New Guidance Documents Available for When Subjects Withdraw from Clinical Trials

By Susan J. Matthees—

FDA and the Department of Health and Human Services Office for Human Research Protections (OHRP) recently announced the availability of two guidance documents intended to help investigators, researchers, sponsors, and IRBs understand how data already collected may be used after a subject discontinues participation in a clinical trial.                                                             

FDA’s guidance document, “Guidance for Sponsors, Clinical Investigators, and IRBs Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials,” explains that under the existing regulatory scheme, if a subject withdraws from a study, the data collected on that subject up to the point of withdrawal generally must remain in the study database.  FDA states that “[c]omplete removal of data, possibly in a non-random or informative way, raises great concerns about the validity of a study.”  However, once a subject withdraws, an investigator may only continue to gather data with the subject’s permission.  The “investigator may ask a subject who is withdrawing whether the subject wishes to provide continued follow-up and further data,” distinguishing with the subject the “study-related interventions and continued follow up of associated clinical outcome information.”  The subject must agree and provide informed consent before the investigator can continue to gather data. 
 
If the subject does not give permissions to the investigator to collect further data, the investigator may not access the subject’s medical record.  But, the guidance document makes clear that the investigator may consult public records, including death records, to obtain follow-up data.   
 
OHRP’s draft guidance document, “Guidance on Important Considerations for When Participation of Human Subjects in Research is Discontinued,” does not discuss whether an investigator should consult public records to obtain follow-up data.  However, like FDA’s guidance document, OHRP’s draft guidance document states that an investigator may continue to analyze data already collected from a subject even after the subject withdraws from participation in the research.  OHRP’s draft guidance document also provides details on both the meaning of “participation” and the types of data that can be collected.   

The OHRP draft guidance states that OHRP “interprets subject participation” to mean any of the following activities:  interviewing the patient, taking a blood sample, administering a drug, “collecting individually identifiable private information . . . collecting individually identifiable biological specimens” from the subject, or “using or testing individually identifiable biological specimens already collected by the investigator (e.g., performing a genetic test on a tissue specimen already collected from a subject).”  OHRP does not consider the following activities to be subject participation:  “[a]ny continued analysis by the investigator of individually identifiable private information about the subject that was obtained by the investigator prior to the subject’s decision to discontinue participation in a study” or “continued analysis . . . of data that was derived by an  investigator through a previous use or test of a subject’s individually identifiable biological specimens prior to the subject’s decision to discontinue participation.” 

The OHRP guidance document also recommends that whenever a subject decides to discontinue participation, the investigator document the circumstances.  The investigator should specify “[w]hether the discontinuation of the subject’s participation results from a decision by the subject or by the investigator,” whether the discontinuation is full or partial, and “[t]he reason for the discontinuation.”