The 3 Essential Skills Your TMF Team Must Have
Skill #3: How to Evaluate Form FDA 1572
The life sciences industry faces a serious problem—a widespread trial master file (TMF) skills gap. There are simply not enough skilled TMF professionals to support the explosive growth and complexity of clinical research.
That’s where LMK Clinical Research Consulting’s TMF University comes in. LMK’s TMF University is the first and only internationally recognized and accredited certification program for working TMF professionals. TMF University allows TMF professionals of all backgrounds to access real-time and asynchronous remote TMF education courses tailored to meet learners at their level of expertise.
To celebrate the overwhelming success of TMF University and the hundreds of accomplished TMF University graduates, we’ve decided to publish this blog series sharing the three skills we feel your TMF team must have to achieve TMF health. In this final post of the series, we’ll cover how to evaluate one of the most important documents in the TMF: Form FDA 1572.
What Is Form FDA 1572?
The Statement of Investigator, or Form FDA 1572 (1572), is an agreement signed by a clinical trial site investigator assuring the sponsor of a clinical trial that the investigator will comply with FDA regulations pertaining to clinical research. The agreement includes a commitment to furnish important information to the sponsor pertaining to patient safety and data integrity. Per § 312.53 of Title 21 of the Code of Federal Regulations, the sponsor of a clinical trial must obtain a completed and signed 1572 before the investigator can begin research. The responsibility to collect the 1572 is part of the sponsor’s overall oversight requirements that come with investigational new drug application (IND) approval. An IND permits human subject research to be conducted for a treatment candidate.
The purpose of the 1572 is twofold:
- The 1572 provides the sponsor with information about the investigator’s qualifications and the appropriateness of the investigator’s site for the planned research. As investigator selection is a critical component of the sponsor’s regulatory duty to have oversight of the clinical trial, the 1572 is record that the sponsor selected a qualified investigator. Even though the investigator’s role may have the greatest day-to-day intersection with patient safety, the sponsor is just as liable for the safety of clinical trial patients—even if the investigator is thousands of miles away.
- The 1572 informs the investigator of the serious responsibilities they take on when conducting clinical research. Consider Box 9 of the 1572—it contains a lengthy list of commitments that the investigator is making under the Code of Federal Regulations. These include conducting the investigation according to the protocol, obtaining informed consent, obtaining IRB approval, and maintaining inspectable records. An investigator’s signature on the 1572 is a binding affirmation to the content of the form. Submission of a deliberately false statement to the sponsor or FDA via the 1572 is a criminal offence under 18 U.S.C. 1001 and could also lead to debarment from the entire U.S. drug industry.
What Are Some Frequently Asked Questions About Form FDA 1572?
Given the central importance of the 1572 to clinical research and the TMF, the number of questions related to its successful completion, filing, and review are nearly limitless. Below, however, are some questions we are commonly asked related to misconceptions about the 1572. Note that many of these questions and their answers are paraphrased from FDA Information Sheet, Frequently Asked Questions – Statement of Investigator (Form FDA 1572).
- How Should a 1572 Be Completed?
A 1572 may be completed by typing entries directly into the fillable form or by hand-writing information into a blank form after printing. Typed forms are preferred for legibility. The form must be signed and dated by hand or with an electronic signature, although it is most common for the 1572 to be printed, scanned, and signed. If a 1572 is generated electronically in a file system, compliance with 21 CFR Part 11 would be expected. If a wet ink original of the 1572 is to be copied, a certified copy process should be in place.
- What Are the Minimum Qualifications of an Investigator?
Determining the minimum qualifications of the investigator is the responsibility of the sponsor. The sponsor, after all, is the undisputed expert on the investigational product and would therefore have the best insight into who is “qualified by training and experience as appropriate experts to investigate the drug.” In addition to the common-sense training of medical education in the treatment area, guidance suggests a potential investigator have familiarity with human subjects’ protection regulation and good clinical practice regulations. Surprisingly, regulation does not require that an investigator be a physician—although a physician must be, at minimum, listed as a subinvestigator for safety purposes.
- If a 1572 Expires, Does It Need To Be Recollected?
Despite the fact that the form carries an expiration date, there is no need to collect a new form with the new version of the 1572 after it has been released by FDA.
- When Must a New 1572 Be Collected?
There are only two instances when an investigator should complete a new 1572: when a new investigator is added to the study or when a new protocol is added to an IND. According to guidance, the 1572 does not need to be revised or replaced with a new 1572 for the addition of subinvestigators, change of IRB address, or addition of a clinical lab. Record of these changes should be documented in the TMF and investigator site file (ISF). Changes can be accumulated and then applied when a new form is generated.
- Do Study Coordinators Need To Be Included in Box 6?
No. Box 6 is for investigators and subinvestigators based on their regulatory obligations. As study coordinators do not share in these regulatory obligations, they should not be included in Box 6. According to 21 CFR 312.3(b), subinvestigators “e.g., research fellows, residents” assist “the investigator in the conduct of the investigation(s).” Subinvestigators “are part of an investigative team, will assist the investigator and make a direct and significant contribution to the data.” In general, if an individual is performing protocol assessments and contributing to the data via qualitative judgment than they should be included in Box 6. According to guidance, however, “hospital staff, including nurses, residents, or fellows and office staff who provide ancillary or intermittent care but who do not make a direct and significant contribution to the clinical data, do not need to be listed individually.”
- Does the Address on a Subinvestigator’s CV Need To Match Box 3 of the 1572?
The address should match exactly for the purposes of making the subinvestigator’s affiliation abundantly clear. If a subinvestigator’s affiliation to the research site is in any way unclear, a separate affiliation document clarifying the relationship should be generated and filed in the TMF and ISF.
You Can Close the TMF Skills Gap
Despite the critical importance of TMF health, TMF experts have suffered from the harmful notion that TMF management is clerical work and that all TMF professionals are simply document reviewers. But this couldn’t be further from the truth. All of today’s TMF professionals must have advanced skills in project management and clinical operations oversight to achieve the ever-increasing expectations of regulators. The only solution to close this TMF skills gap is to invest in the growth of TMF professionals through modern and dynamic TMF education.
If you are a TMF professional looking for more real-world knowledge regulatory knowledge, including how to evaluate documents like the 1572, check out our extensive library of blogs, case studies, articles, and webinars, many of the essential documents of a TMF in greater detail. If you’d like to take your individual knowledge of the TMF to the next level, visit www.tmf-u.com to learn more about TMF University and enroll today!