83 FR 52478 - Agency Information Collection Activities; Proposed Collection; Comment Request; Experimental Study of an Accelerated Approval Disclosure
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 201 (October 17, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 201 (October 17, 2018)
| Page Range | 52478-52481 | |
| FR Document | 2018-22570 |
[Federal Register Volume 83, Number 201 (Wednesday, October 17, 2018)] [Notices] [Pages 52478-52481] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-22570] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2018-N-3138] Agency Information Collection Activities; Proposed Collection; Comment Request; Experimental Study of an Accelerated Approval Disclosure AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is announcing an opportunity for public comment on the proposed collection of certain information by the Agency. Under the Paperwork Reduction Act of 1995 (PRA), Federal Agencies are required to publish notice in the Federal Register concerning each proposed collection of information and to allow 60 days for public comment in response to the notice. This notice solicits comments on research entitled ``Experimental Study of an Accelerated Approval Disclosure.'' This study will examine the presence, wording, and prominence of a disclosure communicating information related to the drug's accelerated approval in direct-to- consumer (DTC) promotional materials. DATES: Submit either electronic or written comments on the collection of information by December 17, 2018. ADDRESSES: You may submit comments as follows. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before December 17, 2018. The https://www.regulations.gov electronic filing system will accept comments until midnight Eastern Time at the end of December 17, 2018. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date. Electronic Submissions Submit electronic comments in the following way:Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your [[Page 52479]] comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov. If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ``Written/Paper Submissions'' and ``Instructions''). Written/Paper Submissions Submit written/paper submissions as follows: Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ``Instructions.'' Instructions: All submissions received must include the Docket No. FDA-2018-N-3138 for ``Experimental Study of an Accelerated Approval Disclosure'' Received comments, those filed in a timely manner (see ADDRESSES), will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday. Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ``confidential.'' Any information marked as ``confidential'' will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.thefederalregister.org/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Office of Operations, Food and Drug Administration, Three White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-7726, [email protected]. SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal Agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information set forth in this document. With respect to the following collection of information, FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology. Experimental Study of an Accelerated Approval Disclosure OMB Control Number 0910--NEW Section 1701(a)(4) of the Public Health Service Act (PHS Act) (42 U.S.C. 300u(a)(4)) authorizes FDA to conduct research relating to health information. Section 1003(d)(2)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 393(d)(2)(C)) authorizes FDA to conduct research relating to drugs and other FDA-regulated products in carrying out the provisions of the FD&C Act. The Office of Prescription Drug Promotion's (OPDP) mission is to protect the public health by helping to ensure that prescription drug information is truthful, balanced, and accurately communicated so that patients and health care providers can make informed decisions about treatment options. The OPDP's research program supports this mission by providing scientific evidence to help ensure that our policies related to prescription drug promotion will have the greatest benefit to public health. Toward that end, we have consistently conducted research to evaluate the aspects of prescription drug promotion that we believe are most central to our mission, focusing in particular on three main topic areas: Advertising features, including content and format; target populations; and research quality. Through the evaluation of advertising features we assess how elements such as graphics, format, and disease and product characteristics impact the communication and understanding of prescription drug risks and benefits; focusing on target populations allows us to evaluate how understanding of prescription drug risks and benefits may vary as a function of audience; and our focus on research quality aims at maximizing the quality of research data through analytical methodology development and investigation of sampling and response issues. This study falls under the topic of advertising features (content and format). Pursuant to section 506(c) of the FD&C Act (21 U.S.C. 356 (c)) and 21 CFR part 314, subpart H (or 21 CFR part 601, subpart E for biological products), FDA may grant accelerated approval to a drug product under section 505(c) (21 U.S.C. 355 (c)) of the FD&C Act or a [[Page 52480]] biological product under section 351(a) of the PHS Act (42 U.S.C. 262(a)). This pathway enables faster approval of prescription drugs intended to treat serious or life-threatening illnesses. Accelerated approval may be based on a determination that a drug product has an effect on a surrogate endpoint (for example, a blood test result) that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit (i.e., an intermediate clinical endpoint). In approving a drug under the accelerated approval pathway, the severity, rarity, or prevalence of a condition, and the availability or lack of alternative treatments, are taken into account. The accelerated approval pathway is limited to certain products intended to treat serious or life-threatening illnesses as there can be ``[u]ncertainty about whether clinical benefit will be verified and the possibility of undiscovered risks'' (2014 Guidance for Industry: Expedited Programs for Serious Conditions--Drugs and Biologics; available at https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf). Sponsors are generally required to conduct post approval studies to verify and describe the predicted clinical benefit, but those confirmatory studies are not complete at the time that the accelerated approval is granted (Ref. 1). In the event that the required post approval confirmatory studies fail to verify and describe the predicted effect or clinical benefit, a drug's approval can be withdrawn using expedited procedures. Under FDA's regulations governing physician labeling for prescription drugs, the INDICATIONS AND USAGE section of the FDA- approved prescribing information (PI) for a drug approved under accelerated approval must include a succinct description of the limitations of usefulness of the drug and any uncertainty about anticipated clinical benefits, with reference to the clinical studies section for a discussion of the available evidence (21 CFR 201.57(c)(2)(i)(B)). Therefore, the PI for accelerated approval products typically satisfies this requirement by including a statement in the INDICATIONS AND USAGE section about the product's approval under the accelerated approval pathway. In a draft guidance, FDA recommended that the INDICATIONS AND USAGE section for drugs approved under accelerated approval should generally describe three elements: indication(s), limitations of usefulness and clinical benefit uncertainty, and continued approval (Ref. 2). As the PI is intended for healthcare professionals, the information related to a drug's accelerated approval generally includes complex concepts and sophisticated wording. For example, PIs for accelerated approval products include language such as: This indication is approved under accelerated approval based on [surrogate endpoint]. An improvement in survival or disease- related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial; or Approval is based on a reduction in [surrogate endpoint]. There are no controlled trials demonstrating a direct treatment benefit such as improvement in disease-related symptoms, functioning, or increased survival. Despite its complexity, sponsors often use this language from the PI in DTC promotional materials for drugs approved under accelerated approval. In other cases, DTC promotion of accelerated approval products does not communicate the unique considerations and potential limitations inherent in the accelerated approval process. Disclosures may be used to communicate such information to consumers. Disclosures can include information about scientific and clinical data, any residual uncertainty about clinical benefit, and the practical utility of scientific and clinical data. These disclosures may influence consumer comprehension and affect perception of drug's risks and benefits. This study will examine the presence, wording, and prominence of a disclosure communicating information related to the drug's accelerated approval in DTC promotional materials. This information includes the use of surrogate or intermediate clinical endpoints to support approval, the uncertainty about the relationship of the surrogate or intermediate clinical endpoint to the predicted clinical benefit, and the need for confirmatory trials. We plan to conduct one pretest not longer than 20 minutes, administered via internet panel, to test the experimental manipulations and pilot the main study procedures. After implementing any lessons learned from the pilot, we then plan to conduct one main study not longer than 20 minutes, administered via internet panel. For the pretest and main study, we will randomly assign the voluntary participants to one of the test conditions (see table 1 for the study design). We have chosen to focus on oncology products because cancer is a life-threatening illness, and many oncology products are granted accelerated approval. Moreover, DTC promotion of oncology drugs is common. In the study, participants will view a website for a fictional oncology prescription drug. After viewing the website, participants will complete a questionnaire that assesses whether participants noticed the disclosure and their interpretation of it, as well as perceptions of the drug's risks and benefits. We will also measure covariates such as demographics and literacy. The questionnaire is available upon request from [email protected]. We will vary the presence and prominence of the disclosure (e.g., size, color, and location). We hypothesize that participants will be more likely to notice the disclosure when it is presented more, rather than less, prominently. In turn, we expect that participants' perceptions of the drug are more likely to be affected by the disclosure in the high prominence condition. We also will vary whether the disclosure is written in consumer-friendly language or uses language, in use by many sponsors, which is the same as or similar to that directed at healthcare professionals in FDA-approved prescription drug labeling for accelerated approval products. The consumer-friendly version of the accelerated approval disclosure will be based on consumer feedback elicited in focus groups conducted prior to the pretest (approved under OMB control number 0910-0695). The physician labeling version of the accelerated approval disclosure will be drawn from FDA-approved physician labeling. We hypothesize that participants will be more likely to notice and understand the disclosure and use it to form their perceptions of the drug if they view the consumer- friendly language. To test these hypotheses, we will conduct inferential statistical tests such as logistic regression and analysis of variance. [[Page 52481]] Table 1--Study Design ---------------------------------------------------------------------------------------------------------------- High prominence Low prominence Absent ---------------------------------------------------------------------------------------------------------------- Physician labeling version............................. Consumer-friendly version.............................. ---------------------------------------------------------------------------------------------------------------- We will recruit a general population sample of adult volunteers 18 years of age or older. We will exclude individuals who work for the U.S. Department of Health and Human Services or work in the health care, marketing, advertising, or pharmaceutical industries. We will use health literacy quotas to ensure that our sample includes participants with a range of health literacy skills. With the sample sizes described below, we will have sufficient power to detect small-sized effects in the main study (table 2). FDA estimates the burden of this collection of information as follows: Table 2--Estimated Annual Reporting Burden \1\ -------------------------------------------------------------------------------------------------------------------------------------------------------- Number of Activity Number of responses per Total annual Average burden per response Total hours respondents respondent responses -------------------------------------------------------------------------------------------------------------------------------------------------------- Pretest screener.............................. 916 1 1 0.08 (5 min.)........................... 73.28 Study screener................................ 1,507 1 1 0.08 (5 min.)........................... 120.56 Pretest....................................... 385 1 1 0.33 (20 min.).......................... 127.05 Main Study.................................... 633 1 1 0.33 (20 min.).......................... 208.89 --------------------------------------------------------------------------------------------------------- Total..................................... .............. .............. .............. ........................................ 529.78 -------------------------------------------------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. References The following references are on display at the Dockets Management Staff, Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20857, and is available for viewing by interested persons between 9 a.m. and 4 p.m., Monday through Friday; the reference marked with an asterisk is also available electronically at https://www.regulations.gov. The reference without an asterisk is not on public display at https://www.regulations.gov because it has copyright restriction, or it is available as a published article. FDA has verified the website address, as of the date this document publishes in the Federal Register, but websites are subject to change over time. 1. Beaver J.A., L.J. Howie, L. Pelosof, et al. ``A 25-Year Experience of U.S. Food and Drug Administration Accelerated Approval of Malignant Hematology and Oncology Drugs and Biologics: A Review.'' JAMA Oncology. 2018; 4(6):849-856. doi:10.1001/jamaoncol.2017.5618. 2. FDA Draft Guidance for Industry: Labeling for Human Prescription Drug and Biological Products Approved Under the Accelerated Approval Pathway (March 2014) (https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM390058.pdf). Dated: October 11, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-22570 Filed 10-16-18; 8:45 am] BILLING CODE 4164-01-P
![52478 Federal Register / Vol. 83, No. 201 / Wednesday, October 17, 2018 / Notices
www.regulations.gov and insert the exclusivity, to encourage sponsors of DEPARTMENT OF HEALTH AND
docket number, found in brackets in the investigational therapies to conduct HUMAN SERVICES
heading of this document, into the pediatric studies of medicines with the
‘‘Search’’ box and follow the prompts potential for use in children. To date, Food and Drug Administration
and/or go to the Dockets Management section 505A has been one of the few [Docket No. FDA–2018–N–3138]
Staff, 5630 Fishers Lane, Rm. 1061, mechanisms available to incentivize
Rockville, MD 20852. evaluation of new oncology products in Agency Information Collection
FOR FURTHER INFORMATION CONTACT: children and adolescents. Nevertheless, Activities; Proposed Collection;
Christine Lincoln, Center for Drug further development of more novel Comment Request; Experimental
Evaluation and Research, Food and products that address the substantial Study of an Accelerated Approval
Drug Administration, 10903 New unmet needs of the pediatric population Disclosure
Hampshire Ave. Bldg. 22, Rm. 2118, is needed.
Silver Spring, MD 20993–0002, email: AGENCY: Food and Drug Administration,
Christine.Lincoln@fda.hhs.gov. Section 504 of FDARA requires FDA, HHS.
with input from the National Cancer ACTION: Notice.
SUPPLEMENTARY INFORMATION: The use of
tumor genetic profiling in cancer Institute (NCI) and others, to develop
and regularly update: (1) A list of SUMMARY: The Food and Drug
treatment decision making has Administration (FDA, Agency, or we) is
transformed therapeutic strategies in molecular targets that are determined to
be substantially relevant to the growth announcing an opportunity for public
many adult cancers. Extension of this comment on the proposed collection of
approach to treatment decision making and progression of a pediatric cancer,
and that may trigger the requirement for certain information by the Agency.
for children with cancer, however, has Under the Paperwork Reduction Act of
been greatly diminished due to delays pediatric investigations under section
505B of the FD&C Act, and (2) a list of 1995 (PRA), Federal Agencies are
in evaluation of potentially active drugs. required to publish notice in the
Until the passage of section 504 of molecular targets of new cancer drugs
Federal Register concerning each
FDARA, section 505B of the FD&C Act and biological products in development
proposed collection of information and
(21 U.S.C. 355c) has not typically been for which the requirement for pediatric
to allow 60 days for public comment in
a useful mechanism to require the investigations under section 505B of the response to the notice. This notice
development of drugs for pediatric FD&C Act would be automatically solicits comments on research entitled
cancers, since most of the oncology waived. ‘‘Experimental Study of an Accelerated
drugs approved for adults are used to To date, a total of 205 candidate Approval Disclosure.’’ This study will
treat cancers that very rarely or never examine the presence, wording, and
molecular targets were identified from
occur in children (e.g. cancers of the prominence of a disclosure
peer-reviewed literature searches,
lung, prostate and breast). Therefore, communicating information related to
review of publicly available genomic
historically, drug sponsors have the drug’s accelerated approval in
requested and obtained waivers for databases, such as NCI Genomic Data
Commons, TARGET (Therapeutically direct-to-consumer (DTC) promotional
conducting the required assessments of materials.
these drugs in pediatric patients. Applicable Research to Generate
Additionally, drugs developed for rare Effective Targets), St. Jude PeCan Data DATES: Submit either electronic or
cancer indications that received orphan Portal, Ped PanCan, and INFORM written comments on the collection of
designation are exempted from the pre- (Individualized Therapy for Relapsed information by December 17, 2018.
FDARA requirement to conduct Malignancies in Childhood), and input ADDRESSES: You may submit comments
pediatric assessments—even if the from international subject matter as follows. Please note that late,
cancers those products are intended to experts. Of these, 62 (30.3 percent) untimely filed comments will not be
treat occur in both adult and pediatric target a gene abnormality, 40 (19.5 considered. Electronic comments must
patients—due to the fact that the orphan percent) target a cell lineage be submitted on or before December 17,
designation exempts them from such determinant, 21 (10.2 percent) target the 2018. The https://www.regulations.gov
studies (see section 505B(k) of the FD&C tumor microenvironment or the immune electronic filing system will accept
Act). However, FDARA amended system, and 77 (37.6 percent) are comments until midnight Eastern Time
section 505B so that the requirement for classified as ‘‘Others.’’ Five (2.4 percent) at the end of December 17, 2018.
pediatric investigations of drugs are candidates for automatic waivers. Comments received by mail/hand
directed at molecular targets determined delivery/courier (for written/paper
Dated: October 11, 2018.
to be substantially relevant to the submissions) will be considered timely
growth and progression of a pediatric Leslie Kux, if they are postmarked or the delivery
cancer apply even when the adult Associate Commissioner for Policy. service acceptance receipt is on or
indication has received an orphan [FR Doc. 2018–22565 Filed 10–16–18; 8:45 am] before that date.
designation, or when the adult BILLING CODE 4164–01–P
Electronic Submissions
indication does not occur, in the
pediatric population (e.g., prostate Submit electronic comments in the
cancer). following way:
Although requirements to study • Federal eRulemaking Portal:
investigational therapies in pediatric https://www.regulations.gov. Follow the
daltland on DSKBBV9HB2PROD with NOTICES
oncology were exceedingly rare, other instructions for submitting comments.
incentives have been put into place to Comments submitted electronically,
promote the development of oncology including attachments, to https://
products for pediatric cancer. Section www.regulations.gov will be posted to
505A of the FD&C Act (21 U.S.C. 355a) the docket unchanged. Because your
provides incentives, in the form of 6 comment will be made public, you are
months of additional marketing solely responsible for ensuring that your
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![52480 Federal Register / Vol. 83, No. 201 / Wednesday, October 17, 2018 / Notices
biological product under section 351(a) recommended that the INDICATIONS the main study procedures. After
of the PHS Act (42 U.S.C. 262(a)). This AND USAGE section for drugs approved implementing any lessons learned from
pathway enables faster approval of under accelerated approval should the pilot, we then plan to conduct one
prescription drugs intended to treat generally describe three elements: main study not longer than 20 minutes,
serious or life-threatening illnesses. indication(s), limitations of usefulness administered via internet panel. For the
Accelerated approval may be based on and clinical benefit uncertainty, and pretest and main study, we will
a determination that a drug product has continued approval (Ref. 2). As the PI is randomly assign the voluntary
an effect on a surrogate endpoint (for intended for healthcare professionals, participants to one of the test conditions
example, a blood test result) that is the information related to a drug’s (see table 1 for the study design). We
reasonably likely to predict clinical accelerated approval generally includes have chosen to focus on oncology
benefit, or on a clinical endpoint that complex concepts and sophisticated products because cancer is a life-
can be measured earlier than wording. For example, PIs for threatening illness, and many oncology
irreversible morbidity or mortality, that accelerated approval products include products are granted accelerated
is reasonably likely to predict an effect language such as: approval. Moreover, DTC promotion of
on irreversible morbidity or mortality or • This indication is approved under oncology drugs is common. In the study,
other clinical benefit (i.e., an accelerated approval based on [surrogate participants will view a website for a
intermediate clinical endpoint). In endpoint]. An improvement in survival fictional oncology prescription drug.
approving a drug under the accelerated or disease-related symptoms has not After viewing the website, participants
approval pathway, the severity, rarity, been established. Continued approval will complete a questionnaire that
or prevalence of a condition, and the for this indication may be contingent assesses whether participants noticed
availability or lack of alternative upon verification and description of the disclosure and their interpretation of
treatments, are taken into account. clinical benefit in the confirmatory trial; it, as well as perceptions of the drug’s
The accelerated approval pathway is or risks and benefits. We will also measure
limited to certain products intended to • Approval is based on a reduction in covariates such as demographics and
treat serious or life-threatening illnesses [surrogate endpoint]. There are no literacy. The questionnaire is available
as there can be ‘‘[u]ncertainty about controlled trials demonstrating a direct upon request from DTCresearch@
whether clinical benefit will be verified treatment benefit such as improvement fda.hhs.gov.
and the possibility of undiscovered in disease-related symptoms,
risks’’ (2014 Guidance for Industry: functioning, or increased survival. We will vary the presence and
Expedited Programs for Serious Despite its complexity, sponsors often prominence of the disclosure (e.g., size,
Conditions—Drugs and Biologics; use this language from the PI in DTC color, and location). We hypothesize
available at https://www.fda.gov/ promotional materials for drugs that participants will be more likely to
downloads/Drugs/Guidances/ approved under accelerated approval. In notice the disclosure when it is
UCM358301.pdf). Sponsors are other cases, DTC promotion of presented more, rather than less,
generally required to conduct post accelerated approval products does not prominently. In turn, we expect that
approval studies to verify and describe communicate the unique considerations participants’ perceptions of the drug are
the predicted clinical benefit, but those and potential limitations inherent in the more likely to be affected by the
confirmatory studies are not complete at accelerated approval process. disclosure in the high prominence
the time that the accelerated approval is Disclosures may be used to condition. We also will vary whether
granted (Ref. 1). In the event that the communicate such information to the disclosure is written in consumer-
required post approval confirmatory consumers. Disclosures can include friendly language or uses language, in
studies fail to verify and describe the information about scientific and clinical use by many sponsors, which is the
predicted effect or clinical benefit, a data, any residual uncertainty about same as or similar to that directed at
drug’s approval can be withdrawn using clinical benefit, and the practical utility healthcare professionals in FDA-
expedited procedures. of scientific and clinical data. These approved prescription drug labeling for
Under FDA’s regulations governing disclosures may influence consumer accelerated approval products. The
physician labeling for prescription comprehension and affect perception of consumer-friendly version of the
drugs, the INDICATIONS AND USAGE drug’s risks and benefits. This study accelerated approval disclosure will be
section of the FDA-approved prescribing will examine the presence, wording, based on consumer feedback elicited in
information (PI) for a drug approved and prominence of a disclosure focus groups conducted prior to the
under accelerated approval must communicating information related to pretest (approved under OMB control
include a succinct description of the the drug’s accelerated approval in DTC number 0910–0695). The physician
limitations of usefulness of the drug and promotional materials. This information labeling version of the accelerated
any uncertainty about anticipated includes the use of surrogate or approval disclosure will be drawn from
clinical benefits, with reference to the intermediate clinical endpoints to FDA-approved physician labeling. We
clinical studies section for a discussion support approval, the uncertainty about hypothesize that participants will be
of the available evidence (21 CFR the relationship of the surrogate or more likely to notice and understand
201.57(c)(2)(i)(B)). Therefore, the PI for intermediate clinical endpoint to the the disclosure and use it to form their
accelerated approval products typically predicted clinical benefit, and the need perceptions of the drug if they view the
satisfies this requirement by including a for confirmatory trials. consumer-friendly language. To test
statement in the INDICATIONS AND We plan to conduct one pretest not these hypotheses, we will conduct
USAGE section about the product’s longer than 20 minutes, administered inferential statistical tests such as
daltland on DSKBBV9HB2PROD with NOTICES
approval under the accelerated approval via internet panel, to test the logistic regression and analysis of
pathway. In a draft guidance, FDA experimental manipulations and pilot variance.
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![Federal Register / Vol. 83, No. 201 / Wednesday, October 17, 2018 / Notices 52481
TABLE 1—STUDY DESIGN
High prominence Low prominence Absent
Physician labeling version.
Consumer-friendly version.
We will recruit a general population marketing, advertising, or have sufficient power to detect small-
sample of adult volunteers 18 years of pharmaceutical industries. We will use sized effects in the main study (table 2).
age or older. We will exclude health literacy quotas to ensure that our FDA estimates the burden of this
individuals who work for the U.S. sample includes participants with a collection of information as follows:
Department of Health and Human range of health literacy skills. With the
Services or work in the health care, sample sizes described below, we will
TABLE 2—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of Average
Number of Total annual Total
Activity responses per burden per
respondents responses hours
respondent response
Pretest screener ........................................................... 916 1 1 0.08 (5 min.) ......... 73.28
Study screener ............................................................. 1,507 1 1 0.08 (5 min.) ......... 120.56
Pretest .......................................................................... 385 1 1 0.33 (20 min.) ....... 127.05
Main Study ................................................................... 633 1 1 0.33 (20 min.) ....... 208.89
Total ...................................................................... ........................ ........................ ........................ ............................... 529.78
1 There are no capital costs or operating and maintenance costs associated with this collection of information.
References Dated: October 11, 2018. Furthermore, any interested person may
Leslie Kux, petition FDA for a determination
The following references are on Associate Commissioner for Policy. regarding whether the applicant for
display at the Dockets Management [FR Doc. 2018–22570 Filed 10–16–18; 8:45 am] extension acted with due diligence
Staff, Food and Drug Administration, during the regulatory review period by
BILLING CODE 4164–01–P
5630 Fishers Lane, Rm. 1061, Rockville, April 15, 2019. See ‘‘Petitions’’ in the
MD 20857, and is available for viewing SUPPLEMENTARY INFORMATION section for
by interested persons between 9 a.m. DEPARTMENT OF HEALTH AND more information.
and 4 p.m., Monday through Friday; the HUMAN SERVICES ADDRESSES: You may submit comments
reference marked with an asterisk is also as follows. Please note that late,
available electronically at https:// Food and Drug Administration untimely filed comments will not be
www.regulations.gov. The reference [Docket No. FDA–2017–E–6541] considered. Electronic comments must
without an asterisk is not on public be submitted on or before December 17,
display at https://www.regulations.gov Determination of Regulatory Review 2018. The https://www.regulations.gov
because it has copyright restriction, or it Period for Purposes of Patent electronic filing system will accept
is available as a published article. FDA Extension; DUPIXENT comments until 11:59 p.m. Eastern Time
has verified the website address, as of at the end of December 17, 2018.
AGENCY: Food and Drug Administration, Comments received by mail/hand
the date this document publishes in the HHS.
Federal Register, but websites are delivery/courier (for written/paper
ACTION: Notice. submissions) will be considered timely
subject to change over time.
if they are postmarked or the delivery
1. Beaver J.A., L.J. Howie, L. Pelosof, et SUMMARY: The Food and Drug
service acceptance receipt is on or
al. ‘‘A 25-Year Experience of U.S. Administration (FDA or the Agency) has before that date.
Food and Drug Administration determined the regulatory review period
for DUPIXENT and is publishing this Electronic Submissions
Accelerated Approval of Malignant
Hematology and Oncology Drugs notice of that determination as required Submit electronic comments in the
by law. FDA has made the following way:
and Biologics: A Review.’’ JAMA
Oncology. 2018; 4(6):849–856.
determination because of the • Federal eRulemaking Portal:
submission of an application to the https://www.regulations.gov. Follow the
doi:10.1001/jamaoncol.2017.5618.
Director of the U.S. Patent and instructions for submitting comments.
2. FDA Draft Guidance for Industry: Trademark Office (USPTO), Department Comments submitted electronically,
Labeling for Human Prescription of Commerce, for the extension of a including attachments, to https://
Drug and Biological Products patent which claims that human www.regulations.gov will be posted to
daltland on DSKBBV9HB2PROD with NOTICES
Approved Under the Accelerated biological product. the docket unchanged. Because your
Approval Pathway (March 2014) DATES: Anyone with knowledge that any comment will be made public, you are
(https://www.fda.gov/downloads/ of the dates as published (see the solely responsible for ensuring that your
Drugs/GuidanceCompliance SUPPLEMENTARY INFORMATION section) are comment does not include any
RegulatoryInformation/Guidances/ incorrect may submit either electronic confidential information that you or a
UCM390058.pdf). or written comments and ask for a third party may not wish to be posted,
redetermination by December 17, 2018. such as medical information, your or
VerDate Sep<11>2014 19:46 Oct 16, 2018 Jkt 247001 PO 00000 Frm 00106 Fmt 4703 Sfmt 4703 E:\FR\FM\17OCN1.SGM 17OCN1](https://thefederalregister.org/doc/83_FR_52679/page/4.svg)
Document Created: 2018-10-17 01:47:17
Document Modified: 2018-10-17 01:47:17
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice. | |
| Dates | Submit either electronic or written comments on the collection of information by December 17, 2018. | |
| Contact | Ila S. Mizrachi, Office of Operations, Food and Drug Administration, Three White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-7726, [email protected] | |
| FR Citation | 83 FR 52478 |
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