[Federal Register Volume 62, Number 217 (Monday, November 10, 1997)]
[Notices]
[Pages 60607-60611]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-29652]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Protection of Human Subjects: Suggested Revisions to the 
Institutional Review Board (IRB) Expedited Review List

AGENCY: Office for Protection from Research Risks, National Institutes 
of Health, HHS.

ACTION: Notice; request for comments.

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SUMMARY: The Office for Protection from Research Risks (OPRR), in 
consultation with the Food and Drug Administration (FDA), is requesting 
written comments relating to the proposed republication of the list 
that identifies certain research involving human subjects which may be 
reviewed by the Institutional Review Board (IRB) through the expedited 
review procedure authorized in Sec. 46.110 of 45 CFR Part 46. This list 
was originally published in 1981 and subsequently referenced in the 
Federal Policy (Common Rule) for the Protection of Human Subjects (56 
FR 28003). Pursuant to Sec. 46.110(a), the Secretary, HHS, has the 
authority to amend and republish the list. In the 16 years since the 
list was created, significant advances have been made in medicine and 
biological technology such that it is appropriate to consider revising 
this list

[[Page 60608]]

to include additional procedures or categories of research. OPRR seeks 
information and suggestions from the research community and public on 
possible revisions to the expedited review list.

DATES: Submit written comments on or before March 10, 1998.

ADDRESSES: Comments should be sent to Michele Russell-Einhorn, Director 
of Regulatory Affairs, Office for Protection from Research Risks, 
National Institutes of Health, 6100 Executive Blvd., Suite 3B01, 
Rockville, Md. 20892-7507. Since OPRR and FDA are simultaneously 
publishing identical lists, comments need not be sent to both agencies.

FOR FURTHER INFORMATION CONTACT: Michele Russell-Einhorn at the address 
above, or telephone (301) 435-5649 (not a toll-free number).

SUPPLEMENTARY INFORMATION: The Federal Policy (Common Rule) for the 
Protection of Human Subjects was published in the Federal Register on 
June 18, 1991 (56 FR 28003) and is employed by 17 Executive Branch 
agencies. This Federal Policy requires adherence to certain 
requirements by Federal agencies or institutions receiving Federal 
support for research activities involving human subjects. The Federal 
Policy has three cornerstones: review of any research involving human 
subjects by an Institutional Review Board (IRB); with limited 
exceptions, informed consent of all research subjects; and formal, 
written assurance of institutional compliance with the Policy. The 
Department of Health and Human Services' (HHS) codification of the 
Federal Policy can be found at 45 CFR Part 46.
    Section ____.110 of the Federal Policy provides for expedited 
review procedures for certain kinds of research involving no more than 
minimal risk, and for minor changes in approved research. This same 
section gives the Secretary, HHS, the authority to amend and republish 
the Expedited Review List as needed after consultation with the 
departments and agencies that are subject to the Federal Policy. The 
expedited review list that is referenced in the Federal Policy was 
originally published by the Secretary, HHS in 1981 as a Notice in the 
Federal Register of a list of categories of research that could be 
reviewed by the IRB through an expedited review procedure. The Food and 
Drug Administration (FDA) also references an expedited review list (21 
CFR Part 56) for matters under FDA's jurisdiction. The HHS and FDA 
lists differ slightly, in that item 9 on the 1981 HHS expedited review 
list regarding certain types of behavioral research is not included in 
the list referenced in 21 CFR Part 56.110.
    The current (1981) list allows an IRB to utilize the expedited 
review procedure for research activities involving no more than minimal 
risk and in which the only involvement of human subjects will be in one 
or more of the following categories (carried out through standard 
methods):
    (1) Collection of hair and nail clippings, in a nondisfiguring 
manner; deciduous teeth; and permanent teeth if patient care indicates 
a need for extraction. (2) Collection of excreta and external 
secretions including sweat, uncannulated saliva, placenta removed at 
delivery, and amniotic fluid at the time of rupture of the membrane 
prior to or during labor. (3) Recording of data from subjects 18 years 
of age or older using noninvasive procedures routinely employed in 
clinical practice. This includes the use of physical sensors that are 
applied either to the surface of the body or at a distance and do not 
involve input of matter or significant amounts of energy into the 
subject or an invasion of the subject's privacy. It also includes such 
procedures as weighing, testing sensory acuity, electrocardiography, 
electroencephalography, thermography, detection of naturally occurring 
radioactivity, diagnostic echography, and electroretinography. It does 
not include exposure to electromagnetic radiation outside the visible 
range (for example, x-rays, microwaves). (4) Collection of blood 
samples by venipuncture, in amounts not exceeding 450 milliliters in an 
eight-week period and no more often than two times per week, from 
subjects 18 years of age or older and who are in good health and not 
pregnant. (5) Collection of both supra-and subgingival dental plaque 
and calculus, provided the procedure is not more invasive than routine 
prophylactic scaling of the teeth and the process is accomplished in 
accordance with accepted prophylactic techniques. (6) Voice recordings 
made for research purposes such as investigations of speech defects. 
(7) Moderate exercise by healthy volunteers. (8) The study of existing 
data, documents, records, pathological specimens, or diagnostic 
specimens. (9) Research on individual or group behavior or 
characteristics of individuals, such as studies of perception, 
cognition, game theory, or test development, where the investigator 
does not manipulate subjects' behavior and the research will not 
involve stress to subjects. (10) Research on drugs or devices for which 
an investigational new drug exemption or an investigational device 
exemption is not required.
    OPRR, in consultation with FDA, is proposing to revise the 
expedited review list to include additional procedures or categories of 
research that may be reviewed under the expedited review procedure. 
Since 1981, OPRR has received some suggestions to this effect and has 
incorporated several into the proposed revision of the list that is 
published herein. OPRR seeks additional comments from the public on 
procedures or categories of research involving human subjects that may 
be amenable to review by the IRB chairperson or other designated IRB 
member instead of review by a convened meeting of the IRB.
    The following is a proposed revision of the current expedited 
review list found at 46 FR 8392 (Jan. 26, 1981) and 46 FR 8980 (Jan. 
27, 1981). FDA is simultaneously publishing an identical list. Judgment 
is reserved on whether OPRR and FDA will publish identical lists after 
comments are received and reviewed. OPRR welcomes and encourages 
comments from the research community and public.

Research Activities Which May Be Reviewed Through Expedited Review 
Procedures <SUP>1</SUP>
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    \1\ The expedited review procedure consists of a review of 
research involving human subjects by the IRB chairperson or by one 
or more experienced reviewers designated by the chairperson from 
among members of the IRB in accordance with the requirements set 
forth in Section ____.110.
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    Research activities (carried out through standard methods) which 
involve (1) no more than minimal risk, and (2) appear in one or more of 
the following categories may be reviewed by the Institutional Review 
Board through the expedited review procedure authorized in 45 CFR 
46.110 and 21 CFR 56.110. The activities that appear on this list 
should not be deemed to be of minimal risk simply because they are 
included on this list. Appearance on this list merely means that the 
activity is eligible for review through the expedited process when the 
specific circumstances of the proposed research involve no more than 
minimal risk to the human subjects. The categories in this list apply 
regardless of the age of subjects, except as noted.
    (1) Research on drugs or devices for which an investigational new 
drug exemption or an investigational device exemption is not required.
    (2) Collection of blood samples by finger stick or venipuncture as 
follows:
    (a) From healthy, nonpregnant adults <SUP>2</SUP> who weigh at 
least 110 pounds, in

[[Page 60609]]

amounts not exceeding 550 ml in an 8 week period and no more than 2 
times per week.
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    \2\ Throughout this document, when OPRR refers to ``adult,'' 
OPRR defers to state law for determining the age of majority.
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    (b) From healthy, pregnant adults who weigh at least 110 pounds, in 
amounts not exceeding 100 ml in an 8 week period and no more than 2 
times per week.
    (c) From healthy children, in amounts not exceeding 3 ml/kg in an 8 
week period and no more than 2 times per week.
    (d) From medically vulnerable adults who weigh at least 110 pounds, 
in amounts not exceeding 50 ml in an 8 week period and no more than 2 
times per week.
    (3) Prospective collection for research purposes of the following 
biological specimens:
    (a) Hair and nail clippings in a nondisfiguring manner.
    (b) Deciduous teeth at time of exfoliation, or if routine patient 
care indicates a need for extraction.
    (c) Permanent teeth if routine patient care indicates a need for 
extraction.
    (d) Excreta and external secretions (including sweat).
    (e) Uncannulated saliva collected either in an unstimulated fashion 
or stimulated by chewing gumbase or wax or by applying a dilute citric 
solution to the tongue.
    (f) Placenta removed at delivery.
    (g) Amniotic fluid obtained at the time of rupture of the membrane 
prior to or during labor.
    (h) Supra- and subgingival dental plaque and calculus, provided the 
collection procedure is not more invasive than routine prophylactic 
scaling of the teeth and the process is accomplished in accordance with 
accepted prophylactic techniques.
    (i) Stool cultures obtained by rectal swab.
    (j) Mucosal and skin cells collected by buccal scraping or swab, 
skin swab, or mouth washings.
    (k) Sputum collected after saline mist nebulization.
    (4) Research involving existing identifiable data, documents, 
records, or biological specimens (including pathological or diagnostic 
specimens) where these materials, in their entirety, have been 
collected prior to the research, for a purpose other than the proposed 
research.
    (5) Research involving solely (a) prospectively collected 
identifiable residual or discarded specimens, or (b) prospectively 
collected identifiable data, documents, or records, where (a) or (b) 
has been generated for nonresearch purposes.
    (6) Collection of data through use of the following procedures:
    (a) Noninvasive procedures routinely employed in clinical practice 
and not involving exposure to electromagnetic radiation outside the 
visible range (i.e., not involving x-rays, microwaves, etc.).
    (b) Physical sensors that are applied either to the surface of the 
body or at a distance and do not involve input of significant amounts 
of energy into the subject or an invasion of the subject's privacy.
    (c) Weighing, testing sensory acuity, electrocardiography, 
electroencephalography, thermography, detection of naturally occurring 
radioactivity, electroretinography, echography, sonography, ultrasound, 
magnetic resonance imaging (MRI), diagnostic infrared imaging, doppler 
blood flow, and echocardiography.
    (d) Moderate exercise, muscular strength testing, body composition 
assessment, and flexibility testing involving healthy subjects.
    (7) Collection of data from voice, video, or image recordings made 
for research purposes where identification of the subjects and/or their 
responses would not reasonably place them at risk of criminal or civil 
liability or be damaging to the subjects' financial standing, 
employability, or reputation.
    (8) Research on individual or group characteristics or behavior 
(including but not limited to research involving perception, cognition, 
surveys, interviews, and focus groups) as follows:
    (a) Involving adults, where (i) the research does not involve 
stress to subjects, and (ii) identification of the subjects and/or 
their responses would not reasonably place them at risk of criminal or 
civil liability or be damaging to the subjects' financial standing, 
employability, or reputation.
    (b) Involving children, where (i) the research involves neither 
stress to subjects nor sensitive information about themselves, or their 
family; (ii) no alteration or waiver of regulatory requirements for 
parental permission has been proposed; and (iii) identification of the 
subjects and/or their responses would not reasonably place them or 
their family members at risk of criminal or civil liability or be 
damaging to the financial standing, employability, or reputation of 
themselves or their family members.
    (9) Research previously approved by the convened IRB as follows:
    (a) Where (i) the research is permanently closed to the enrollment 
of new subjects; (ii) all subjects have completed all research-related 
interventions; and (iii) the research remains active only for long-term 
follow-up of subjects; or
    (b) Where the research remains active only for the purposes of data 
analysis; or
    (c) Where the IRB has determined that the research involves no 
greater than minimal risk and no additional risks have been identified; 
or
    (d) Where no subjects have been enrolled and no additional risks 
have been identified.
    The following tabulation of changes is included to enable readers 
to more easily compare the categories of research included in both 
lists.

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                                         1981 (Current) expedited review
     Proposed expedited review list                    list             
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1. Research on drugs or devices for      Unchanged; currently number 9. 
 which an investigational new drug                                      
 exemption or an investigational device                                 
 exemption is not required.                                             
2. Collection of blood samples by        Currently number 4, limited to 
 finger stick or venipuncture as          venipuncture; ``finger stick''
 follows:                                 not included                  
    (a) From healthy, nonpregnant        Amounts currently limited to   
     adults, in amounts not exceeding     450 ml                        
     550 ml in an 8 week period and no                                  
     more than 2 times per week.                                        
    (b) From healthy, pregnant adults,   Not included.                  
     in amounts not exceeding 100 ml in                                 
     an 8 week period and no more than                                  
     2 times per week.                                                  
    (c) From healthy children, in        Not included.                  
     amounts not exceeding 3 ml/kg in                                   
     an 8 week period and no more than                                  
     2 times per week.                                                  
    (d) From medically vulnerable        Not included.                  
     adults, in amounts not exceeding                                   
     50 ml in an 8 week period and no                                   
     more than 2 times per week.                                        
3. Prospective collection for research   ``Prospective'' and ``for      
 purposes of the following biological     research purposes'' currently 
 specimens:                               not included.                 
    (a) Hair and nail clippings in a     Currently part of number 1;    
     nondisfiguring manner.               unchanged.                    

[[Page 60610]]

                                                                        
    (b) Deciduous teeth at time of       Currently part of number 1;    
     exfoliation, or if routine patient   ``deciduous teeth'' included  
     care indicates a need for            without qualifiers.           
     extraction.                                                        
    (c) Permanent teeth if routine       Currently part of number 1;    
     patient care indicates a need for    ``routine'' not included.     
     extraction.                                                        
    (d) Excreta and external secretions  Currently part of number 2;    
     (including sweat).                   unchanged.                    
    (e) Uncannulated saliva collected    Currently part of number 2;    
     either in an unstimulated fashion    ``uncannulated saliva''       
     or stimulated by chewing gumbase     included without qualifiers.  
     or wax or by applying a dilute                                     
     citric solution to the tongue.                                     
    (f) Placenta removed at delivery...  Currently part of number 2;    
                                          unchanged.                    
    (g) Amniotic fluid obtained at the   Currently part of number 2;    
     time of rupture of the membrane      unchanged.                    
     prior to or during labor.                                          
    (h) Supra- and subgingival dental    Currently number 5;            
     plaque and calculus, provided the    ``procedure'' was not         
     collection procedure is not more     qualified with the word       
     invasive than routine prophylactic   ``collection.''               
     scaling of the teeth and the                                       
     process is accomplished in                                         
     accordance with accepted                                           
     prophylactic techniques.                                           
    (i) Stool cultures obtained by       Not included.                  
     rectal swab.                                                       
    (j) Mucosal and skin cells           Not included.                  
     collected by buccal scraping or                                    
     swab, skin swab, or mouth washings.                                
    (k) Sputum collected after saline    Not included.                  
     mist nebulization.                                                 
4. Research involving existing           Currently number 8; stated as: 
 identifiable data, documents, records,   ``The study of existing data, 
 or biological specimens (including       documents, records,           
 pathological or diagnostic specimens)    pathological specimens, or    
 where these materials, in their          diagnostic specimens.''       
 entirety, have been collected prior to                                 
 the research, for a purpose other than                                 
 the proposed research.                                                 
5. Research involving solely (a)         Not included.                  
 prospectively collected identifiable                                   
 residual or discarded specimens, or                                    
 (b) prospectively collected                                            
 identifiable data, documents, or                                       
 records, where (a) or (b) has been                                     
 generated for nonresearch purposes.                                    
6. Collection of data through use of     Currently number 3;            
 the following procedures:                ``recording'' instead of      
                                          ``collection.''               
    (a) Noninvasive procedures           Currently number 3; limited to 
     routinely employed in clinical       subjects 18 years of age or   
     practice and not involving           older.                        
     exposure to electromagnetic                                        
     radiation outside the visible                                      
     range (i.e., not involving x-rays,                                 
     microwaves, etc.).                                                 
    (b) Physical sensors that are        Currently number 3; limited to 
     applied either to the surface of     subjects 18 years of age or   
     the body or at a distance and do     older.                        
     not involve input of significant                                   
     amounts of energy into the subject                                 
     or an invasion of the subject's                                    
     privacy.                                                           
    (c) Weighing, testing sensory        Currently number 3; limited to 
     acuity, electrocardiography,         subjects 18 years of age or   
     electroencephalography,              older; limited echography to  
     thermography, detection of           ``diagnostic echography'';    
     naturally occurring radioactivity,   does not include ``sonography,
     electroretinography, echography,     ultrasound, magnetic resonance
     sonography, ultrasound, magnetic     imaging (MRI), diagnostic     
     resonance imaging (MRI),             infrared imaging, doppler     
     diagnostic infrared imaging,         blood flow, and               
     doppler blood flow, and              echocardiography.''           
     echocardiography.                                                  
    (d) Moderate exercise, muscular      Currently number 7; limited to 
     strength testing, body composition   ``Moderate exercise by healthy
     assessment, and flexibility          volunteers.''                 
     testing involving healthy subjects.                                
7. Collection of data from voice,        Currently number 6; stated as: 
 video, or image recordings made for      ``Voice recordings made for   
 research purposes where identification   research purposes such as     
 of the subjects and/or their responses   investigations of speech      
 would not reasonably place them at       defects.''                    
 risk of criminal or civil liability or                                 
 be damaging to the subjects' financial                                 
 standing, employability, or reputation.                                
8. Research on individual or group       Currently number 9, stated as  
 characteristics or behavior (including   follows: Research on          
 but not limited to research involving    individual or group behavior  
 perception, cognition, surveys,          or characteristics of         
 interviews, and focus groups) as         individuals, such as studies  
 follows:                                 of perception, cognition, game
                                          theory, or test development,  
                                          where the investigator does   
                                          not manipulate subjects'      
                                          behavior and the research will
                                          not involve stress to         
                                          subjects.''                   
    (a) Involving adults, where (i) the                                 
     research does not involve stress                                   
     to subjects, and (ii)                                              
     identification of the subjects and/                                
     or their responses would not                                       
     reasonably place them at risk of                                   
     criminal or civil liability or be                                  
     damaging to the subjects'                                          
     financial standing, employability,                                 
     or reputation.                                                     
    (b) Involving children, where (i)                                   
     the research involves neither                                      
     stress to subjects nor sensitive                                   
     information about themselves, or                                   
     their family; (ii) no alteration                                   
     or waiver of regulatory                                            
     requirements for parental                                          
     permission has been proposed; and                                  
     (iii) identification of the                                        
     subjects and/or their responses                                    
     would not reasonably place them or                                 
     their family members at risk of                                    
     criminal or civil liability or be                                  
     damaging to the financial                                          
     standing, employability, or                                        
     reputation of themselves or their                                  
     family members.                                                    
9. Research previously approved by the   Not Included.                  
 convened IRB as follows:                                               
    (a) Where (i) the research is                                       
     permanently closed to the                                          
     enrollment of new subjects; (ii)                                   
     all subjects have completed all                                    
     research-related interventions;                                    
     and (iii) the research remains                                     
     active only for long-term follow-                                  
     up of subjects; or                                                 
    (b) Where the research remains                                      
     active only for the purposes of                                    
     data analysis; or                                                  

[[Page 60611]]

                                                                        
    (c) Where the IRB has determined                                    
     that the research involves no                                      
     greater than minimal risk and no                                   
     additional risks have been                                         
     identified; or                                                     
    (d) Where no subjects have been                                     
     enrolled and no additional risks                                   
     have been identified                                               
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    Dated: October 31, 1997.
Gary B. Ellis,
Director, Office for Protection from Research Risks.
[FR Doc. 97-29652 Filed 11-5-97; 3:51 pm]
BILLING CODE 4140-01-P