As I understand Sponsor even has an obligation to monitor the trial as well as ensuring the Investigator is following protocol and is keeping accurate records etc.
In short it seems yes sponsor will be aware of trial progress, but not data that reveals the identity of individual patients and which trial arm cohort they belong to. In other words the randomisation and blinding is maintained all the way to the end of the trial when data is then released for analysis.
There are no FDA regulations that would prohibit a sponsor or their monitors having access to subjects' medical records. Indeed, access to subjects' medical records is clearly implicit in the regulations and in our GCP guidance, the ICH E-6 Good Clinical Practice: Consolidated Guidance.
In my opinion, the regulatory basis to support a sponsor's access to patient medical records would rest most heavily on the regulatory obligation of the sponsor to ensure adequate monitoring under Title 21 of the Code of Federal Regulations, Parts 312.50 and 312.56 (21 CFR 312.50 and 312.56). Specifically 21 CFR 312.56 states:
The sponsor shall monitor the progress of all clinical investigations being conducted under its IND.
A sponsor who discovers that an investigator is not complying with the signed agreement (Form FDA-1572), the general investigational plan, or the requirements of this part or other applicable parts shall promptly either secure compliance or discontinue shipments of the investigational new drug to the investigator and end the investigator's participation in the investigation."
The record keeping requirements for investigators are found at 21 CFR 312.62(b), which states:
"(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." The sponsor would necessarily need to verify that case histories---including medical records--are being maintained. Adequate monitoring would therefore necessarily include direct access to patient medical information pertinent to the investigation. This interpretation of what is required for adequate monitoring by the sponsor is further supported in our guidance. For example, the ICH-E6 makes it quite clear that regulators, sponsors, IRBs, monitors etc. should have direct access to medical records:
6.10 Direct Access to Source Data/Documents
"The sponsor should ensure that it is specified in the protocol or other written agreement that the investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspection(s) by providing direct access to source data/documents."
Direct access is defined as:
"1.21 Direct Access: Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsors, monitors, and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects' identities and sponsor's proprietary information."
Section 5.18.4(m) goes on to describe adequate monitoring to include:
"Checking the accuracy and completeness of the CRF entries, source data/documents, and other trial-related records against each other. The monitor specifically should verify that: (i) The data required by the protocol are reported accurately on the CRFs and are consistent with the source data/documents."
Source Data and Source Documents are defined as follows:
"1.51 Source Data: All information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies)."
"1.52 Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial)."
One thing to keep in mind is that the informed consent document is required to include "A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records." (See 21 CFR 50.25(a)(5).) Both the protocol and informed consent document are reviewed by the IRB prior to initiation of the study, and thus provide opportunities for the IRB to be apprised of both the sponsor's and monitor's expected access to the subjects' records and the information to be provided to the subjects about such access.
In conclusion, even though the regulations themselves don't explicitly state that a sponsor shall have access to subjects' medical records, this expectation is implicit in the regulatory requirements for adequate monitoring and is further suggested in the ICH E-6 guidance.
AI
