Updates to 1572 Guidance

The FDA has finally released a final FAQ, representing their 'current thinking' on 1572s.  The guidance in the form of question and answer runs for 17 pages and covers, among other things, how to fill it out, who should be listed in item #6, whether it is required to be submitted to the FDA, and under what circumstances an investigator needs to sign a new one.  Makes for surprisingly interesting reading. 

In this FAQ the 1572 is describes as having two purposes: one) to provide the sponsor with information about the investigator's qualifications and the suitability of the site for clinical trial purposes, and two) tho inform the investigator of his/her obligations and to obtain the investigator's commitment to discharge those obligations according to the regulations.  This clearly defines the document as a two-way communication tool in addition to a statement of undertaking.  The parties involved in the communication flow are the sponsor and the investigator.  Notice that the FDA is not among those sharing in this conversation.  The guidance makes it clear that sponsors are not required to submit the 1572 to the IND, although it acknowledges that most sponsors do because it is a convenient collection tool for all the information that sponsors must submit to the FDA under 21 CFR 312.23(a)(6)(iii)(b).  This is a small but potentially important distinction:  the 1572 itself is not required to be submitted, just the information contained.  A sponsor could submit that information on a separate sheet of paper and be fully in compliance.  Most regulatory folks both of sponsors and CROs have always insisted that the 1572 itself must be submitted, yet I never found a regulations supporting the policy.  It's nice to know what the requirement actually is.

Study Coordinators Now Should be Listed Routinely

Former FDAer and blogger Carl Anderson has an excellent run-down on one of the other new provisions of the guidance, namely that study coordinators should now be listed on the 1572:

“Generally, a research coordinator has a greater role in performing critical study functions and making direct and significant contributions to the study data. For example, a research coordinator often recruits subjects, collects and evaluates study data, and maintains study records. Therefore, the research coordinator should usually be listed in Section #6 of the 1572.”

This represents a major shift from the draft 1572 guidance dated July 2008, where it was recommended that study coordinators be listed if performing "critical study functions".   The change appears to acknowledge not only that study coordinators play a consistently critical role in study conduct, but also that they take a significant role in recruiting subjects.

Notice also the non-committal use of words like "should" and "generally", but don't be mistaken:  The FDA considers their guidances and FAQ's to be a close to regulation as you can get without going through the full process, so as Carl says, might be a good idea to update your 1572s to include study coordinators.

Sign It Once and Done

 
However after you get all your 1572s updated to reflect this guidance, the FDA says you shouldn't be revising them and having the investigator re-sign them any time something changes during a study, like new sub-investigators or a change in lab.  The guidance says that 1572 needs to be completed and signed by the principal investigator on only two occasions:  when participating in a new protocol under the IND or when he is being added to an existing protocol under an IND (question 7, page 6).  One hopes that this will cut down on some of the paper chase that goes on throughout long studies when people think they have to update the 1572 every time some item on it changes.  The FDA says we can simply include these changes during routine informational updates to the IND.

Use of Foreign Investigators
 
The FAQ also has a lot of guidance on the requirements of foreign investigators vis-a-vis the 1572, use of foreign data in support of submissions, foreign investigators obligations with respect to local versus US laws, and so one.  I did not know for example that multinational studies may include domestic sites under the IND and foreign sites not under the IND.  In that case the non-US investigators would not be required to sign the 1572, which is sometimes a sticking point with them as they don't wish to be obligated to US law, and the sponsor could use similar rather than exactly identical protocols to allow for differences in medical practice yet still result in pool-able data.  If this is a change it is a good one.

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How about a photo?   Here is one from a recent project management workshop that we led in Bombay.

It was mango season.