCI’s Common Toxicity Criteria can help nurses overcome this challenge.

Roxanne Williams-Truax, RN, BSN, OCN, is a research nurse clinician with the Duke Clinical Cancer Trials Services at Duke University Medical Center.