GAB Decision 340
August 30, 1982 UCLA School of Medicine; Docket No. 82-16 Ford,
Cecilia; Teitz, Alexander Settle, Norval
The principal investigator (appellant) of a research grant awarded to
the University of California, Los Angeles, appealed a decision by the
National Heart, Lung, and Blood Institute /1/ to withhold noncompeting
continuation awards after the first year of support (April 1, 1981 -
March 31, 1982). /2/ The amount of funding withheld was $162,283.
The respondent based its decision on its finding that the principal
investigator had violated regulations at 45 CFR Part 46 (1979) regarding
protection of human subjects in research, and NIH Guidelines for
Research Involving Recombinant DNA Molecules (NIH Guidelines). /3/
(2) Specifically, the appellant performed experiments on human subjects
in Israel and Italy during the summer of 1980, in which he used
recombinant DNA genes. He did not receive permission from either UCLA
or NIH prior to performing these experiments, in violation of 45 CFR
46.102 and 46.116, the UCLA General Assurance filed with NIH pursuant to
section 46.105, and the NIH Guidelines. Furthermore, in Israel he used
recombinant DNA genes without informing the appropriate Israeli
authorities prior to using the genes.
The appellant admitted his actions and did not contradict the
respondent's conclusion that the regulations and guidelines, which
placed restrictions on performing experiments on humans and using
recombinant DNA genes in the experiments, applied to his actions. /4/
Although the appellant argued that he was unaware of some of the
requirements in UCLA's General Assurance, there is little doubt that he
knew he must inform appropriate institutional committees at UCLA prior
to performing such research. /5/ The appellant, however, did request
further review of the decision to deny the continuation awards, because
he believed that the members of the National Heart, Lung, and Blood
Institute Advisory Council had not considered a letter he wrote in which
he explained the basis for his actions. The respondent interpreted this
to mean that the issue before the Board was whether the respondent acted
upon inadequate information. We believe that the appellant's request
also involved a question of whether the sanction imposed was appropriate
given the appellant's explanation of his actions. Thus, we considered
that the appellant raised two issues: whether the respondent based its
decision upon adequate information after a fair process, and whether the
sanctions imposed, particularly the decision to deny the continuation
awards, were reasonable.
Applicable Regulations and Guidelines
Human subject experimentation supported by DHHS grants is regulated
by 45 CFR Part 46.The guiding policy is that protecting the rights and
welfare of subjects is primarily the responsibility of the institution
which receives or is accountable for DHHS funds supporting (3) the
activity. Thus, an Institutional Review Board must review and approve
activity involving human subjects that is supported by DHHS grants or
contracts. Section 46.102(a). Assurance must be provided to DHHS that
the institution and its personnel will adhere to the policy and
standards.Sections 46.104 and 46.105. Any human experiments conducted
at cooperating institutions must also be approved by the Institutional
Review Board. Section 46.116.
The UCLA General Assurance, approved by DHHS on December 2, 1977, and
UCLA instructions on application for human subject review require that
University personnel performing investigations placing humans at risk
must seek review and approval by the Institutional Review Committee.
Furthermore, an investigator must obtain approval from any collaborating
institution's reviewing entity and must submit that approval to UCLA.
The NIH Guidelines are applicable to all recombinant DNA research
supported by NIH funds, or sponsored by an institution that receives
support from NIH. Section IV-B. The Guidelines require that all
proposed recombinant DNA experiments, except those described in Sections
I-E and III-O, are to be reviewed for compliance with the Guidelines,
and prior approval must be obtained from an Institutional Biosafety
Committee. Section IV-D-3-a.
General Information
The appellant is a professor at the UCLA School of Medicine, and was,
at the time of his actions, also chief of a division in the School of
Medicine. He was the principal investigator for research grant awards
from three components of the National Institutes of Health -- the
National Heart, Lung, and Blood Institute; the National Arthritis,
Diabetes, and Digestive and Kidney Diseases Institute; and the National
Cancer Institute. The grant at issue here is one which involves
evaluation of the effectiveness of gene transfer techniques for
inserting new genetic information into mouse hematopoietic cells. /6/
The appellant's experiments led him to believe that inserting new
genetic information, using the gene transfer techniques he had
developed, into a human affilicted with one of certain severe,
life-threatening diseases caused by genetic abnormalities affecting
blood cells, would create enough normal cells to ameliorate the disease.
(4) In May 1979 the appellant had requested review by the UCLA Human
Subject Protection Committee of an experimental plan relating to
patients with sickle cell disease. The Committee had not reached a
decision about the experiments, even though the proposal had been before
it for one year, at the time the appellant performed his experiments in
Israel and Italy (July 1980). After his return from abroad, the
appellant learned that the UCLA Human Subject Protection Committee had
denied approval of his proposal because it believed that further
experiments in mice should be performed before any experiments were
performed on humans. /7/
The appellant submitted a research proposal, similar to the one
submitted to UCLA, to the appropriate human subject protection committee
in Israel, and received approval to conduct the experiment. In Italy,
approval is obtained through the heads of major clinical divisions; the
appellant presented his research plan orally and received oral approval
from the head of one division. He also obtained written consent from
the patients in both countries.
None of the proposals the appellant submitted involved the use of
recombinant genes regulated by federal guidelines. Despite that fact,
the appellant used recombinant DNA genes when he performed the
experiments in Israel and Italy. He later stated that he made the
decision to use recombinant genes because their use would increase the
possibility that the experiments would work, and because there was no
additional risk to the patient. Respondent's submission, p. 14, Letter
from appellant, p. 5, contained in UCLA Report (see below). Upon
returning to the United States, the appellant informed the Israeli
doctors by telephone that he had used recombinant genes for the
transfer. The record shows that the review committee in Israel had
specifically inquired of both UCLA and NIH whether the research proposed
by the appellant came within the NIH Guidelines, and that when the
Israelis learned that recombinant DNA had been used, they were concerned
about why they were not told in advance. Respondent's submission, p.
510, Letter from head of Israel's authorizing committee; Appellanths
submission, Memorandum from Chairman, NIH Ad Hoc Committee on UCLA
Report, pp. 14-16. (5) The Process Used by NIH to Reach a Decision
Upon learning that the appellant had performed experiments in Israel
and Italy during the summer of 1980 which may have violated federal
regulations and NIH guidelines, NIH requested further information from
UCLA.In October 1980, UCLA submitted a report to NIH (UCLA Report),
which consisted of a letter from the apellant describing his activities
in Israel and Italy, some additional information contained in a
confidential memorandum from a UCLA Vice-Chancellor, a copy of research
protocol submitted by the appellant to the UCLA institutional committee
responsible for reviewing proposals involving human subjects, and other
information relating to the work performed in Israel and Italy.
The Director of NIH established an Ad Hoc Committee on the UCLA
Report, charging the Committee to advise him whether the appellant's
actions violated the human subject protection regulations and the NIH
Guidelines, and, if so, what action NIH should take. Furthermore, the
Director asked the Committee to consider and advise him whether there
was a clear transgression of the spirit of the Guidelines or
regulations, and whether NIH should take steps to safeguard the intent
of the rules.
The Ad Hoc Committee requested further informaton from UCLA and the
appellant three times during the course of its deliberations. It sent a
copy of its draft report to UCLA and to the appellant, inviting their
comments. The appellant declined to comment at that time, and the
report was made final on May 18, 1981.
The Report discussed the scope of the review, the process used for
the review, the facts described in the UCLA Report and responses to the
Committee's inquiries, the relationship of the appellant's actions to
the rules, and the sanctions applied to the appellant by UCLA after the
institution's review of his actions.
The Ad Hoc Committee concluded that the federal regulations and NIH
Guidelines applied to the appellant's use of recombinant DNA genes in
human experiments in Israel and Italy, and that the appellant violated
the regulations and Guidelines by failing to obtain prior aproval by the
UCLA Institutional Review Board or by the Institutional Biosafety
Committee, and failing to obtain approval in Italy by any human subjects
review committee. The Ad Hoc Committee also concluded that the
appellant changed the protocol from that approved by the review
committee in Israel to a procedure not approved. The Ad Hoc Committee
(6) stated that since it found specific violations of the rules, it did
not consider the alternative charge concerning violations of the spirit
of the rules. The Ad Hoc Committee also recommended certain sanctions,
which will be discussed later.
Pursuant to the request of the Director of NIH, the Advisory Council
for the National Heart, Lung, and Blood Institute considered the Ad Hoc
Committee's report on September 25, 1981, and voted, with one dissenting
vote, to support the actions taken by NIH, and to add two additional
sanctions.
The appellant wrote a letter, in which he explained the motivation
for his actions, and sent it to NIH. The letter was dated September 17,
1981, and, although it was received after the Institute's Advisory
Council meeting, it was forwarded to the Council members. None of the
members requested reconsideration of the question at the next meeting,
although the member who voted against the motion to terminate the
research grant wrote a letter explaining his view. That letter was also
forwarded to the Acting Director of the Institute.
Sanctions Applied to the Appellant by NIH
The Ad Hoc Committee recommended the following sanctions:
1) For each new research protocol by the appellant, involving human
subjects, NIH must approve, before the appellant can proceed with the
research, a written assurance of compliance, including certification
that the Institutional Review Board has reviewed and approved the
protocol.
2) Any of the appellant's projects involving recombinant DNA which
are covered by the NIH Guidelines must be approved in advance by the
Institutional Biosafety Committee and the NIH.
3) A copy of the Report should be sent to the Director of any NIH
Bureau, Institute, or Division currently providing support for the
appellant, so that the Director may consider whether the grants should
be continued, and what conditions should be placed on them.
4) A copy of the Report should be supplied to the Initial Review
Groups to which any future competing application for support are
assigned, and to the Director of that Institute, in order for the Report
to be considered in determining whether to award the grant, and under
what conditions.
(7) The Acting Directors of the National Heart, Lung and Blood
Institute and of NIH then decided to adopt these recommendations, and to
adopt the recommendation of the Institute's Advisory Council to withhold
the continuation awards for the grant for which the appellant was
principal investigator. /8/ NIH notified UCLA of the decision to
discontinue funding in a letter dated January 19, 1982.
Discussion
A. The NIH Decision Process
NIH does not have a particular process by which violations of the
applicable federal regulations and guidelines may be considered in
deciding whether to make a noncompeting continuation award.
Furthermore, decisions concerning noncompeting continuation awards are
discretionary.
The process used by NIH to review the case and obtain recommendations
about the existence of violations and their consequences was quite
thorough. UCLA investigated and prepared a report, which included a
complete statement by the appellant. The Ad Hoc Committee asked further
questions and obtained answers from UCLA, and the appellant participated
in the preparation of those responses. The Ad Hoc Committee offered the
appellant an opportunity for comment on its draft report before sending
it to the Director. The Director did not make a decision until after
the National Advisory Councils had thoroughly discussed the Report, and
made recommendations. The National Heart, Lung, and Blood Institute's
Advisory Council members received the appellant's letter, submitted four
months after his comments were requested, and were told that they could
reconsider their recommendations. The Director, then, was presented not
only with a complete report, but with varying recommendations from three
Advisory Councils, and a letter from one member of the National Heart,
Lung, and Blood Institute's Advisory Council who held a minority view.
The appellant had sufficient opportunity to present his case. The
appellant has not presented any evidence to this Board that the process
was unfair in any other way.
We conclude on the basis of the evidence presented that the process
was thorough, objective, and fair. We also conclude that the decision
by the NIH Acting Director was made on the basis of adequate
information.
(8) B. Review of the Sanctions Applied
We find (and it is not substantially disputed by appellant) that the
appellant acted in a manner contrary to the federal regulations and
guidelines, and that those rules applied to his actions. The
appellant's position primarily is that he has been dealt with too
harshly under the circumstances. The usual standard for review of an
agency's choice of sanction is for abuse of discretion. The
relationship of a sanction to policy is a matter for agency competence,
not to be overturned unless unwarranted in law or without justification
in fact. Butz v. Glover Livestock Co., 411 U.S. 182 (1973); Cross v.
U.S., 512 F.2d 1212, 1218 (4th Cir. 1975). /9/
Federal regulations and guidelines provide authority to withhold
continuation awards, and terminate, suspend, or impose conditions upon
grants. 42 CFR 52.6; 45 CFR Part 74, Subpart M; 45 CFR 74.7, 46.121
and .122; NIH Guidelines, Sections IV-G-1 and -2. NIH chose to
withhold the continuation funding of one grant and place conditions on
all others. These sancations are authorized by the regulations and
guidelines, and are thus warranted in law. /10/
(9) The appellant, in his letter of September 17, 1981, complained
about the unsatisfactory nature of the human subject protection review
mechanism at the institutional level, citing such questionable practices
as delay by the committee in deciding it needed external expertise, and
in reaching a decision; lack of feedback to the investigator concerning
progress of the review; lack of confidentiality relating to the
protocol submitted for review; and lack of expertise by the members of
the committee in areas crucial to the subject matter of the protocol.
The inadequacy of the process with regard to the protocol submitted by
the appellant to UCLA may be one reason he elected to proceed with the
use of recombinant DNA genes without waiting for approval; however,
this Board cannot ignore his violation of the applicable regulations and
Guidelines by accepting the existence of an allegedly faulty process at
UCLA as justification for his actions.
The appellant also pointed out the existence of legitimate concerns
about the restrictive nature of the NIH Guidelines, leading to
scientifically less satisfactory experimental designs. He also pointed
out that, in his experiments, the use of nonrecombinant molecules, for
which there are no guidelines, would not differ significantly in
biological consequences from the use of recombinant DNA.
The concerns which led to the development of the Guidelines are
serious and legitimate. Their objective is to ensure that experimental
DNA recombination will have no ill effects on those engaged in the work,
the general public, or the environment. 41 Fed. Reg. 27904. The
Guidelines were developed by scientists with the aid of consultants on
law, ethics, consumer affairs, and the environment, and the Guidelines'
were adopted only after considerable public input and debate by the
Advisory Committee. A primary issue was how to balance concerns for
public safety with legitimate scientific research goals. There was
apparently disagreement among the scientific community, including those
comprising the Advisory Committee, about the nature and level of
possible hazards resulting from recombinant DNA research. 41 Fed. Reg.
27904. The Guidelines have been revised several times since (10) their
original publication (see n. 3), and they include procedures for their
future revision. All amendments were adopted only after publication for
comment and a public meeting of the Advisory Committee. Thus, revision
of the Guidelines may be accomplished whenever a general perception on
the part of the scientific community exists that alteration is
necessary.
The Ad Hoc Committee and the National Advisory Councils which
considered the appellant's actions were composed of scientists to whom
the facts and scientific data were known. They concluded, among other
things, that the available experimental data was insufficient to warrant
experimentation in humans at that time. No evidence has been presented
to the Board that the decisionmakers based their decision on invalid or
illegitimate reasons.
One member of the National Heart, Lung, and Blood Institute indicated
that he believed the sanction withholding the award was too harsh.
Although one court has reversed a sanction for its severity, Arthur
Lipper Corp. v. SEC, 547 F.2d 171, 183 (2d Cir. 1976), reh. denied, 551
F.2d 915 (1977), cert. denied, 434 U.S. 1009, 98 S.Ct. 719 (1978), the
scope of review set forth in the majority of the cases does not provide
for overturning a sanction for harshness alone. We do not believe that
the severity of the sanction in this instance was so great compared to
the actions of the appellant that it might be deemed arbitrary. The
purposes of the regulations and Guidelines are not to be taken lightly,
and it appears that the Ad Hoc Committee and the Advisory Council
members wished to stress the spirit and intent of the rules. An
after-the-fact assertion that the appellant's actions did not result in
any danger to the patients or others does not overcome the concerns of
the scientific community that someone's unreviewed actions might pose
such a threat.
Based on the foregoing, we conclude that the sanctions applied were
clearly reasonable in relation to the appropriate institutional concern
about activities in an awesome and potentially dangerous area of
science.
Conclusion
We uphold the decision of the Acting Director of NIH to withhold the
continuation awards, based on our conclusions that the decision was (11)
based upon a fair process and adequate information, and that the
sanctions did not constitute an abuse of discretion on the part of NIH.
/1/ The National Heart, Lung, and Blood Institute is a major
component of the National Institutes of Health (NIH), which in turn is
one of several major components of the Public Health Service, Department
of Health and Human Services (DHHS). /2/ New regulations
provided the Board with jurisdiction over this case (respondent's
decision was formally sent to UCLA on January 19, 1982). 45 CFR Part
16, Appendix A, Paragraph C(a)(3) (1981). Even though UCLA is the
grantee as defined in 45 CFR 74.3, the respondent asked the Board to
consider an appeal by the principal investigator in this case, if UCLA
concurred in the appeal, and the Board agreed to do so. The principal
investigator subsequently did appeal to the Board, and UCLA has
concurred in his appeal, agreeing to be bound by the Board's decision.
/3/ These NIH Guidelines were published at: 41 Fed. Reg. 27902, July
7, 1976 and amended at 43 Fed. Reg. 60080, December 22, 1978; 44 Fed.
Reg. 21730, April 11, 1979; 44 Fed. Reg. 42914, July 20, 1979; 45 Fed.
Reg. 6718, January 29, 1980; and 45 Fed. Reg. 77384, November 21,
1980. /4/ The appellant used ULCA-administered funds
(nonfederal) to perform the experiments, and also used NIH support for
the initial phases of the experiments. Thus he was sponsored by UCLA in
these experiments, and NIH supported a portion of them. /5/ In
addition to the constructive notice the appellant received through
publication of the Guidelines in the Federal Register, the preamble to
the Guidelines indicated that the Guidelines were sent to more than
25,000 NIH grantees as well as professional societies and medical and
scientific journals. 41 Fed. Reg. 27902. /6/ The appellant applied for
the grant about the same time (June 27, 1980) that he performed
the experiments in Italy and Israel. By the time the respondent made
its findings, the grant had been awarded and was in its first year of
operation. /7/ The appellant's application to NIH for the grant
which was later awarded and is the subject of this appeal proposed
neither human experimentation nor recombinant DNA research. In that
application, the appellant stated: Insofar as the design of such
experimental therapies in man must await the results of the detailed
series of experiments contained in this proposal, we have chosen
//ot to include any experiments involving therapy of human patients in
this proposal. . . . (Respondent's submission, Tab C, p. 74, record of
NIH Ad Hoc Committee's investigation) /8/ The other Institutes
that had awarded grants to the appellant considered the recommendations
made by the Ad Hoc Committee and placed conditions on those grants based
on the recommendations. In particular, the National Cancer Institute
decided to review his grants again in six months in light of the
problems associated with his research. /9/ Many of the circuits
have addressed the issue and applied the same principle. Willy's
Grocery v. U.S., 656 F.2d 24 (2d Cir. 1981); Collazo v. U.S., 668 F.2d
60 (1st Cir. 1981); Noell v. Bensinger, 586 F.2d 554 (5th Cir. 1978);
Nowicki v. U.S., 536 F.2d 1171, 1177 (7th Cir. 1976); Fuhrman v. Dow,
540 F.2d 396, 398 (8th Cir. 1976); General Securities Corp. v. SEC, 583
F.2d 1110 (9th Cir. 1978); Barnum v. National Transportation Safety
Board, 595 F.2d 869 (D.C. Cir. 1979). Due process on the issue of
sanction requires that the punishment follow rationally from the facts,
be authorized by the statute and regulations, and aim toward fulfillment
of the Act's purposes. Cross v. U.S., supra, at 1217. /10/
Although the grant was not yet awarded at the time the appellant
performed the experiments in Israel and Italy, the respondent was
authorized to withhold the continuation awards because of his previous
actions. 42 CFR 52.6(2) (1980) stated, in part: . . . Decisions
regarding continuation awards and the funding level of such awards will
be made after consideration of such factors as the grantee's progress
and management practices, and the availability of funds. In all cases,
continuation awards require a determination by HHS that continued
funding is in the best interest of the government. The appellant had no
grant which specifically provided for this type of human experimentation
or for any type of recombinant DNA research. If he had, he would have
received approval from UCLA and NIH to perform the research. The point
is that he had no approval from either entity to perform the
experiments, even though they supported the work. The only recourse
available to the respondent was to deny funding for related research.
OCTOBER 22, 1983