Subpart D Review of Pending NHLBI Grant Entitled "Characterization of Mucus and Mucins in Bronchoalveolar Lavage Fluids from Infants with Cystic Fibrosis"

The Office for Human Research Protections (OHRP) is soliciting public review and comment pursuant to Department of Health and Human Services (HHS) regulations at 45 CFR 46.407 on the above-referenced research protocol.

HHS regulations at 45 CFR part 46, subpart D, provide additional protections to children involved in research.  Under the requirements of subpart D, if an institutional review board (IRB) reviewing a protocol to be conducted or supported by HHS does not believe that the proposed research involving children meets requirements for approval under 45 CFR 46.404 (research not involving greater than minimal risk), 46.405 (research involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects), or 46.406 (research involving greater than minimal risk and no prospect of direct benefit to the individual subjects but likely to yield generalizable knowledge about the subject's disorder or condition), but that the research presents a reasonable opportunity to further the understanding, prevention or alleviation of a serious problem affecting the health or welfare of children, the IRB may refer the proposed research to the Secretary of HHS for a determination regarding whether the research is otherwise approvable under subpart D.  Under the process outlined in 45 CFR 46.407, the Secretary must consult with experts in relevant disciplines, and provide the opportunity for public review and comment, before determining whether the proposed research may be conducted or supported by HHS.

The above-referenced research protocol proposes to study the changes in bronchoalveolar lavage fluid (BALF) of infants diagnosed with cystic fibrosis in the neonatal period.  The proposed study would enroll infants with a clinical diagnosis of cystic fibrosis in the neonatal period and would obtain BALF from these infants via flexible fiberoptic bronchoscopy at three time points: (1) after diagnosis, within the first 6 weeks after birth; (2) at 6 months of age; and (3) at 12 months of age.  The goals of the proposed study are to: (a) quantify mucin in BALF and compare quantities before infection vs. after infection onset in cystic fibrosis; (b) correlate mucin quantity with measures of infection (quantitative bacteriology) and inflammation (cell numbers, neutrophil products, and inflammatory cytokines); and (c) isolate mucus plugs and characterize their histology before and after infection, in order to more accurately describe early relationships among mucus obstruction, infection and inflammation.

OHRP is requesting comments on the following questions related to the study:

1.  What are the types and degrees of risk that this research presents to the subjects?

2.  What are the potential benefits, if any, to the subjects and to children in general?

3.  Does the research present a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children?

4.  If conducted as proposed in the above-cited protocol, would the research be conducted in accordance with sound ethical principles?  In formulating a response, commenters may wish to consider whether the proposed protocol satisfies all the requirements under HHS regulations at 45 CFR 46.111 (criteria for IRB approval of research).

5.  Have adequate provisions been made for soliciting the assent of children and the permission of their parents or guardians?

To be considered, comments on this proposed research protocol must be submitted on or before 4:30 PM EST, July 28, 2003.  Written comments should be submitted to Ms. Kelley Booher, Division of Policy, Planning, and Special Projects, OHRP, 1101 Wootton Parkway, Suite 200, The Tower Building, Rockville, MD 20852.  Comments may also be submitted via facsimile at 301-402-2071 or by email to: 407panel02@osophs.dhhs.gov .  Following public review and comment, the Secretary of HHS will make a final determination on whether HHS may support this research protocol.  If approved, this research would be supported by a grant awarded by the National Heart, Lung, and Blood Institute, National Institutes of Health.

Please note that some of the information in the following documents is exempt from disclosure under existing Federal statutes and has been redacted.
  1. Federal Register Notice Vol. 68, No. 114, pages 35414-5, dated June 13, 2003: Solicitation of Public Review and Comment, available at  http://ohrp.osophs.dhhs.gov/references/fr06-13n.pdf  [PDF document].
  2. Correspondence from the principal investigator and the research institution referring the proposed research protocol to the Secretary of HHS for consideration under 45 CFR Part 46.407   [PDF Format  PDF document, see bottom of page to obtain free reader] 
  3. Original IRB protocol application   [PDF Format  PDF document, see bottom of page to obtain free reader] 
  4. Correspondence between the IRB and the principal investigator;
  5. IRB deliberations on the proposed research;
  6. Subsequent correspondence between OHRP and the research institution;
  7. Relevant excerpts of the NIH grant application  [PDF Format PDF document, see bottom of page to obtain free reader]
  8. Latest version of parental permission document  [PDF Format PDF document, see bottom of page to obtain free reader]   [HTML Format]
  9. Review of proposed research by the Cystic Fibrosis Foundation's Data and Safety Monitoring board  [PDF Format PDF document, see bottom of page to obtain free reader]   [HTML Format]
  10. UNC bronchoscopy complication data  [PDF Format PDF document, see bottom of page to obtain free reader]   [HTML Format]
  11. Individual expert reports solicited pursuant to HHS Regulations at 45 CFR 46.407;

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Updated June 13, 2003