Let’s Destroy Our Obsolete Paper Study Records

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The advent of electronic study records has dramatically slowed the growth of paper study records. Nevertheless, there are probably millions of boxes of obsolete clinical study records, costing study sites tens of millions of dollars each year. While there are much larger problems in clinical research, storing obsolete study records is a totally unnecessary cost. They are also a thorn in the side of site/study sponsor relationships.

U.S. Regulations and Guidance

The U.S. Code of Federal Regulations states:

An investigator shall retain records required to be maintained under this part for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated; or, if no application is to be filed or if the application is not approved for such indication, until 2 years after the investigation is discontinued and FDA is notified." [CFR 312.62(c)]¹

The U.S. Code of Federal Regulations does not explicitly require notification of the FDA in a timely manner that an investigation has been terminated so, strictly speaking, if the study sponsor does not so notify the FDA, the sponsor is not obligated to notify study sites when records can be destroyed. However, the following FDA guidance states that study sponsors should make such notifications:²

Essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period, however, if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained (see section 5.5.12). (4.9.5)

If the sponsor discontinues the clinical development of an investigational product, the sponsor should notify all the trial investigators/institutions and all the regulatory authorities. (5.5.9)

The sponsor should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify the investigator(s)/institution(s) in writing when the trial-related records are no longer needed. (5.5.12)

Study sponsors conduct clinical studies pursuant to an Investigational New Drug (IND) application to the FDA. INDs eventually expire or are withdrawn, at which time, study sites could destroy their records, provided they know when it closes. However, study sponsors consider IND information confidential. Neither does the FDA provide this information to study sites, per a personal FDA email communication dated February 28, 2024:

Please understand that due to confidentiality laws, we cannot provide information related to drug applications that may have been submitted. All information on an unapproved application or investigational application is confidential and belongs to the manufacturer/sponsor of the application. We recommend that you contact the sponsor to request additional updates as information about a drug being investigated is only releasable by the sponsor.

On a much more positive note, in a personal email communication dated February 27, 2024, the FDA instructs study sites how to obtain relief from the burden of obsolete paper study records:

You may also want to consider sending a certified letter to those companies, including a statement that you plan to destroy the paper documents as of [date greater than 30 days from letter date], unless they contact you and indicate that the study documents are still needed for submission or review by [date 30 days from letter date]. Although not required, you may want to consider electronically archiving the study records for those companies that have failed to respond to your certified letters, before destroying the paper copies. FDA believes that study documents captured on paper can be archived as electronic copies, if the electronic copies are “certified copies.” FDA defines certified copies in the guidance regarding the use of computerized systems in clinical investigations. This guidance is accessible at Computerized Systems Used in Clinical Investigations and the definition of certified copies it includes reads as follows: “Certified Copy: A certified copy is a copy of original information that has been verified, as indicated by a dated signature, as an exact copy having all of the same attributes and information as the original.”

While FDA guidance and communications do not carry the legal weight of regulations, study sponsors should have a good reason to deviate from them.

Contractual Obligation to Notify

MAGI’s Clinical Trial Agreement Template includes a representative provision for records storage:

8. RECORDS MAINTENANCE AND RETENTION.

Investigator and Institution will maintain adequate and accurate records relating to the disposition of the Study Drug and/or Study Device and the performance of all required Protocol procedures on Study subjects, including but not limited to, Source Documents, medical records, charts pertaining to individual Study subjects, CRFs, accounting records, notes, reports, and data.Institution will retain these documents for the time required by applicable law and regulation. Sponsor shall provide written notice to Institution to notify of the events stated in 21 CFR 312.62(c) so that Institution may comply with its document retention obligations stated herein. Institution will notify Sponsor in writing prior to destruction of any Study-related records and, if requested by Sponsor, shall continue to retain the documents, with a reasonable additional fee to be paid by Sponsor.

Study sites should consider the cost of storing study records over the entire life of a clinical investigation, which may consist of numerous studies over many years, as well as the cost of issuing notices of pending destruction, electronic archiving, and records destruction. To limit risk, the fee for records storage should cover a specified number of years, after which, payment of a new fee would be required for another specified number of years.

Expiration of the term of storage provides a convenient date to review the need for continued storage. Payment of a storage fee does not relieve the study sponsor of its affirmative duty to notify the site when records can be destroyed.

The MAGI provision above includes the same FDA-notification loophole discussed above. However, every contract—including clinical trial agreements—includes a duty of good faith and fair dealing.

This duty requires that neither party will require the other party to undertake undue or unnecessary burdens to perform under the terms of a contract. Storing obsolete study records beyond their useful life imposes an unreasonable and wasteful burden on the site. Therefore, study sponsors have an affirmative duty to inform study sites in a timely manner when they may destroy obsolete study records, ship them to the study sponsor, or continue storage with fair compensation.³

Study sponsors should maintain a role-based email address, e.g., records.storage@company.com, for such communications. To minimize the burden of these notifications on both parties, study sponsors should proactively notify sites when a clinical investigation has terminated or maintain a password-protected list of discontinued investigations. A single organization could maintain these data for all parties.

Notification of Pending Records Destruction

Per the above FDA instructions, study sites should identify paper records that may be obsolete, beginning two to five years after closure of a study at the site. The site can then notify the study sponsor of the pending records destruction and offer four choices:

1. The records must continue to be stored, per regulatory requirements.
2. The records may be archived electronically (at the study sponsor’s cost) and then destroyed.
3. The records may be shipped to the study sponsor’s location, at the study sponsor’s cost.
4. The records may be destroyed.

Study sites should reference their records storage standard operating procedure in these notifications. Destruction of study records is a serious and irreversible step, so study sites must take due care in notifying study sponsors of pending records destruction.

A study site may notify the study sponsor by email of the pending records destruction. If the study sponsor does not respond in a timely manner, the study site can follow up with a certified letter to a suitable person, e.g., the vice president of clinical operations or the general counsel.

Before notifying a study sponsor of pending destruction of study records, study sites should verify that the sponsor still exists and is located at its original address. If the study sponsor still exists and still owns the relevant intellectual property, notification of pending records destruction should be straightforward; however, there are other scenarios:

• The study sponsor has transferred the relevant intellectual property to a different company.To cover this possibility, when notifying the original study sponsor, ask about the current ownership of the relevant intellectual property. The new owner of the intellectual property cannot expect study sites to know about the transaction so, if it wants the study sites to retain study records, it has a duty to so notify them. The original owner may also have the duty to notify the study sites.
• The study sponsor has been acquired by a different company and no longer exists as a separate entity. It should be possible to obtain this information with a bit of internet research. In this scenario, study sites should identify a suitable person at the acquiring company for notification.
• The study sponsor has been liquidated, i.e., no longer exists. It should be possible to obtain this information with a bit of Internet research. Return of a certified letter by the post office will document that proper notification was attempted.

In all scenarios, study sites should fully document the notification process, related activities, decisions and resulting actions.

Conclusion

Study sites may not realize that they must store study records for the life of the clinical investigation, which may consist of numerous studies over many years. Study records do, however, eventually become obsolete, and it may come sooner than expected, e.g., when a study fails to prove safety or efficacy, or the study sponsor fails to secure its next financing.

Storing obsolete paper study records imposes costs on study sites that do not benefit study sponsors. The resources that study sites apply to wasteful records storage could, instead, be applied to improving their conduct of clinical studies. Study sponsors that alleviate sites from wasteful records storage are one step closer to being a sponsor of choice.

References

1. CFR 312.62(c), https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-D/section-312.62

2.“E6(R2) Good Clinical Practice: Integrated Addendum to ICH: Guidance for Industry,” March 2018, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e6r2-good-clinical-practice-integrated-addendum-ich-e6r1

3. Personal communication from Darshan Kulkarni, Principal Attorney, Kulkarni Law Firm

About the Author

Norman M. Goldfarb is executive director of the Site Council and executive director of the Clinical Research Interoperability Standards Initiative (CRISI). Previously, he was chief collaboration officer of WCG Clinical, founded and led the MAGI conferences, and published the Journal of Clinical Research Best Practices.