Risk Management

Adverse Events in Clinical Research

Anne M. Menke, RN, PhD, OMIC Risk Manager

Just as with care provided outside of research, subjects who participate in clinical trials can experience complications from the study intervention. Federal regulations use the term “adverse events” to describe these outcomes and define them in intentionally broad terms. In drug trials, for example, an adverse event would include any adverse change from the patient’s baseline condition, including any abnormal clinical laboratory test value, which occurs during the course of the study, whether related to the study medication or not. Management of adverse events in clinical research raises questions about who provides and pays for care when adverse events occur.

Q When is an investigator required to provide care for adverse events?

A The FDA issued a guidance document for investigators that contains non-binding recommendations.1 It states that investigators should provide reasonable care for any adverse events related to trial participation. If the investigator does not possess the necessary expertise, the investigator should make sure that the subject is able to obtain the needed care from a qualified practitioner. The care should continue until any emergency condition related to the study intervention is resolved, whether the condition develops during the study or after it ends. The claimant in the Closed Claim Study alleged that the principal investigator (PI) abandoned her by referring her to a hospital after an adverse event occurred instead of performing the needed surgery herself. The PI was a retinal specialist and had the requisite expertise to perform the vitrectomy. The subject, however, was unemployed and without insurance, and the PI, who was an employee of the research center, did not have the authority to provide care in these circumstances. Since endophthalmitis was a foreseeable risk of an intravitreal injection, the PI should have clarified in advance with the research center and the study coordinating center what care she would be authorized to provide in the case of an adverse event. Once she learned that the care she could provide was limited to office-based interventions, she should have identified retina specialists and hospitals willing to provide further care.

Q Who pays for the care in the case of an adverse event?

A Federal regulations governing informed consent stipulate that subjects who face more than minimal risk should be told what compensation and medical treatments, if any, are available for injuries arising from study procedures and where more information may be obtained. The claimant in the Closed Claim Study complained that the consent form contained conflicting information about what care would be provided. The form stated that tests related to the study would be free, but that the subject or subject’s insurance company would be responsible for the costs of study-related treatment, office visits, and general eye care. The consent form then went on to explain that some costs and treatment might not be covered by the subject’s health plan, but if they were not, they would be covered by the study. The claimant informed the investigator at the outset that she had no insurance, and it appears that she believed the study would pay for her care. Her complaint letter did not reference a later section of the consent form, which stated that, in the event of an injury, she would receive medical treatment but would be responsible for the costs and that no money was available to compensate her for an injury. The form did not explain whether the risks detailed in the document were considered an injury. Consent forms can be confusing. The National Cancer Institute developed a research consent form template that meets federal requirements but uses simplified language. It states, in part, “The study sponsors will not pay for medical treatment if you are injured or hurt because you took part in this study. Your insurance company may not be willing to pay for injury from the study. If you have no insurance, you will be responsible for any costs [related to an injury].” The template further explains that if subjects feel an injury was a result of medical error, they keep all of their legal rights to seek payment for an injury even though they were in a study.2 Ophthalmologists may benefit from using similar language to ensure that information about adverse events is clearly communicated in the protocol, consent form, and consent process.

  1. FDA. “Guidance for Industry: Investigator’s Responsibilities—Protecting the Rights, Safety, and Welfare of Study Subjects.” http://www.fda.gov/downloads/Drugs/…/Guidances/UCM187772.pdf.
  2. National Cancer Institute. NCI Consent Form Template. http://www.cancer.gov/clinicaltrials/conducting/simplification-of-informed-consent-docs/.




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