Dick: More fill on Glenn bill.....

On Wed, 12 Feb 1997 09:56:33 PST, Research
Administration Discussion Group wrote:

>I've attached the _lengthy_ comments by Glenn
from the Congressional
>Record, on his introduction of S.193.  Sorry if this
is overkill, but I
>thought the comments were very interesting.
>
>sheri alpert
>
>
>---------------------------------------------------------------
>
>CONGRESSIONAL RECORD
>Statements on Introduced Bills and Joint
Resolutions (Senate
>- January 22, 1997)
>
>[P:  S646]
>
>   By Mr. GLENN:
>
>   S. 193. A bill to provide protections to
individuals who are the human
>   subject of research; to the Committee on Labor
and Human Resources.
>
>  HUMAN RESEARCH SUBJECT
PROTECTION ACT
>
>   Mr. GLENN. Madam President, I rise today to
introduce the Human
>   Research Subject Protection Act of 1997. I send
the bill to the desk.
>
>   The PRESIDING OFFICER. The bill will be
received and appropriately
>   referred.
>
>   Mr. GLENN. Madam President, if I approached
any Senator here and I
>   said, `You did not know it, but the last time they
went to the doctor
>   or went to the hospital, your wife or your
husband or your daughter or
>   your son became the subject of a medical
experiment that they were not
>   even told about. They were given medicine,
they were given pills, they
>   were given radiation, they were given
something and were not even told
>   about this, were not even informed about it, yet
they are under some
>   experimental research that might possibly do
them harm-- maybe some
>   good will come out of it, but maybe it will do
them harm also--but
>   they do not know about it,' people would laugh
at that and say that is
>   ridiculous. That cannot possibly happen in this
country.  Yet, that
>   very situation is what this piece of legislation is
supposed to
>   address.
>
>
>   I have been in public life and have served this
country for many
>   years. Frankly, I do not think too many things
that I see surprise me
>   anymore about our laws and about
Government. Three years ago, though,
>   I began to learn about a gap in our legal
system that does truly
>   concern me. In 1993 the Governmental Affairs
Committee began to
>   investigate the cold war radiation experiments.
These experiments are
>   one of the unfortunate legacies of the cold war,
when our Government
>   sponsored experiments involving radiation on
our own citizens without
>   their consent. They did not even know the
experiments were being run
>   on them. It was without their consent.
>
>   One of the most infamous of these experiments
took place in my own
>   State of Ohio, when scores of patients at the
University of Cincinnati
>   were subjected to large doses of radiation
during experimental
>   treatments, without their consent, without their
informed consent.
>   During the course of this investigation, I began
to ask the question,
>   what protections are in place to prevent such
abuses from happening
>   again? What law prohibits experimenting on
people without their
>   informed consent?
>
>   What I found, when I looked into it, is there is no
law on the books
>   requiring that informed consent be obtained.
More important, I believe
>   there is a need for such a law, as there continue
to be cases where
>   this basic right--I do view it as a basic right--is
abused. As I
>   started out, I would like to put this on a personal
level for everyone
>   of my colleagues. You just think about your own
family, your own son,
>   your own daughter, or grandchildren who might
be, the next time they
>   go to a doctor, the subject of some medical
experiment that they are
>   not even told about. I do not think there can be
many things more
>   un-American than that.
>
>   With the introduction of this bill today I hope to
begin the process
>   of correcting some serious gaps in our legal
system. I want to make
>   clear right now I am not seeking to bring
medical research to a
>   screeching halt. Please do not anybody at NIH,
or anybody doing
>   research throughout this country, think we are
trying to stop that. We
>   are not. That is not my intent and not the intent of
this bill.
>
>   This country has the very finest health care
system in the world, in
>   part because of basic research. In fact, in large
part because we have
>   put more effort, more resources, more of our
treasure into health
>   research than any other nation in this world. In
fact, I believe most
>   people are not opposed to participating
themselves in scientific
>   research, if they are told about the pros and the
cons.  That is the
>   goal of this legislation, to make sure that
people have the
>   appropriate information to make an informed
choice about their medical
>   treatment.
>
>   Everyone listening today probably has heard
of the Nuremberg Code.
>   That is the list of 10 ethical research principles
which were produced
>   as part of the judgment against Nazi physicians
who engaged in truly
>   heinous medical experiments during World
War II.
>
>   The first principle of the Nuremberg Code
states that the voluntary
>   consent of the human subject of research is
absolutely essential.
>   Unfortunately, as we look back through our
history since the late
>   1940's, it appears that researchers in America
may not have taken all
>   that Nuremberg lesson completely to heart.
>
>   I ask my colleagues what the following names
might have in common:
>   thalidomide, Tuskegee, and Willowbrook?
>
>   Well, the answer is that these are all sad
examples of unethical
>   research conducted in the United States, and in
the United States well
>   after the Nuremberg Code was issued,
adopted and worldwide attention
>   had been focused on some of the abuses of
that time during World War
>   II.
>
>   Given this history, I find it astounding that even
after Nuremberg,
>   the thalidomide babies, Willowbrook,
Tuskegee and the cold war
>   radiation experiments, and who knows how
many other cases, we still
>   don't have a law on our books requiring that
informed consent--those
>   two words, `informed consent'--be obtained
prior to conducting
>   research on human subjects.
>
>   I have had research conducted on me
because of my past activities
>   before I came to the Senate in the space
program and so on, but I knew
>   what was being looked at, what was being tried.
I knew the objectives
>   of it, and I was willing to do that. I was happy to
do it. But it was
>   informed consent that I had personally, and I
knew what I was getting
>   into and glad to do it.
>
>I think most people feel the same way. If they
know what they are
>   getting into and they feel there is a good
purpose to it, they are
>   willing to do it. But to do research on people
when they don't even
>   know what the research or the medicines or
>   the radiation is that is being tried on them, I think
is
>   unconscionable.
>
>   What it comes down to is there are no criminal
fines or penalties for
>   violating the spirit or the letter of that Nuremberg
Code that should
>   be the basis of all of our informed consent in
this country.
>
>   In fact, our own Constitution says, `The right of
the people to be
>   secure in their persons . . . shall not be
violated.'
>
>   So there is no explicit statutory prohibition
against improper
>   research. I must add that just because there is
no law on the books
>   does not mean there are no protections for
people from unethical
>   medical or scientific research.
>
>   These tragic incidents I have mentioned have
resulted in changes in
>   the way human research subjects are treated. I
don't want to
>   misrepresent this, because there is a very
elaborate system of
>   protections that have developed over the
years.  Unfortunately, though,
>   this system does have some gaps and, if
enacted, I believe this
>   legislation will close those gaps.
>
>   Let me briefly describe the system that is
currently in place.
>
>   Regulations governing the protection of human
research subjects were
>   issued by the Department of Health, Education,
and Welfare in 1974 and
>   may be found at part 46 of title 45 of the Code of
Federal
>   Regulations.
>
>   In 1991, 10 years after a recommendation of a
congressionally
>   chartered Presidential advisory board, 16 other
agencies adopted a
>   portion of this rule, a portion of the rule to apply
to research that
>   these agencies sponsored. And at that point,
these regulations became
>   known as the common rule.
>
>   The common rule requires research institutions
receiving Federal
>   support and Federal agencies conducting
research to establish
>   committees, and these are known as--the
shorthand version is
>   IRB's--Institutional Review Boards. Their job is
to review research
>   proposals for risk of harm to human subjects
and to perform other
>   duties to protect human research subjects.
>
>   The common rule also stipulates requirements
related to informed
>   consent, how researchers must inform potential
subjects of the risks
>   to which they, as study participants, agree to be
exposed.
>
>   It should also be noted that HHS regulations
contain additional
>   protections not included in the common rule for
research involving
>   vulnerable populations; namely, pregnant
women, fetuses, subjects of
>   in vitro fertilization research, prisoners and
children.  No other
>   Federal agency has adopted these additional
protections.
>
>   Several mechanisms have been developed
by HHS and research
>   institutions over the years to extend the
common-rule protections to
>   more people. For example, many, but not all,
research institutions
>   which receive some Federal support voluntarily
apply common-rule
>   guidelines to all research conducted at their
institutions.
>
>   Additionally, in order to receive approval for a
drug or device from
>   the Food and Drug Administration, a research
institution or
>   pharmaceutical company must comply with the
requirements of the common
>   rule as administered by the FDA.
>
>   In addition to the Federal regulations, most
professional medical
>   societies and associations have adopted
ethical codes of conduct
>   regarding research.
>
>   The first such ethical code, called the Helsinki
Code, was adopted by
>   the World Medical Association in 1964. So it
has been on the books for
>   a long time. Since that time, other prominent
organizations, like the
>   American Medical Association, the American
Society for Clinical
>   Investigation, and the American Federation of
Clinical Research have
>   also adopted such ethical codes.
>
>   Most recently, in October 1995, the President
exhibited, I believe,
>   strong leadership and established the National
Bioethics Advisory
>   Commission, NBAC. This had been a long time
coming. It had been
>   suggested, but no one had ever gone ahead
and done this, and the
>   President exerted the leadership and
established the NBAC.
>
>   Quite simply, the scientific and ethical issues
which the NBAC are
>   supposed to evaluate represent some of the
most important, some of the
>   most complex and controversial questions of
our time.  NBAC's input
>   will be critical to informed policymaking for both
the legislative and
>   executive branches.
>
>The two primary goals of NBAC are to, first,
evaluate the current
>   level of compliance of Federal agencies to the
common rule, and,
>   second, evaluate the common rule and advise
both the executive and
>   legislative branches on any changes that might
be needed to it.
>
>   I very strongly support the work of the NBAC but
recently have become
>   extremely concerned to hear that more than 15
months after its
>   establishment, the NBAC is still operating with a
volunteer staff. It
>   was my understanding that a number of
Federal agencies supported the
>   creation of the NBAC and agreed to back up
their support with
>   resources and staff. Some NBAC members
have stated in public meetings
>   that they are frustrated with the progress the
Commission is making
>   and attribute the slow pace to the lack of
resources.  Additionally,
>   the resource problem may be limiting the
number of meetings of the
>   Commission.
>
>   Further, if this problem is not resolved in the
near term, the
>   Commission may have to stop meeting
altogether. I sent a letter to the
>   President's science adviser a few days ago,
Dr. John Gibbons, to
>   express my concerns about this. Dr. Gibbons
was working to resolve
>   this funding problem, which I view as an urgent
priority.
>
>   I am very glad to announce--as a matter of fact,
it was just
>   today--that these groups in Government that
are interested in this had
>   a meeting under Dr. Gibbons' leadership, and
the $1.6 million that was
>   supposed to accrue from these different
agencies to be used by the
>   NBAC is now forthcoming. So the NBAC is now
funded so they can do the
>   job they were originally supposed to do.
>
>   We are very glad to say that has happened just
today, and I am glad it
>   happened today, just when I am introducing this
bill, because it looks
>   as though we now truly are moving to support
the NBAC that did not
>   receive the kind of monetary support, the kind
of funding that we
>   thought it was going to have when it was first
formed a year and a
>   half ago.
>
>   There are a number of existing mechanisms
that do protect human
>   research subjects today. In fact, in March of
1996, the GAO reported
>   to me that the testing protection system has
reduced the likelihood of
>   serious abuses from occurring. However, the
GAO also pointed out a
>   number of weaknesses and gaps in the current
system.
>
>   There are at least four areas, four major gaps.
>
>   First, not all agencies have adopted the
common rule, including
>   agencies that currently sponsor research
involving human subjects. The
>   Department of Labor and the Nuclear
Regulatory Commission are examples
>   of agencies that sponsor such research but
those agencies have not
>   adopted the common rule, which I think they
should have.
>
>   Second, the common rule's research is
voluntarily applied in many
>   cases. Most institutions which receive Federal
funds will voluntarily
>   apply the common rule to all research
conducted at their institution.
>   However, not all research institutions adopt this
policy.  And in any
>   case, if any improper research is discovered at
these institutions,
>   there are very few steps available to the
Federal Government to do
>   much about it.
>
>   Third, a private institution or a researcher who
conducts nonfederally
>   funded research or is not seeking approval of a
drug or device with
>   the FDA does not have to apply the principles
of the common rule to
>   its research. In other words, there is a huge
area of all the private
>   medical research out there that is not under the
common rule unless
>   they just choose themselves to just voluntarily
do it.
>
>   Fourth, no Federal agency, other than HHS,
has applied the additional
>   protections described in 45 CFR 46 for
vulnerable populations--pregnant
>   women and their fetus, children,  prisoners--to
>   their own research. So the purpose of this
legislation is to help
>   close the gaps that exist within the current
system for protecting
>   research subjects.
>
>   Well, is there really a problem out there?
>
>   Is this just a paper loophole that I am trying to
close?
>
>   Unfortunately, Mr. President, there are ongoing
problems with
>   inappropriate, ethically suspect research on
human subjects. It is
>   difficult to know the extent of such problems
because information is
>   not collected in any formal manner on human
research.
>
>    The Cleveland Plain-Dealer in my home State
of Ohio has recently
>   reported in a whole series of articles, after
much investigation of
>   this issue.  And I quote from them:
>
>[p. S647]
>   What the government lacks in hard data about
humans, it more than
>   makes up for with volumes of statistics about
laboratory animals.
>   Wonder how many guinea pigs were used in
U.S. research?  The
>   Agriculture Department knows: 333,379. How
many hamsters in Ohio?
>   2,782.
>
>   So we have all this data on animals and little on
human beings. I
>   would hasten to add that the guinea pigs the
Plain-Dealer refers to
>   are the four-legged kind too and not the guinea
pigs that are humans
>   being used for research.
>
>   The reason we know so much about the use of
animals in research is
>   that we have laws governing the handling and
treatment of them.
>
>   For example, the Animal Welfare Act requires
that certain minimum
>   standards be maintained when using animals
in research.
>
>   Let me give you some recent examples which
indicate why,
>   notwithstanding the common rule and the other
protections that are in
>   place, I think additional protections are needed
in statute.
>
>   In 1994-95, in an effort to explore the rights and
interests of people
>   currently involved in radiation research
conducted or sponsored by the
>   Federal Government, the Presidential Advisory
Committee on Human
>   Radiation Experiments conducted an in-depth
review of 125 research
>   projects funded by HHS, DOE, DOD, VA, and
NASA. According to the ACHRE
>   report:
>
>   Our review suggests that there are significant
deficiencies in some
>   aspects of the current system for the protection
of human subjects.
>
>   The ACHRE found that documents provided to
IRB's often did not contain
>   enough information about topics that are central
to the ethics of
>   research involving human subjects. In some
cases the committee found
>   it was difficult to assess the scientific merit of a
protocol based on
>   the documentation provided.
>
>   ACHRE's report states that some consent
forms studied by the committee
>   are--and I quote--
>
>   . . . flawed in morally significant respects, not
merely because they
>   are difficult to read but because they are
uninformative or even
>   misleading.
>
>   The report states further:
>
>   Our review also raises serious concerns about
some research involving
>   children and adults with questionable
decision-making capacity.
>
>   And the ACHRE concludes:
>
>   All told, the documents of almost half the
studies reviewed by the
>   committee that involved greater than minimal
risk [to the subject]
>   raised serious or moderate concerns.
>
>   That is a horrible indictment.
>
>   As I mentioned earlier, from December 15 to 18,
1996, the Cleveland
>   Plain-Dealer published a series of articles
entitled `Drug Trials: Do
>   People Know the Truth About Experiments.'
>
>   And I want to give credit to the people that
worked on that. Keith
>   Epstein, has covered Capitol Hill here and has
written much and done
>   much investigative reporting working on this, as
did Mr. Sloat,
>   S-l-o-a-t, Bill Sloat. Those two fellows worked
on this and did a
>   great job in pointing out some of the problems
that still exist. And
>   we have talked to them about some of these
things.
>
>   The Plain-Dealer uncovered a number of
disturbing cases, very
>   disturbing cases as a matter of fact, where
people were either unaware
>   of the fact that they were involved in research or
were not provided
>   full information about potential side effects of
research. The series
>   raises very serious questions about the
adequacy of our current system
>   of protecting human research subjects.
>
>   The Plain-Dealer found, for example, of `4,154
FDA inspections of
>   researchers testing new drugs on people
[since 1977] . . . more than
>   half the researchers were cited by FDA
inspectors for failing to
>   clearly disclose the experimental nature of their
work.'
>
>   Another serious finding in this series is that
researchers who receive
>   the most severe penalty by the FDA, being
designated `Disqualified
>   Investigators,' have little fear of this fact being
found out by their
>   peers or patients. One of the articles discusses
potentially serious
>   problems in the way research conducted
outside of the United States is
>   incorporated into applications for drug
approvals in the United
>   States.
>
>The Plain-Dealer uncovered much evidence to
suggest that the Federal
>   Government continues to sponsor research
where informed consent is not
>   obtained. And this fact disturbed me greatly
also.
>
>   On November 14, 1996, the Wall Street Journal
published an article
>   that examined the practice at one
pharmaceutical firm, Eli Lilly and
>   Co. in using homeless alcoholics in their clinical
trials. The article
>   raises some disturbing questions about the
quality of the phase I
>   trials conducted by this one company. Also
serious ethical questions
>   are raised concerning the appropriateness of
paying homeless
>   alcoholics significant sums to be human guinea
pigs. It is not clear
>   from the article whether these tests were
reviewed by any IRB.
>
>   On December 27, 1996, the New York Times
reported on a New York State
>   appeals court ruling which found that the State's
rules governing
>   psychiatric experiments on children and the
mentally ill were
>   unconstitutional. The court found that the rules
did not adequately
>   protect people who, because of age or illness,
cannot give informed
>   consent to take part in drug tests or other
experiments. The article
>   mentions 10 to 15 of the 400 psychiatric
experiments covered by the
>   ruling as being `privately financed' and
therefore outside the
>   coverage of Federal rules.
>
>   How would you like it if your father, mother, son
or daughter,
>   husband, wife was in one of those institutions
and was having
>   experiments conducted on them without your
knowing about it or without
>   them knowing about it? That is what we are up
against.
>
>   On August 15, 1994, the New York Times
reported on ethical and legal
>   questions regarding a company's efforts to
promote a drug that can
>   make some children grow taller than they
otherwise would.  The drug in
>   question, Protropin, has been approved by
FDA for use in children
>   whose bodies do not make sufficient quantities
of human growth
>   hormone. However, once approved, doctors
may prescribe it for other
>   purposes at their discretion. In this case the
company was apparently
>   surveying schools for short children and then
trying to funnel those
>   children to doctors who would prescribe the
drug whether or not the
>   children lacked the human growth hormone.
This unapproved research was
>   occurring without the oversight of an IRB. And at
least 15,000
>   children have taken this drug.
>
>   Another illustration of the precarious coverage
of the common rule
>   occurred in 1995 when it became known that
researchers from the Center
>   for Reproductive Health at the University of
California Irvine, were
>   fertilizing humans and implanting theses in
different mothers without
>   the consent of the donor. This research was not
being funded by any
>   Federal agency; however, NIH was funding
more than $20 million worth
>   of other research at the university. Even though
several internal and
>   external investigations by the university and the
district attorney
>   were being conducted on this experiment, a
clarifying moment occurred
>   when investigators from OPRR visited UC
Irvine early last year. These
>   investigators reminded university officials of the
common rule;
>   the fact that the university had agreed to apply it
to all research
>   conducted there--through OPRR's assurance
process; and that NIH was
>   currently funding a good deal of research at the
institution. Within a
>   week of OPRR's visit, the university took public
action to halt the
>   research and formally investigate the
researchers.
>
>   On October 10, 1994, the New York Times
reported on a New York doctor
>   who adopted two types of drugs approved by
FDA for cancer treatment
>   and stomach ulcers for an unapproved use to
perform nonsurgical
>   abortions. The article quotes the doctor saying
that in 121 of 126
>   cases his approach was successful. The
remaining five cases required
>   surgery to complete the procedure. Because
the drugs were FDA approved
>   and the doctor was not funded or connected to
federally sponsored
>   research, no IRB or approved informed
consent procedures were
>   required. Apparently, each patient signed a
three-page consent form,
>   but this was not approved by an IRB. According
to the Times, once FDA
>   approves a drug, physicians are generally
allowed to use it for off
>   label purposes.
>
>Now Mr. President, some of the issues
discussed in these articles are
>   problems with how the common rule itself is
being applied. Some of
>   these examples illustrate the gaps in the
common rule coverage. My
>   legislation will address both the coverage and
the application of the
>   common rule.
>
>   Now how precisely would the legislation work?
>
>   It would require all research facilities to register
with HHS.
>   Registration shall include: First, statement of
principles governing
>   the research facility in its conduct of human
subject research;
>   second, designation of the official responsible
for all human subject;
>   third, designation of membership roster of
IRB(s); and fourth,
>   attestation that the research facility is
complying with the
>   protection requirements of the common rule.
>
>   The legislation includes a grandfather
provision for all research
>   entities which currently have negotiated project
assurances with HHS.
>   The vast majority of research facilities have
such assurances.
>
>   The legislation contains a 3-year reregistration
requirement.
>
>   The legislation includes criminal penalties for
failure to comply with
>   the act. Therefore, if enacted it would be a
felony offense to
>   experiment on someone without their informed
consent.
>
>   The intent therefore of this legislation is twofold:
First, to fill in
>   the gaps of coverage of the common rule by
requiring all research
>   involving human subjects to abide by the rule;
and second, to elevate
>   the importance of conducting research
ethically, the bill provides
>   criminal fines and penalties for failure to comply
with the
>   requirements of this law, and by extension 45
CFR 46.
>
>   Finally Mr. President, my legislation would
codify a recommendation
>   which the Advisory Committee on Human
Radiation Experiments made
>   regarding the conduct of classified research
involving human subjects.
>
>   Specifically, the advisory committee
recommended that informed consent
>   of all human subjects of classified research be
required, and that
>   such requirement not be subject to waiver or
exemption.  Under current
>   rule and executive order, it is possible to waive
informed consent and
>   IRB review for classified research. Title II of this
legislation would
>   prohibit the waiver of either informed consent or
IRB review for
>   classified research.
>
>   The advisory committee also recommended
that human subjects of
>   classified research be provided with certain
information regarding
>   that research. My legislation would require that
such subjects be
>   information concerning: First, the identify of the
sponsoring Federal
>   agency; second, a statement that the research
involves classified
>   information; and third, an unclassified
description of the purpose of
>   the research.
>
>   Mr. President I have tried today to briefly lay out
the case for the
>   need for the legislation I am introducing. I know
that my colleague
>   from Ohio, Senator DeWine, is also concerned
about the issues I have
>   raised today, and about those that appeared
last month in the Plain
>   Dealer. I believe that he has requested that the
chairman of the Labor
>   and Human Resources Committee hold
hearings on this subject. I think
>   that is entirely appropriate. And I hope that this
legislation could
>   be considered in that process. I look forward to
working with the
>   Labor Committee in this regard.
>
>   I do not claim to have the magic bullet solution
with this bill.
>   However, I believe there are some key
principles which should guide
>   the Senate's consideration of this legislation.
These principles are:
>
>   First, informed consent and independent review
of experiments
>   involving human subjects must be required.
>
>   Second, anyone who violates the right of
research subject to have
>   informed consent, should be held criminally
responsible for that
>   violation.
>
>   I want to put this in personal terms once again.
You can imagine your
>   spouse, husband, wife, father, mother, children,
being experimented on
>   without your knowledge or their knowledge.
That is unconscionable, and
>   we should not permit that. This legislation will
close many of the
>   loopholes that permit that to happen now.
>
> As the legislative process moves ahead, it is
certain that the bill
>   will undergo scrutiny and amendments. But I
think the outcome, if this
>   legislation is enacted into law, will be improved
protections for all
>   Americans.
>
>   Madam President, obviously, I welcome any
cosponsors on this
>   legislation. I will be sending out a `dear
colleague' letter to all
>   the offices, and I hope we get a good response
to that. I think there
>   are very few Senators who will not back this
when they hear what can
>   happen then to them, their families, and their
constituents back home,
>   if we do not pass something like this.
>
>   I think this is many years overdue. I don't want
to scare people to
>   death with this, because I think most of the
research in this country
>   is conducted in a way that is good and is with
informed consent--in
>   most cases. But just the few examples that I
have mentioned here
>   today, as well as the articles in the Cleveland
Plain Dealer and New
>   York Times I quoted from, indicate there is still
a very major problem
>   in this area and one that we want to close the
gaps on so that no
>   American is subjected to experiments like this,
unless they know
>   exactly what is going on and have given
informed consent.
>
>   Thank you. I yield the floor.