Federal Register/Vol. 63, No. 216/Monday, November 9, 1998/Notices 60353
DEPARTMENT OF HEALTH AND could be reviewed by the IRB through them at risk of criminal or civil liability
HUMAN SERVICES the expedited review procedures set or be damaging to the subjects financial
forth in the FDAs regulations. OPRR standing, employability, insurability,
Food and Drug Administration has a separate codification that reputation, or be stigmatizing, unless
references the Expedited Review List for reasonable and appropriate protections
[Docket No. 97N0447]
matters under the Department of Health will be implemented so that risks
Protection of Human Subjects: and Human Services (HHS) jurisdiction related to invasion of privacy and
Categories of Research That May Be (45 CFR part 46). The HHS list was breach of confidentiality are no greater
published in the Federal Register on than minimal. At the time of the
Reviewed by the Institutional Review
January 26, 1981 (46 FR 8392). The FDA publication of the 1981 list, FDA
Board (IRB) Through an Expedited
and HHS lists published in 1981 differ routinely considered only the medical
Review Procedure
slightly, in that item nine on the HHS risk to subjects in determining whether
AGENCY: Food and Drug Administration, list, concerning research on individual a study imparted greater than minimal
HHS. or group behavior, pertains only to 45 risk. Since that time, the scope of
ACTION: Notice. CFR 46.110. Because behavioral research projects that are under FDA
research is not specifically regulated by purview has expanded to include
SUMMARY: On November 10, 1997, the FDA, that category was not included in activities that could place the subjects at
Food and Drug Administration (FDA), the list published by FDA. risk for the harms listed in paragraph
in consultation with the Office for The comments received in response to (C). Therefore, the IRBs reviewing
Protection from Research Risks (OPRR) the November 10, 1997 (62 FR 60607), studies of FDA regulated products may
at the National Institutes of Health, proposal by FDA and OPRR to revise the need to consider the listed nonmedical
requested written comments relating to 1981 expedited review list harms. For certain studies subject to
the proposed republication of the list overwhelmingly supported the regulation under 45 CFR part 46, these
that identifies certain research activities proposed revision of the list. Three concerns have always been implicit in
involving human subjects that may be comments indicated that there should determining whether an activity is a
reviewed by the Institutional Review be no expedited review available at all. minimal risk activity. The words
Board (IRB) through the expedited These comments misunderstood the insurability and be stigmatizing
review procedure authorized in 21 CFR purpose of expedited review, expressing have been added to the new list to help
56.110. The comment period closed on concern that allowing expedited IRB ensure that the IRBs consider these
March 10, 1998. FDA and OPRR review also removes the requirement for potential risks during their review.
received a combined total of 108 informed consent of study subjects. FDA Two comments point out that
comments. After a review of the and OPRR disagree with these three classified research must be reviewed by
comments, FDA and OPRR are now comments and believe that expedited the IRB at a convened meeting. FDA and
simultaneously publishing identical review is an appropriate part of the IRB OPRR agree and have added paragraph
revised lists of categories of research review process. In addition, deleting the (D), which prohibits expedited review
activities that may be reviewed by the expedited review process would require for classified research involving human
IRB through the expedited review a regulatory change to section 110 of the subjects. This is in accordance with the
procedure. Federal Policy, which is beyond the March 27, 1997, Presidential
scope of this revision. However, in memorandum that proposed the
EFFECTIVEDATE: The revised list is
response to these comments paragraph elimination of an expedited review
effective November 9, 1998.
(E) has been added to the Applicability procedure for all classified research
FORFURTHERINFORMATIONCONTACT: Paul
section I of this document to make it involving human subjects.
W. Goebel, Jr., Office of Health Affairs
clear that the standard requirements for Paragraph (E) serves as a reminder to
(HFY20), Food and Drug
informed consent must be met the IRBs that informed consent and
Administration, 5600 Fishers Lane,
regardless of the type of review expedited review are two totally
Rockville, MD 20857, 3018271685.
expedited or convenedutilized by the separate issues. This responds to
SUPPLEMENTARYINFORMATION: The FDA IRB. concerns that allowing an increase in
regulations for protection of human The following discussion summarizes the scope of research eligible for
subjects can be found under part 50 (21 the 108 comments received and the expedited review would result in more
CFR part 50), and the regulations for the resulting changes. In response to over 40 waivers of informed consent. Research
IRBs can be found under part 56 (21 comments expressing concern that the reviewed under the expedited review
CFR part 56). The regulations require, general principles that apply to all procedure is not necessarily eligible for
with limited exceptions, obtaining and research categories could be easily waiver or alteration of informed
documenting legally effective informed misinterpreted, the introductory consent. All research, regardless of
consent for all human subjects of paragraph to the 1981 list has been whether it meets the conditions for
research on FDA regulated products and reformatted into six general principles expedited IRB review, must conform to
review of research involving human that apply to the entire list. The the applicable requirements for
subjects by an IRB. parenthetical in the introductory obtaining and documenting informed
Section 56.110 provides for expedited sentence to the 1981 list (carried out consent. Informed consent must be
IRB review procedures for certain through standard methods) has been obtained and documented unless the
categories of research involving no more deleted in response to comments that research meets one of the conditions for
than minimal risk, and for minor this phrase served no particular purpose waiving, excepting, or otherwise
changes in previously approved in the 1981 list. altering the informed consent
research during the period for which The reformatted general principles are requirements that are set forth in 45 CFR
approval is authorized. The list that is set forth in paragraphs (A) through (G). 46.116 and 46.117, and 50.23, 50.24,
referenced in 56.110(a) was originally Paragraph (C) makes it clear that the IRB and 56.109(c).
published in the Federal Register of must consider, for all categories, The list of research eligible for
January 27, 1981 (46 FR 8980), as a whether identification of the subjects or expedited review continues to fall into
notice of a list of research activities that their responses would reasonably place nine categories. Category one, 60354 Federal Register/Vol. 63, No. 216/Monday, November 9, 1998/Notices
enumerated as category nine on the collection of biological specimens. voice, video, digital, or image
1981 list, addresses the availability of Some of the comments requested recordings. In the proposal, the IRB was
expedited review for marketed drugs inclusion of specific procedures, such as to consider certain risks to the subjects
and devices. This category now contains throat cultures and pap smears. Some of in this category before granting
citations to the investigational drug and the comments requested the category be expedited review. In response to several
device regulations and provides when rephrased as a general limit, setting out comments that inquired why only this
expedited review of research on as examples the types of specimens and type of research should receive this
marketed drugs (including biologics) conditions for collection. In response to consideration, it was incorporated as a
would not be appropriate. This these comments, new category three has guiding principle in the Applicability
modification was in response to five been reorganized to limit the manner of section I of this document and is no
comments that raised questions about collection to noninvasive means. The longer simply specific to this category.
these issues. FDA and OPRR on their list of specific types of biological Category eight on the proposed list is
own initiative have added wording to specimens is now included as examples now category seven on the revised list.
set out in greater detail the conditions of the types of procedures that could fall This category was added to the 1981 list
that must be met in order for an IRB to within this category. with the proposal and concerns research
review research with a medical device Categories four and five on the on individual or group characteristics or
using expedited procedures. proposed list have been combined into behavior. At the time of the publication
Over 45 comments suggested certain one new category, category five, of the 1981 list, this category was not
changes to proposed category two, addressing research involving materials included in the FDA list because FDA
formerly category four in the 1981 list, collected or which will be collected routinely considered only the medical
addressing the collection of blood. The solely for nonresearch purposes. This risk to subjects in determining whether
suggested changes include addition of new category five was formed in a study imparted greater than minimal
many specific conditions, including response to comments that raised risk. Since that time, the scope of
limits on the amount withdrawn, questions about why the two categories research projects that are under FDA
collection procedures, and limits on the separated out existing and prospectively purview has expanded to include
physical condition of the subjects. In collected materials. The term activities that are listed in new category
response to these suggestions, the nonresearch purposes was seven. Therefore, studies related to
category has been reorganized to set maintained in new category five to FDA-regulated products might employ
general limits that the specific describe the origins of the research such methodology.
procedure must meet. The procedures materials. Over 30 comments requested this
for the collection of blood now include An explanatory note has been added category be simplified and rephrased so
finger stick, heel stick, ear stick, and to categories five and seven to clarify that researchers and IRBs could more
venipuncture. The four proposed that some research described in these readily determine whether their study is
subcategories were recombined as two categories may be exempt from the IRB eligible for expedited review. In
separate subcategories. The critical review under 45 CFR 46.101 of the HHS response, the following changes have
issues to be considered include weight, regulations for the protection of human been made. The condition that the
physical condition, and amount of subjects. Thus, the listing of those research does not involve stress has
blood to be collected. The first categories refers only to nonexempt been deleted; the subsections in the
subcategory (a) concerns healthy research. proposed list have been combined to
nonpregnant adults. The second Category six on the list proposed in eliminate the distinction between
subcategory (b) concerns all other adults November 1997 has become category research involving adults and research
and children. For this second four on the revised list and addresses involving children; research on oral
subcategory, the IRB will need to make the collection of data through history has been included in response to
certain judgments including: noninvasive procedures. In response to six comments; and specific research and
Consideration for the age, weight, and several comments that raised concerns research techniques have been noted.
health of the subjects in light of the about the use of anesthesia and sedation The category has been reorganized to
amount of blood to be collected, the with magnetic resonance imaging include research involving motivation,
frequency with which it will be procedures, expedited review will not identity, language, communication,
collected, and the collection procedure. be allowed for any procedure employing cultural beliefs or practices, and social
The final sentence of subcategory (b) anesthesia or sedation. In response to behavior as examples of research on
reads: For these subjects, the amount more than 24 comments, the general individual or group characteristics or
drawn may not exceed the lesser of 50 term noninvasive procedures now behavior. Methods of conducting such
mL or 3 mL per kg in an 8-week period applies to all procedures in this research are now separately listed and
and collection may not occur more than category. The specific procedures to have been expanded to include oral
2 times per week. While an expedited which expedited review was limited in history, program evaluation, human
review of research involving pregnant proposed category six, are included in factors evaluation, and quality
women is permissible under the revised new category four as examples of the assurance methodologies. As in new
section, this last sentence makes it clear types of procedures that could qualify category six, the qualification that
that the amount of blood that can be for expedited review. FDA and OPRR, requires consideration of certain kinds
drawn is subject to limitations greater on their own initiative, added wording of risks to subjects has been deleted
than those on healthy nonpregnant to clarify that studies intended to from this category, as it is now a general
adults. Also in response to public evaluate the safety and effectiveness of guiding principle, (C), which applies to
comment, the proposed phrase medical devices or using medical the entire list.
medically vulnerable adults has been devices that are not cleared or approved Category nine on the proposed list,
deleted. for marketing by FDA are generally not research previously approved by the
More than 24 comments were eligible for expedited review. convened IRB, received more than 50
received regarding category three, which Category seven on the proposed list is comments explicitly applauding this
was previously categories one and two now category six on the revised list and category. It has now been divided into
in the 1981 list, addressing the deals with the collection of data from new categories eight and nine. New Federal Register/Vol. 63, No. 216/Monday, November 9, 1998/Notices 60355
category eight identifies three situations (E) IRBs are reminded that the applying a dilute citric solution to the
in which research that is greater than standard requirements for informed tongue; (f) placenta removed at delivery;
minimal risk and has been initially consent (or its waiver, alteration, or (g) amniotic fluid obtained at the time
reviewed by the convened IRB, could exception) apply regardless of the type of rupture of the membrane prior to or
undergo subsequent continuing review of reviewexpedited or convened during labor; (h) supra- and subgingival
by the expedited review procedure. The utilized by the IRB. dental plaque and calculus, provided
new category nine concerns continuing (F) Categories one (1) through seven the collection procedure is not more
review of research that is not greater (7) pertain to both initial and continuing invasive than routine prophylatic
than minimal risk, but had to undergo IRB review. scaling of the teeth and the process is
initial review by a convened IRB accomplished in accordance with
Research Categories
because it did not meet the criteria of accepted prophylactic techniques; (i)
categories two through seven on this (1) Clinical studies of drugs and mucosal and skin cells collected by
list. medical devices only when condition buccal scraping or swab, skin swab, or
Certain other minimal changes have (a) or (b) is met. mouth washings; (j) sputum collected
been made for editorial purposes or to (a) Research on drugs for which an after saline mist nebulization.
clarify certain words that were used in investigational new drug application (21 (4) Collection of data through
the proposed list. Accordingly, the list CFR Part 312) is not required. noninvasive procedures (not involving
of categories of research which may be (Note: Research on marketed drugs that general anesthesia or sedation) routinely
reviewed by the IRB through an significantly increases the risks or decreases employed in clinical practice, excluding
expedited review procedure is amended the acceptability of the risks associated with procedures involving x-rays or
as set forth: the use of the product is not eligible for microwaves. Where medical devices are
expedited review.)
Categories of Research That May Be employed, they must be cleared/
(b) Research on medical devices for
Reviewed by the Institutional Review approved for marketing. (Studies
which (i) an investigational device
Board (IRB) Through an Expedited intended to evaluate the safety and
exemption application (21 CFR Part
Review Procedure1 effectiveness of the medical device are
812) is not required; or (ii) the medical
not generally eligible for expedited
Applicability device is cleared/approved for
review, including studies of cleared
marketing and the medical device is
(A) Research activites that (1) present medical devices for new indications.)
being used in accordance with its
no more than mimimal risk to human Examples: (a) physical sensors that
cleared/approved labeling.
subjects, and (2) involve only are applied either to the surface of the
(2) Collection of blood samples by
procedures listed in one or more of the body or at a distance and do not involve
finger stick, heel stick, ear stick, or
following categories, may be reviewed input of significant amounts of energy
venipuncture as follows:
by the IRB through the expedited review into the subject or an invasion of the
(a) From healthy, nonpregnant adults
procedure authorized by 45 CFR 46.110 subjects privacy; (b) weighing or testing
who weigh at least 110 pounds. For
and 21 CFR 56.110. The activities listed sensory acuity; (c) magnetic resonance
these subjects, the amounts drawn may
should not be deemed to be of minimal imaging; (d) electrocardiography,
not exceed 550 ml in an 8 week period
risk simply because they are included electroencephalography, thermography,
and collection may not occur more
on this list. Inclusion on this list merely detection of naturally occurring
frequently than 2 times per week; or
means that the activity is eligible for radioactivity, electroretinography,
(b) from other adults and children,2
review through the expedited review ultrasound, diagnostic infrared imaging,
considering the age, weight, and health
procedure when the specific doppler blood flow, and
of the subjects, the collection procedure,
circumstances of the proposed research echocardiography; (e) moderate
the amount of blood to be collected, the
involve no more than minimal risk to exercise, muscular strength testing,
frequency with which it will be
human subjects. body composition assessment, and
collected. For these subjects, the amount
(B) The categories in this list apply flexibility testing where appropriate
drawn may not exceed the lesser of 50
regardless of the age of subjects, except given the age, weight, and health of the
ml or 3 ml per kg in an 8 week period
as noted. individual.
(C) The expedited review procedure and collection may not occur more (5) Research involving materials (data,
may not be used where identification of frequently than 2 times per week.
documents, records, or specimens) that
the subjects and/or their responses (3) Prospective collection of biological
have been collected or will be collected
would reasonably place them at risk of specimens for research purposes by
solely for nonresearch purposes (such as
criminal or civil liability or be damaging noninvasive means.
medical treatment or diagnosis).
Examples: (a) hair and nail clippings
to the subjects financial standing,
employability, insurability, reputation, in a nondisfiguring manner; (b) (Note: Some research in this category may be
deciduous teeth at time of exfoliation or exempt from the HHS regulations for the
or be stigmatizing, unless reasonable
if routine patient care indicates a need protection of human subjects. 45 CFR
and appropriate protections will be
for extraction; (c) permanent teeth if 46.101(b)(4). This listing refers only to
implemented so that risks related to
research that is not exempt.)
invasion of privacy and breach of routine patient care indicates a need for
confidentiality are no greater than extraction; (d) excreta and external (6) Collection of data from voice,
minimal. secretions (including sweat); (e) video, digital, or image recordings made
(D) The expedited review procedure uncannulated saliva collected either in for research purposes.
may not be used for classified research an unstimulated fashion or stimulated (7) Research on individual or group
involving human subjects. by chewing gumbase or wax or by characteristics or behavior (including,
but not limited to, research on
1An expedited review procedure consists of a 2Children are defined in the HHS regulations as perception, cognition, motivation,
review of research involving human subjects by the persons who have not attained the legal age for identity, language, communication,
IRB chairperson or by one or more experienced consent to treatments or procedures involved in the cultural beliefs or practices, and social
reviewers designated by the chairperson from research, under the applicable law of the
behavior) or research employing survey,
among members of the IRB in accordance with the jurisdiction in which the research will be
requirements set forth in 45 CFR 46.110. conducted. 45 CFR 46.402(a). interview, oral history, focus group, 60356 Federal Register/Vol. 63, No. 216/Monday, November 9, 1998/Notices
program evaluation, human factors performance of the agencys functions; DEPARTMENT OF HEALTH AND
evaluation, or quality assurance (2) the accuracy of the estimated HUMAN SERVICES
methodologies. burden; (3) ways to enhance the quality,
(Note: Some research in this category may be utility, and clarity of the information to Health Care Financing Administration
exempt from the HHS regulations for the be collected; and (4) the use of [Document Identifier: HCFAR250]
protection of human subjects. 45 CFR automated collection techniques or
46.101(b)(2) and (b)(3). This listing refers other forms of information technology to Agency Information Collection
only to research that is not exempt.) minimize the information collection Activities: Proposed Collection;
(8) Continuing review of research burden. Comment Request
previously approved by the convened
Type of Information Collection AGENCY: Health Care Financing
IRB as follows:
Request: Extension of a currently Administration.
(a) Where (i) the research is
approved collection; Title of In compliance with the requirement
permanently closed to the enrollment of
Information Collection: Team of section 3506(c)(2)(A) of the
new subjects; (ii) all subjects have
Composition and Workload Report and Paperwork Reduction Act of 1995, the
completed all research-related
Supporting Regulations in 42 CFR Health Care Financing Administration
interventions; and (iii) the research
remains active only for long-term 493.1493.2001; Form No.: HCFA0670 (HCFA), Department of Health and
follow-up of subjects; or (OMB# 09380583); Use: This form Human Services, is publishing the
following summary of proposed
(b) Where no subjects have been requests resource utilization
collections for public comment.
enrolled and no additional risks have information on Medicare and Medicaid
Interested persons are invited to send
been identified; or providers, suppliers, and CLIA
comments regarding this burden
(c) Where the remaining research laboratories. The data is used to
estimate or any other aspect of this
activities are limited to data analysis. determine Federal reimbursement for all
collection of information, including any
(9) Continuing review of research, not participating health care facilities that
of the following subjects: (1) The
conducted under an investigational new accept Medicare and Medicaid
necessity and utility of the proposed
drug application or investigational beneficiaries.; Frequency: As needed;
information collection for the proper
device exemption where categories two Affected Public: State, Local, and Tribal
performance of the agencys functions;
(2) through eight (8) do not apply but Government, Business or other for-
(2) the accuracy of the estimated
the IRB has determined and
profit, and Not-for-profit institutions; burden; (3) ways to enhance the quality,
documented at a convened meeting that
Number of Respondents: 53; Total utility, and clarity of the information to
the research involves no greater than
Annual Responses: 449,252; Total be collected; and (4) the use of
minimal risk and no additional risks
Annual Hours: 71,667. automated collection techniques or
have been identified.
To obtain copies of the supporting other forms of information technology to
Dated: November 2, 1998. statement and any related forms for the minimize the information collection
William K. Hubbard, proposed paperwork collections burden.
Associate Commissioner for Policy Type of Information Collection
referenced above, access HCFAs Web
Coordination. Request: Extension of a currently
Site address at http://www.hcfa.gov/
[FR Doc. 9829748 Filed 11698; 8:45 am] approved collection.
regs/prdact95.htm, or E-mail your
BILLING CODE 416001M request, including your address, phone Title of Information Collection:
Skilled Nursing Facility (SNF) Resident
number, OMB number, and HCFA
Assessment MDS Data and Supporting
DEPARTMENT OF HEALTH AND document identifier, to Regulations in 42 CFR 413.343 and
HUMAN SERVICES Paperwork@hcfa.gov, or call the Reports 424.32.
Clearance Office on (410) 7861326. Form No.: HCFAR250 (OMB#
Health Care Financing Administration Written comments and 09380739).
[Document Identifier: HCFA0670] recommendations for the proposed Use: Skilled Nursing Facilities (SNFs)
information collections must be mailed are required to submit Resident
Agency Information Collection within 60 days of this notice directly to Assessment Data as described at 42 CFR,
Activities: Proposed Collection; the HCFA Paperwork Clearance Officer 483.20 in the manner necessary to
Comment Request designated at the following address: administer the payment rate
HCFA, Office of Information Services, methodology described in 42 CFR,
AGENCY: Health Care Financing
Security and Standards Group, Division 413.337. Pursuant to sections 4204(b)
Administration, HHS.
of HCFA Enterprise Standards, and 4214(d) of OBRA 1987, the current
In compliance with the requirement Attention: Louis Blank, Room N214 requirements related to the submission
of section 3506(c)(2)(A) of the 26, 7500 Security Boulevard, Baltimore, and retention of resident assessment
Paperwork Reduction Act of 1995, the Maryland 212441850. data for the 5th, 30th and 60th days
Health Care Financing Administration following admission, necessary to
(HCFA), Department of Health and Dated: November 2, 1998. administer the payment rate
Human Services, is publishing the John P. Burke III, methodology described in 413.337, is
following summary of proposed HCFA Reports Clearance Officer, HCFA Office subject to the Paperwork Reduction Act.
collections for public comment. of Information Services, Security and Frequency: Monthly.
Interested persons are invited to send Standards Group, Division of HCFA Affected Public: Business or other for-
comments regarding this burden Enterprise Standards. profit, and Not-for-profit.
estimate or any other aspect of this [FR Doc. 9829959 Filed 11698; 8:45 am] Number of Respondents: 17,000.
collection of information, including any Total Annual Responses: 204,000.
BILLING CODE 412003P
of the following subjects: (1) The Total Annual Hours: 3,865,885.
necessity and utility of the proposed To obtain copies of the supporting
information collection for the proper statement and any related forms for the