A number of years ago I was sent to co-monitor with several monitors in order to meet an interim safety analysis. My first question was “where are the medical records? One of the monitors laughed and said, “we’re in Any town, USA and they never have medical records in Any town”, USA. I explained that I had been a regional monitor to Any town, USA for over 20 years and medical records were always available. The monitor said, “that was then, this is now.”
Since every protocol, in keeping with the CFR requirements, indicates the need for complete and accurate medical records, it was not clear to me how a safety analysis could be performed when there were no medical records to review. It was also unclear to me how subject eligibility had been determined. The monitors gave me a stack of source documents to review in an attempt to locate some of this information.
Another instance this past year, while taking over several sites from previous Clinical Research Associates in Anytown, USA, I asked for the medical records at the first research site visited. The site’s research staff told me, “we asked and we were informed we did not need medical records”. After my initial shock wore off, I explained that medical records are always required for a subject’s participation in a clinical trial. The site’s research staff countered, it was okay with the other CRAs when it was explained that many of their subjects did not have a primary physician, nor medical insurance and had not seen a physician in a long time.
I further clarified that without medical records, it is difficult at best, if not impossible, to determine the eligibility of a potential study subject for a specific clinical trial. It is also difficult to determine if the subject experienced an adverse event during participation in the clinical trial. Did the subject have a base line condition (i.e., frequent headaches) or did the subject actually have a headache as a new medical condition?
Next, I reviewed with the site research staff Form FDA 1572, #9, Commitments, which holds the Principal Investigator, and delegated study staff, accountable for maintaining study records. It states, “I agree to maintain adequate and accurate records in accordance with 21 CRF 312.62 and to make those records available for inspection in accordance with 21 CFR 312.68.”
We also reviewed CFR 312.62 Investigator recordkeeping and record retention, “(b) Case histories. An investigator is required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation. Case histories include the case report forms and supporting data including, for example, signed and dated consent forms and medical records including, for example, progress notes of the physician, the individual’s hospital chart(s), and the nurses’ notes. The case history for each individual shall document that informed consent was obtained prior to participation in the study.”
Since there were no case histories or medical records available for review, I suggested corrective measures and provided the sites with several different options to obtain a potential study subject’s medical history:
1). Medical information could be obtained directly from the potential study subject. The subject could voluntarily provide medical records to the research center, while always ensuring compliance with HIPAA regulations.
2). Sites were shown how in many cases the study source documents could be used as a tool to obtain medical history information, as medical conditions and medications are information generally requested by the protocol.
3). I provided sites with a generic medical history intake form that they could adapt for their site’s use. Sites did not have a clinic intake form, nor was there any documentation that the potential study subject’s medical history had ever been discussed by the site research staff, including the Principal Investigator (PI), with the potential study subject. I explained to the site research staff, that this information is critical to a potential subject’s participation in a clinical trial.
4). Sites were asked to document how eligibility was determined for each subject randomized into the clinical trial.
The same information provided to the first site was provided to the other seven (7) sites. Only one (1) of the eight (8) sites had medical records for subjects being considered to participate in the clinical trial.
It was noted during subsequent site visits that many of the methods suggested were being implemented for new potential study subjects being considered for participation in the research study.
In conclusion, it is the responsibility of the CRA to verify that study subject medical records exist for each subject randomized into a clinical trial. If there is a lack, or missing medical information, the CRA is responsible for ensuring information regarding the requirements for potential study medical records is provided to the site research staff.
The CRA is also responsible to ensure study oversight by the PI: for confirming the subject met the study inclusion/exclusion criteria; that informed consent was obtained prior to any study procedures and documented in the medical record; to determine if there are baseline conditions, if prescribed medications are being taken (including over the counter medications and herbal supplements that are allowed and not prohibited); there is documentation in the source documents for each potential study subject indicating when the information was obtained and by whom. The documentation should include the decision for the potential subject to be included in the study and should be signed and dated by the person obtaining this information and determining eligibility.
Medical records assist the PI in determining, along with the other screening criteria, if the potential subject is eligible to participate in the specific clinical trial. These medical records generally include surgical procedures, diseases, allergies, hospitalizations, chronic medical conditions (e.g., asthma), medications, including over the counter medications, and the medical reason the medication is being used. Some medical history forms also include social history and demographic information. Much of this information is requested in the source documents as well as the electronic case report form used to enter the data from the source documents.