0670 GFI Hypertension Indication SSA 2016

Food and Drug Administration Guidance for Industry:
Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims
OMB Control Number 0910-0670
SUPPORTING STATEMENT
Terms of Clearance: None
A.

Justification

1. Circumstances Making the Collection of Information Necessary
This information collection supports Food and Drug Administration (FDA or we) guidance
regarding the labeling of drugs that include a hypertension indication. FDA has issued a
guidance document for industry entitled, “Guidance for Industry(GFI): Hypertension Indication:
Drug Labeling for Cardiovascular Outcome Claims,” that is intended to assist respondents in
developing labeling for outcome claims for drugs that are indicated to treat hypertension. With
few exceptions, current labeling for antihypertensive drugs includes only the information that
these drugs are indicated to reduce blood pressure; the labeling does not include information on
the clinical benefits related to cardiovascular outcomes expected from such blood pressure
reduction. However, blood pressure control is well established as beneficial in preventing
serious cardiovascular events, and inadequate treatment of hypertension is acknowledged as a
significant public health problem. FDA believes that the appropriate use of these drugs can be
encouraged by making the connection between lower blood pressure and improved
cardiovascular outcomes more explicit in labeling. The guidance encourages applicants to
submit labeling supplements containing the new language.
2. Purpose and Use of the Information Collection
Respondents to the collection are manufacturers of antihypertensive drugs. The guidance
provides non-binding recommendations intended to assist respondents in developing labeling for
outcome claims for drugs that are indicated to treat hypertension. The intent of the guidance is to
provide common labeling for antihypertensive drugs except where differences are clearly
supported by clinical data. The guidance encourages applicants to submit labeling supplements
containing the new language.
3. Use of Improved Information Technology and Burden Reduction
Although the guidance does not specifically prescribe the use of automated, electronic,
mechanical, or other technological collection techniques or other forms of information
technology, FDA has issued guidance documents to assist applicants in submitting information
to the agency in electronic format. These guidance documents are available at FDA's website
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection.
5. Impact on Small Businesses or Other Small Entities
The information collection applies to large and small businesses alike. FDA provides small
business and industry assistance to respondents through the Center for Drug Evaluation and
Research (CDER), available on FDA’s website at www.fda.gov.
6. Consequences of Collecting the Information Less Frequently
There is no periodic submission of information under the guidance. Recommendations are nonbinding.
7. Special Circumstances Relating to the Guidelines in 5 CFR 1320.5
There are no special circumstances for this collection of information.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the
Agency
In accordance with 5 CFR 1320.8(d), FDA published a 60 day notice soliciting public comment
in the Federal Register of February 22, 2016 (81 FR 8726). No comments were received.
9. Explanation of Any Payment or Gift to Respondents
There is no payment or gift to respondents.
10. Assurance of Confidentiality Provided to Respondents
Confidentiality of the information submitted under this guidance is protected under 21 CFR
314.430 and under 21 CFR part 20. The unauthorized use or disclosure of trade secrets required
in applications is specifically prohibited under Section 310(j) of the FD&C Act.
11. Justification for Sensitive Questions
There are no questions of a sensitive nature.
12. Estimates of Annualized Hour Burden and Costs
12a. Annualized Hour Burden Estimate
We estimate the burden for the information collection as follows:

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(1) Section IV.C of the guidance requests that the CLINICAL STUDIES section of the Full
Prescribing Information of the labeling should include a summary of placebo- or activecontrolled trials showing evidence of the specific drug’s effectiveness in lowering blood
pressure. If trials demonstrating cardiovascular outcome benefits exist, those trials also should
be summarized in this section. Table 1 in Section V of the guidance contains the specific drugs
for which the FDA has concluded that such trials exist. If there are no cardiovascular outcome
data to cite, one of the following two paragraphs should appear:
“There are no trials of [DRUGNAME] or members of the [name of pharmacologic class]
pharmacologic class demonstrating reductions in cardiovascular risk in patients with
hypertension,” or
“There are no trials of [DRUGNAME] demonstrating reductions in cardiovascular risk
in patients with hypertension, but at least one pharmacologically similar drug has
demonstrated such benefits.”
In the latter case, the applicant’s submission generally should refer to Table 1 in section V of the
guidance. If the applicant believes that Table 1 is incomplete, it should submit the clinical
evidence for the additional information to Docket No. FDA-2008-D-0150. The labeling
submission should reference the submission to the docket. FDA estimates that no more than one
submission to the docket will be made annually from one company, and that each submission
will take approximately 10 hours to prepare and submit. Concerning the recommendations for
the CLINICAL STUDIES section of the Full Prescribing Information of the labeling, FDA
regulations at 21 CFR 201.56 and 201.57 require such labeling, and the information collection
associated with these regulations is approved by OMB under OMB Control Number 0910-0572.
(2) Section VI.B of the guidance requests that the format of cardiovascular outcome
claim prior approval supplements submitted to FDA under the guidance should include the
following information:
1. A statement that the submission is a cardiovascular outcome claim supplement, with
reference to the guidance and related Docket No. FDA-2008-D-0150.
2. Applicable FDA forms (e.g., 356h, 3397).
3. Detailed Table of Contents.
4. Revised labeling:
a. Include draft revised labeling conforming to the requirements in 21 CFR 201.56
and 201.57;
b. Include marked-up copy of the latest approved labeling, showing all additions and
deletions, with annotations of where supporting data (if applicable) are located in
the submission.
In calendar years 2014 and 2015, no submissions to Docket No. FDA-2008-D-0150 were made,
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and FDA has not expended any resources in review of material related to the docket. For
purposes of this information collection approval, we are estimating that we may receive one
submission annually, and that each supplement will take approximately 20 hours to prepare and
submit. The guidance also recommends that other labeling changes (e.g., the addition of adverse
event data) should be minimized and provided in separate supplements, and that the revision of
labeling to conform to §§ 201.56 and 201.57 may require substantial revision to the ADVERSE
REACTIONS or other labeling sections.
(3) Section VI.C of the guidance states that applicants are encouraged to include the
following statement in promotional materials for the drug.
“[DRUGNAME] reduces blood pressure, which reduces the risk of fatal and nonfatal
cardiovascular events, primarily strokes and myocardial infarctions. Control of high
blood pressure should be part of comprehensive cardiovascular risk management,
including, as appropriate, lipid control, diabetes management, antithrombotic therapy,
smoking cessation, exercise, and limited sodium intake. Many patients will require more
than one drug to achieve blood pressure goals.”
The inclusion of this statement in the promotional materials for the drug would be exempt from
OMB review based on 5 CFR 1320.3(c)(2), which states that “[t]he public disclosure of
information originally supplied by the Federal government to the recipient for the purpose of
disclosure to the public is not included . . . .” within the definition of “collection of
information.”
Table 1.--Estimated Annual Reporting Burden
Activity

Number of
Respondents

Submission to Docket
Number FDA-2008-D0150
Cardiovascular Outcome
Claim Supplement
Submission
Total

Number of
Responses per
Respondent

Total Annual
Responses

Hours
Per
Response

Total
Hours

1

1

1

10

10

1

1

1

20

20
30

12b. Annualized Cost Burden Estimates
FDA estimates a cost of $2,550 for industry to submit the information collection
requested in this guidance.
Type of Respondent
NDA applicants

Total Burden Hours

Hourly Wage Rate

30

$85

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Total Respondent
Costs
$2,550

13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital Costs
There are no other capital, start-up, operating or maintenance costs associated with this
information collection.
14. Annualized Cost to the Federal Government
FDA medical officers will spend approximately 1 hour reviewing each cardiovascular outcome
claim supplement and approximately 2 hours reviewing any clinical evidence submitted to
Docket No. FDA-2008-D-0150. FDA project managers will spend about 2 hours per submission
for tracking and management tasks. Based on an hourly wage rate of $70, medical review costs
total $210 ($70 x 1 hour x 1 CV Outcome supplements; $70 x 2 hours x 1 submission to the
Docket). Based on an hourly wage rate of $40, project management costs would total $160 ($40
x 2 hours x 2 submissions). Cumulatively this results in an annual cost of $370 to the Federal
Government.
15. Explanation for Program Changes or Adjustments
As companies accomplish the objectives outlined in the guidance document, FDA expects the
information collection burden to continue to diminish. In calendar years 2014 and 2015, we did
not receive any reporting under IC 1 (submissions to Docket No. FDA-2008-D-0150) , however,
for purposes of this information collection approval, we retain our estimate that we may receive
one submission annually. Under IC 2 (cardiovascular outcome claims) we have adjusted our
estimate to reflect 19 fewer annual responses and 380 fewer annual burden hours based on
our experience with the collection since its last approval.
16. Plans for Tabulation and Publication and Project Time Schedule
There are no plans for tabulation and publication and a project time schedule.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
Display of OMB expiration date is appropriate.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

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