An essential mandate for any physician caring for a patient who is in a clinical trial is to always put the patient's safety and care first. This mandate is true for a physician who is not involved with the clinical trial as well as the physician who is the investigator. There are occasional circumstances during which the needs for caring for a patient are at odds with the clinical trial. For example, a participant's physician may want to stop the study treatment (eg, if there is a concern that a significant adverse effect is due to the study drug) or break the blind of a study to learn what treatment a patient has been receiving (eg, if the patient has become seriously ill and the physician needs to know all treatments the patient has been receiving).
It is not the responsibility of the noninvestigator physician whose patient is in a clinical trial (or considering enrollment) to answer specific questions about the trial. This is the responsibility of the investigator and clinical trial coordinator. However, the physician can provide the patient with a list of key questions to ask before participating in a clinical trial The Clinical Trial Participation Experience Patients have different reasons for wanting to participate in clinical trials. Some want access to the newest treatments, which they hope will be more effective than the current standard of... read more . Concerns raised by the physician can be addressed with the trial investigator or study coordinators.
A participant's physician may not share a participant's private information with the investigator or clinical trial coordinator unless the participant has granted permission. The Health Insurance Portability and Accountability Act (HIPAA) privacy rule protects the privacy of clinical research participants. The U.S. Department of Health and Human Services (HHS) provides information on how HIPAA privacy rules apply to clinical research. In summary, these rules require that a patient's personal health information, such as information in a patient's medical chart or test results, can only be disclosed for research purposes and only if the patient has granted specific written permission. (See HHS.gov for further details of the HIPAA privacy rule.)
Adverse Events and Concurrent Illness
Adverse events (AEs) are any unfavorable medical occurrences temporally associated with the participant's involvement in a clinical trial, whether or not it is considered related to the investigational treatment or participation in the trial. Adverse events include any
Abnormal physical examination finding
Abnormal laboratory finding
Patients enrolled in a clinical trial are asked about any adverse events at each encounter with the clinical trial team (investigator or clinical trial coordinator). An important aspect of a clinical trial is the careful collection and reporting of adverse events. Usually the trial team is asked to assess whether an adverse event is related to the study drug. In addition, clinical trial programs often use standardized search terms from the Medical Dictionary of Regulatory Activities (MedDRA). The results of these objective searches help detect potential adverse events and are provided to regulatory agencies as part of the submission process for drug approval. MedDRA searches may identify safety concerns that have not otherwise been identified during the clinical trial program.
FDA MedWatch allows physicians as well as patients and consumers to report adverse events directly to the U.S. Food and Drug Administration (FDA). FDA MedWatch is for any FDA approved or unapproved prescription or over-the-counter medicine, biological such as blood products, medical device, nutritional product such as infant formula and medical food, cosmetic, food, and beverage, regardless of whether it is part of a clinical trial.
A serious adverse event (SAE) is any adverse event that
Results in death
Is life threatening or places the participant at immediate risk of death
Requires or prolongs hospitalization
Causes persistent or significant disability or incapacity
Results in congenital anomalies or birth defects
Is another condition that investigators judge to represent significant hazards
A physician caring for a patient who is enrolled in a clinical trial should inform the investigator of an SAE as soon as possible. The investigator is required to report any SAE to the sponsor within 24 hours from the time the investigator learns about the event. In most clinical trials, the sponsor must report the SAE to the regulatory agency. SAE reporting for investigator-initiated trials is carried out according to terms in the contract with the sponsor and may be slightly different from the phase I to IV clinical trial programs.
Breaking the blind usually occurs after all participants have completed the trial and data collection and monitoring have been completed. However, for an individual patient, breaking the blind ("unblinding") can be done if required for proper care of a patient, and the physician caring for the patient can document that it is essential to know what treatment the patient has been receiving. For example, if the patient has become seriously ill and the physician needs to know all treatments the patient has been receiving, the caring physician must contact the clinical trial investigator and request that the blind be broken. In blinded trials, the investigator does not know the treatment assignment, so the request to unblind a participant is usually the decision of the sponsor (eg, pharmaceutical company, U.S. Department of Veterans Affairs [VA], the National Institutes of Health [NIH] other funding agency). Guidance for unblinding is often provided in the trial protocol and the informed consent document.
When a study patient comes for care
When a study patient visits a health care practitioner who is not involved in a trial (and may not even be in the same organization as the trial site), communication among the patient, the health care practitioners, and the clinical trial team is important to ensure optimal patient care as well as clinical trial integrity. Practitioners should become familiar with the key elements of the trial. Practitioners can get this information from the patient's consent form or summary card or by contacting the trial study team. Contact information is in the consent form or summary card given to the patient.
Trial participants: Participants should tell their health care practitioners about the clinical trial and provide a copy of the consent form or summary information card from the trial. Participants should have the study team's contact information available during appointments with their health care practitioners.
Health care practitioners: Practitioners should know enough about the trial to consider whether trial interventions could affect the patient's health. Before recommending trial discontinuation, the health care practitioner should discuss concerns with the trial staff and patient/participant. Patient discontinuation may unnecessarily jeopardize the patient's trial data. Some clinical trial biomarkers may be blinded to the participant and the study staff. Whenever clinically feasible, practitioners should not order such biomarkers because knowing results of those biomarkers compromises study blinding and jeopardizes the validity of that patient's trial data. Practitioners may also be able to determine whether the patient has experienced a trial endpoint or a possible adverse event. Practitioners should report potential endpoints and adverse events to the study team who, in turn, know the processes for reporting through the clinical trial protocol.
Trial staff: The trial staff must balance ensuring that the trial does not interfere with necessary clinical care for the participant and maintaining trial integrity. They are obligated to ensure that the trial participants know enough about the trial to discuss it with their practitioners. Clinical trial staff also need to be available to answer practitioners' questions. If they determine that the practitioner has identified a potential adverse event or a study endpoint, the trial staff must execute the appropriate processes, such as records release forms, to access the data for reporting to the sponsor.
After conclusion of a clinical trial, the primary responsibility for follow-up care usually returns to the patient's personal physician. After a randomized, controlled trial, at the conclusion of patients' enrollment in a trial, they are usually taken off the study drug regardless of whether they received an active study drug, active comparator, or placebo. In fact, there is often a delay before they learn which arm of they study they were randomized to and, therefore, whether they received an active study drug, active comparator, or placebo. This delay is due to the requirement that the blind for a trial not be broken until after the last subject has completed the trial and collection and monitoring of the data has been completed. Occasionally, a study drug will be made available to patients who participated in a clinical trial, either within or outside of a formal extension trial. Patients who wish to consider this option should inquire about this possibility before enrolling in the trial. For approved drugs, the treating physician can decide whether to prescribe for an unapproved ("off-label") use based on evidence of drug effects and patient factors.
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
The Center for Information and Study on Clinical Research Participation (CISCRP): Information for the public, patients, and other stakeholders in the clinical research process about CISCRP's media outreach and awareness campaigns and live educational events; study volunteer appreciation programs; patient advisory boards and custom research assessing patient health journeys and study volunteer experiences; and plain language clinical trial results summaries
National Institutes of Health: Clinical Research Trials and You: Information for patients and health care practitioners about clinical trials and how to find appropriate trials
Listings of clinical trials are available at: