Earlier this week the Department of Health and Human Services (“HHS”) published its long awaited notice of proposed rulemaking regarding the registration of clinical trials.  The most significant change that would result from implementation of the proposed rule, and the one getting the most press, is the new requirement that results data be submitted for all applicable clinical trials, even those evaluating unapproved drugs and devices.   Although we agree that this new requirement is likely to have significant ramifications for drug, biologic and device manufacturers, here are five other issues you may want to focus on as you review the proposed rule:

1.   All combination product clinical trials will be considered drug clinical trials regardless of the product’s primary mode of action. 

This will have a significant impact on clinical trials involving unapproved or uncleared combination products that are subject to FDA regulation as medical devices.  Because these clinical trials will be considered drug clinical trials, NIH will publish the full registration information within 30 days of the information being submitted.  However, if these clinical trials were regulated as device clinical trials, the majority of the registration information would not be published until the combination product was approved or cleared.

2.   The bright line rule between a clinical trial evaluating a new use of an approved, cleared or licensed product and a clinical trial evaluating a new product that is unapproved, unlicensed or uncleared is not so bright.

The determination of which side of the line a clinical trial sits on will depend on the type of submission the clinical trial is intended to support.  If the clinical trial is intended to support a new application (i.e., NDA, ANDA, BLA, PMA) or premarket notification (i.e., 510(k)) for a new product, the clinical trial is evaluating a new product under the proposed rule.  However, if it is intended to support a supplement or a 510(k) for a new indication, then it is evaluating a new use.

Not only is it unclear how a manufacturer is supposed to parse whether a 510(k) is for a new indication or for a new device, but the “application = new product; supplement = new use” formula suggested by the proposed rule is not always applicable to approved devices.  Current FDA guidance states that, at least, certain changes to an approved device’s indications for use require the submission of a new PMA.  Additionally, the proposed rule fails to explain whether a clinical trial evaluating an unapproved or uncleared combination product would be considered a clinical trial of a new product if one of the constituent parts was previously approved or cleared.

As this distinction plays an important role the ability of a sponsor to delay reporting the results of a clinical trial, this could be a significant issue requiring clarification.

3.   The length of time a sponsor can delay publication of results is the same regardless of whether the clinical trial evaluates the new use of an approved, cleared or licensed product or it evaluates a new product.

The length of time sponsors can delay submission of clinical trial results is subject to statutory limitations with respect to clinical trials evaluating the new use of an approved or cleared product (i.e., up to two years following submission of notice certifying qualification for delayed publication).  The same is not true for clinical trials evaluating the use of a new product.  Yet, HHS decided to impose the same limitation after determining that the benefits of publication outweighed the potential competitive disadvantages this may cause to manufacturers that are developing new products.

4.   HHS found a creative way around the requirement that it not publish most applicable device clinical trial registration information prior to approval or clearance of the device.

By requiring results data from all applicable device trials to be submitted regardless of whether the clinical trial evaluated an unapproved or uncleared medical device, HHS created the problem that results data could be published before it is permitted to publish the registration information for the clinical trial.  Recognizing the results data would be of little value without the accompanying registration information, HHS got creative. 

Instead of “publishing the registration data” HHS now requires the submission of the same information provided in the registration as part of the results data from these clinical trials.  However, to avoid repetitive data entry, HHS permits sponsors to certify to certify that the same information included in the registration information has been verified and updated, and is ready to be posted along with the results.

Device manufacturers may want to consider using the need for this creative work around to support comments requesting the ability to delay submission of results from clinical trials evaluating unapproved or uncleared devices.

5.   HHS has imposed additional requirements regarding the frequency at which submitted data must be corrected or updated.

The proposed rule expands the number of data elements, from two to ten, that must be updated within 30 days of the sponsor becoming aware of the need to update the data.  Additionally, the proposed rule requires sponsors to update data within 15 days in the event it becomes aware, either on its own or upon notification by NIH, of errors in the data.  Sponsors may want to consider whether these timing requirements are too burdensome or are impracticable. 

It is important to note that these deadlines apply to data updates and error corrections regardless of whether the original data was required to be submitted because it relates to an applicable clinical trial or the data was voluntarily submitted. 

In light of this and other obligations imposed on sponsors who voluntarily submit data, it is important to consider whether these obligations are likely to discourage sponsors from voluntary submitting information about, and reporting results from, clinical trials that are not applicable clinical trials.

HHS is accepting comments on the proposed rule, through February 19, 2015. 

* I would like to thank Ryan Benz, Shilpa Prem and Bonnie Scott for their help in reviewing and analyzing the proposed rule.