[Federal Register Volume 78, Number 107 (Tuesday, June 4, 2013)]
[Pages 33421-33423]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-13083]



Food and Drug Administration

[Docket No. FDA-2013-N-0271]

Availability of Masked and De-identified Non-Summary Safety and 
Efficacy Data; Request for Comments

ACTION: Notice; request for comments.


AGENCY: Food and Drug Administration, HHS.
SUMMARY: The Food and Drug Administration (FDA) is seeking public 
comments from interested persons on the proposed availability of de-
identified and masked data derived from medical product applications. 
Improving the efficiency and

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effectiveness of medical product development is a national priority. 
The ability to make available de-identified and masked clinical and 
preclinical data derived from marketing applications could make an 
important contribution to that goal by providing scientific data that 
may be of value in the generation of new knowledge to facilitate 
innovation in the development and evaluation of critically needed 
medical products. The contribution of patients who participate in 
clinical trials should be maximized for the benefit of society. The 
Agency invites comments on the issues to be considered with regard to 
such availability and on any limitations that should be placed on the 
availability of these data.

DATES: Submit either electronic or written comments by August 5, 2013.

ADDRESSES: Submit electronic comments to http://www.regulations.gov. 
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. All comments should be identified with the docket 
number found in brackets at the heading of this document.

Evaluation and Research, Food and Drug Administration, 10001 New 
Hampshire Ave., HILL-3110, Silver Spring, MD 20993, 301-796-3603, FAX: 
301-431-6351, [email protected]; or Stephen Ripley, Center for 
Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-
1448, 301-827-6210; or Aaliyah Eaves-Leanos, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, rm. 5435, 301-796-2948, FAX: 301-847-8510. 
[email protected].


I. Background

    Commissioner of Food and Drugs Margaret Hamburg has emphasized 
FDA's role as a public health Agency (Ref. 1). In accordance with its 
responsibility to promote the public health, FDA has, in collaboration 
with the National Institutes of Health, launched the Regulatory Science 
Initiative, a call to action to enhance the science and knowledge 
critical to improving the development, manufacture, evaluation, and 
safe use of critically needed new therapies. In addition, the Food and 
Drug Administration Safety and Innovation Act (FDASIA), enacted on July 
9, 2012, contains important new authorities that will enhance the 
Agency's ability to promote innovation across industry, research and 
clinical care settings, including new provisions that require the 
development of a plan for advancing regulatory science for medical 
products in order to promote the public health and advance innovation 
in regulatory decision making. (See, e.g., section 1124 of FDASIA (Pub. 
L. 112-144).)
    The development of new knowledge and insights from clinical and 
preclinical study data is an important regulatory science opportunity. 
These data have a tremendous potential to help address critical 
challenges and provide new opportunities for innovation in medical 
product development, including for human drugs, medical devices, and 
biological products. Safety and effectiveness data from multiple 
studies have been used in the past to address key hurdles in drug 
development. Analysis of data from multiple clinical and preclinical 
studies has been used to identify potentially valid endpoints for 
clinical trials, understand the predictive value of preclinical models, 
clarify how medical products work in different diseases, and inform 
development of novel clinical designs and endpoints to the benefit of 
    For example, the primary endpoint for chronic hepatitis C trials 
has been based on detection of hepatitis C virus at week 24 of follow 
up. Evidence suggested that assessing the response at earlier follow up 
time points may provide an equivalent measurement of drug response. FDA 
scientists conducted an analysis of the combined data from 15 clinical 
trials and 3 pediatric trials from 5 drug development programs to 
determine whether assessments conducted at earlier time points could 
provide results that were predictive of the outcomes at 24 weeks of 
follow up (Ref. 2). The sustained virologic response measurements at 12 
and 24 weeks of follow up were concordant across a large population 
database involving multiple trials, viral genotypes, treatment 
regimens, and durations. The sustained virologic response at 12 weeks 
of follow up was determined to be suitable as a primary endpoint in 
clinical trials and allows for hepatitis C virus treatment options to 
be available earlier for patients suffering from this disease. The 
sustained virologic response at 4 weeks of follow up may have utility 
in guiding dose and treatment strategies when designing registration 
trials. The use of earlier time points for key regulatory decisions and 
dose selection may facilitate drug development for additional 
therapeutics under investigation.
    In addition to identification of additional endpoints for clinical 
studies, pooled data (both preclinical and clinical) have also been 
applied to the analysis of safety issues. An analysis of 199 clinical 
trials of 11 antiepileptic drugs by FDA helped quantify the increased 
risk of suicidal behavior or ideation for patients and prescribers. 
(Statistical Review and Evaluation: Antiepileptic Drugs and Suicidality 
(May 23, 2008): http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM192556.pdf.) 
An independent analysis of data on 5 potential biomarkers of kidney 
injury by the Predictive Safety Testing Consortium led to their 
qualification for inclusion in pre-clinical safety data submissions 
(Ref. 3). These markers are now being evaluated for their utility as 
more sensitive markers of early kidney damage in human clinical trials. 
Thus, advances in regulatory science can arise from analysis of diverse 
data submitted as part of marketing applications, including, for 
example data related to clinical outcomes, safety, biomarker status, 
drug disposition, drug action, or patient reported outcomes. (See, 
e.g., 21 CFR 314.50 (specifying the content of new drug applications).)
    FDA has considerable expertise in analyzing individual patient 
level and aggregated clinical trial data, but recognizes the potential 
to further advance regulatory science by allowing other experts the 
opportunity to contribute to these efforts. To fully realize the 
potential of these data, experts outside of FDA would need to become 
actively engaged in the research. FDA is considering approaches to 
providing access by non-FDA experts and other interested parties to 
data that have research value in a way that would both safeguard the 
privacy interests of patients enrolled in clinical trials, and 
appropriately protect the commercial investments of sponsors.
    Consistent with and in furtherance of the objectives and mission of 
Commissioner Hamburg's Transparency Initiative, FDA intends to consider 
the extent and nature of public availability of de-identified and 
masked subject level data necessary to achieve specific aims. For more 
information on the Transparency Initiative, see http://www.fda.gov/AboutFDA/Transparency/TransparencyInitiative/default.htm.
    FDA uses the term ``masked data'' in this notice to refer to data 
with information removed that could link it to a specific product or 
application. The Agency will consider different strategies

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to minimize the ability to identify specific products and the impact of 
any such strategies. Such strategies might include making available 
certain data from a random sample or appropriately chosen subset of 
subjects, restricting the data fields made available or pooling data 
where possible from studies of multiple members of a product class, 
without identifying the specific product.
    For the purposes of this notice, de-identified data refers to data 
that does not identify an individual and with respect to which there is 
no reasonable basis to believe that the information can be used to 
identify an individual. Cf. 45 CFR 164.514(a) (although FDA references 
the standard used in the Privacy Rule here, the Agency notes that it is 
not a covered entity for the purposes of that Rule). The Agency has an 
unwavering commitment to protecting the privacy of research subjects' 
identities. As such, consistent with FDA's regulations at 21 CFR 
20.63(a), any data that might be made available under this proposal 
would be stripped of any information which could identify patients or 
research subjects, either directly or through combination with other 
publicly available information. See id. (``The names and other 
information which would identify patients or research subjects . . . 
shall be deleted before the record is made available for public 
disclosure.'') This same regulation also directs outside parties to 
remove such personal identifiers from records prior to submission to 
FDA. (See Sec.  20.63(b).)
    De-identified and masked data could be used to advance public 
health. For example, a model of disease progression in control arms of 
future studies could be based on pooled control group data from past 
studies of the same disease or indication and would not require 
identification of a product or even product class nor would there be 
personal identifiers associated with the data. Similarly, 
characterization of risk factors might only involve control group data. 
On the other hand, validating a biomarker as a surrogate for a clinical 
outcome or as a predictive classifier of potential treatment response 
might require identification of products by class or analysis across a 
class to show consistency.
    We note that this proposal contemplates the availability of certain 
data after appropriate steps have been taken to de-identify it and 
remove the data's link to a specific product, study, or application. 
This proposal does not pertain to unmasked safety and effectiveness 
data, (i.e., data that can be linked to a specific, identified 
application) including full study reports; the circumstances under 
which this information is disclosed is already specifically set forth 
in the Federal Food Drug and Cosmetic Act and FDA's regulations. 
Further, FDA will not make available business-related confidential 
commercial information contained in product applications, including but 
not limited to information concerning licensing agreements and 
information identifying suppliers, unless such information has already 
been publicly disclosed by the sponsor. Nor will the Agency make 
available trade secret information under this proposal. Such 
information will continue to be treated in a manner consistent with 
sections 301(j), 505(l), 520(c), 535(d), and 537(e) of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 331(j), 351(l), 360j(c), 
360ll(d), and 360nn); the Trade Secrets Act (18 U.S.C. 1905); and FDA's 
regulations (21 CFR 20.61, 314.430, 601.51, and 814.9).

II. Request for Comments

    FDA is interested in receiving comments from the public on the 
following topics: (1) What factors should be considered in masking 
study data (e.g., data fields from regulatory submissions to remove or 
modify, number of different products to pool within a product class), 
(2) what limitations, if any, should there be on the Agency's ability 
to make available the masked data as described previously, (3) are 
there any additional factors FDA should consider in de-identifying data 
in addition to FDA's requirement to remove any names and other 
information (e.g., birth date, death date, local geographic 
information, contact information) which would identify patients or 
research subjects before disclosing information, (4) would regulatory 
changes facilitate implementation of such a proposal, and if so, what 
changes would be most useful, and (5) which situations do you believe 
disclosing masked data would be most useful to advance public health?
    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify the question your comment addresses 
by the number assigned to that question. Identify comments with the 
docket number found in brackets in the heading of this document. 
Received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to 
the docket at http://www.regulations.gov.

III. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and are available electronically at http://www.regulations.gov. (FDA 
has verified all the Web site addresses in this reference section, but 
we are not responsible for any subsequent changes to the Web sites 
after this document publishes in the Federal Register.)

    1. Hamburg, M. A. and J. M. Sharfstein, ``The FDA as a Public 
Health Agency,'' New England Journal of Medicine, 2009 June 11; 
    2. Chen J., J. Florian, W. Carter, et al. ``Earlier Sustained 
Virologic Response End Points for Regulatory Approval and Dose 
Selection of Hepatitis C Therapies.'' Gastroenterology, 2013 March 4 
    3. Dieterle, F., et al., ``Renal Biomarker Qualification 
Submission: A Dialog Between the FDA-EMEA and Predictive Safety 
Testing Consortium,'' Nature Biotechnology, 2010 May; 28(5):455-62.

    Dated: May 29, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-13083 Filed 6-3-13; 8:45 am]