Question19: Please, list a CRA’s responsibilities in finalizing the study?

Answer: A CRA must be at the site to do a closeout visit. It would be extremely unusual to try to close out a site without being there in person. Following are the list of CRA responsibilities in finalizing the study:

1. The CRA should make sure that all the case report forms, as well as any corrections or query forms, are complete, in order and ready for storage.

2. If there are still study drug supplies at the site, the CRA should complete a final inventory at the closeout visit. The study drug should then be packaged for return to the sponsor, according to company policy. A copy of the drug inventory form should be placed in the investigator’s study file.

3. The CRA must thoroughly check the investigator’s study document file at this visit. It is wise to use a checklist to ensure that noting is overlooked. All documents must be present, including appropriate re-approvals and correspondence form the IRB. If there were protocol amendments during the study, or amendments to the informed consent form, all versions should be in the file, including their dates of use. Informed consent forms for each subject must be present. The CRA should double-check to be sure they were all signed and dated appropriately. There should be documented for any protocol variations, whether they were previously approved or not. The investigator brochure should be available on or with the file. If any documents are missing from this file, the CRA should help the investigative site to obtain copies.

4. The CRA should verify that Investigator’s final report to the sponsor and the IRB were done, collect copies for the sponsor, if appropriate, and ensure that the reports are in the investigator study file. This report should include an enrollment summary, including the number of subjects entered, those who completed those who dropped out and their reasons for dropping out. It will also include information about adverse events and any other information relative to the trial at that site. The investigator will also make a final report to the IRB. It will contain the information above, in addition to any other information specifically requested by the IRB.The investigator must also notify the institution that the study is complete, if appropriate.

5. Since this is probably the last visit the CRA will make the investigative site for the trial, any outstanding business or issues should be resolved before the study closeout is complete. Any loose ends should be resolved and taken care of before the site is completely closed. The CRA should verify that all appropriate grant monies have been paid or requested. Be sure that the amounts are in agreement between the investigator and the sponsor. If there are unused study materials at the investigative site (case report forms, unused laboratory kits, etc.), they should be returned or disposed of according to the sponsor’s direction. Any outstanding issues from previous visits, or issues that arose during sponsor review, should be resolved before the study is closed out at the investigative site. If not documented elsewhere, a note detailing the resolution should be put in the investigator’s study file.

6. The CRA should discuss record retention with the investigator. Not only do the records need to be stored and maintained, but also there must be a record of where they are stored. According to the regulations, records must be kept for two years after the New Drug Application (NDA) is approved for marketing, or, if an NDA is not filed or disapproved, for two years after the investigation is discontinued and the FDA notified. However, most sponsors expect the investigator to retain all study records until notified by the sponsor that they may be disposed of; this will usually be in the contract that the investigator signed before starting the study. The CRA must be sure that the investigator and site personnel are aware of and understand the retention period

7. The CRA must complete a visit report after this site, as for any other visit. Many companies have a special visit report for closeout visit. This report documents that the study was officially closed. In the final report, the CRA should verify that everything was checked, found complete and prepared for storage. If there were any outstanding issues from previous visits, the resolution of those issues should be documented in this visit report. The CRA should be sure that the report is clear and does not leave any unresolved loose ends.

Study Termination Checklist

In-house

      Notify regulatory department when all patients are off drug and study is terminated

      Send randomization sheets to investigators, if appropriate (only after all study documents are in-house)

      Send clinical data and statistical summary to investigators, if appropriate

      Prepare final study reports

Field

      All CRFs collected, corrected and in-house

      No outstanding data for serious adverse events, deaths, or pregnancies

      Drug collected, inventoried and returned to sponsor

      Investigator files complete and investigator instructed regarding storage

      Drug reconciled from inventory and shipping invoices

      Investigator briefed on procedure if notified of FDA audit

      IRB notified of termination

      Study file complete and ready for audit