n060  1408  25 Oct 83
BC-DOCTOR'S-WORLD 3takes
(ScienceTimes)
By LAWRENCE K. ALTMAN, M.D.
c.1983 N.Y. Times News Service
    SALT LAKE CITY - Nearly a year after Dr. Barney B. Clark was rushed
to the University of Utah Medical Center for an artificial heart
implant, and seven months after his death, a moratorium is in effect
on the implanting of the device in a second human.
    The anguish of seeing several sick applicants die while waiting for
a chance to receive an artificial heart has led Dr. William C.
DeVries, the surgeon who did the first implant, to stop taking
further applications until the moratorium is lifted by the
university's institutional review board.
    Even prisoners on death row and a healthy 60-year-old woman who
wanted to donate her body to help mankind are among those who have
wanted to volunteer for the artificial heart experiment. They were
rejected because the benefits would not have outweighed the risks,
DeVries told a recent conference on the ethics of the artificial
heart held at Alta, a nearby ski resort.
    Although private funds are assured for at least two more artificial
heart experiments - the first cost more than $250,000 - members of
the artificial heart team and university officials who spoke in
interviews cited a number of reasons for the moratorium, including
these:
    -The University of Utah Medical Center's Institutional Review Board
(IRB), created by federal mandate as a result of the climate of
ethics that now guides medical research in every hospital where
government-supported experiments are conducted on humans, has not
authorized another transplant.
    -Delays have been attributed to the politics, personality
differences, inefficiencies and communication gaps that are part of
life in academia and other bureaucratic organizations.
    -The turnover of faculty that occurs normally in all medical schools
has affected the University of Utah's artificial heart team.
    -Many people feel uneasy about the growing links between academia
and industry, such as those that led to the creation of Kolff Medical
Inc., a spinoff from the University of Utah's artificial organs
program. The university owns 5 percent of Kolff Medical, and the
company is financing some of the research at the university.
    Why has the artificial heart research caused such institutional
deliberation and anguish, and attracted such public attention? Beyond
the obvious drama of the story, the mystique that has attached to the
human heart throughout history and the fascination with technology,
there is enormous potential significance.
    In mere numbers, heart disease is the nation's No.1 killer, far
ahead of cancer. If the Jarvik 7 artificial heart or an improved
version proves clinically successful, and Kolff Medical's ambitions
make that a possibility, such a heart could quite literally give new
life to many patients and their families.
    However, the financing of medical care and research for Americans
has changed drastically in recent years. Now, most costs are borne by
the taxpayer. Thus, the application of new therapies no longer is
strictly a private medical problem, but also involves thorny social,
economic, ethical and political factors. Few medical developments
combine those elements in a more vivid way than does the artificial
heart, and in few or none is the price of error so high, or the
urgency to get everything right the first time more pressing.
    Approval for another implant must come from the university's
institutional review board. None of the officials interviewed said
they knew when that permission would come, or how long afterward it
would take the team to select a new patient. The entire process could
take another three to six months, according to Dr. Chase N. Peterson,
the president of the university.
    But, meanwhile, Kolff Medical has raised $22 million to further
develop the artificial heart and an artificial ear. Kolff Medical has
also contracted with the two largest hospital chains in the United
States to train doctors to implant the artificial heart in animals,
and has taken preliminary steps to gain permission to do implants in
humans.
    At the same time, members of the Utah artificial heart team are
multiplying artificial heart experiments in animals. The seven
animals now living with artificial hearts here comprise the largest
such group ever, according to Dr. Don B. Olsen, the veterinarian
member of the team.
    A new, longer and thinner model of the artificial heart, called the
Utah 100, was implanted in the smallest calf ever to receive an
artificial heart earlier this month. Last week, Olsen implanted an
artificial heart in a 3-month-old calf with heart disease, in what
was only the second time that the Utah team had experimented on a
sick animal.
    Although moratoriums have been common in medical research, the one
on the artificial heart is surprising. Throughout the 112 days that
Clark lived on a Jarvik 7 artificial heart, University of Utah
officials repeatedly said that, subject to review board approval,
they planned to do another implant in a human within ''a few weeks.''
    Although the review process has taken longer than expected, Peterson
said, ''that doesn't bother me because the time frame is not the
issue.''
    Peterson called it ''a useful pause'' because ''this is such a
conspicuous case internationally as well as on our campus that the
IRB has been understandably cautious'' in considering approval for
the second case. The university, Peterson said, ''has leaned over
backward not to impose itself on the IRB because we have not wanted
to give any appearance of pressure.''
    (MORE)
    
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n065  1459  25 Oct 83
BC-DOCTOR'S-WORLD 1stadd
NYT SALT LAKE CITY: of pressure.''
    According to Dr. Ross Woolley, who headed the review board's
subcommittee on the artificial heart, ''the delays are really
bureaucratic.''
    Woolley said the review board and the artificial heart team had
allowed the moratorium because ''there is a lot of cranking up that
has to happen'' before another implant is done. He added that ''the
surgeons, nurses, administrators and everyone else involved have to
be psychologically geared and ready to go, and people don't
appreciate how long that process can take.''
    Despite all the advanced drills that preceded Clark's operation,
Woolley said, the case ''took a whole lot more out of people as
people than anyone had imagined it would. It was a stressful time and
a very powerful emotional experience for everyone.''
    The Food and Drug Administration has approved seven artificial heart
implant operations, each one subject to prior approval by the
university review board on a case-by-case basis.
    The board's basic purpose is to protect patients and healthy
research volunteers from overzealous medical investigators and from
poorly designed studies. The board achieves that goal in part by
examining the process by which medical researchers obtain informed
consent from volunteers.
    The university's review board is made up of 16 physicians, nurses,
pharmacists, lawyers, philosophers and lay community leaders. Some
sources contend that inevitable personality differences and
jealousies among members of the review board and the heart team have
played a part in the delay but only a small one. The board meets
regularly to approve or reject all proposals to experiment on humans
at the University of Utah, and it considers about 30 such proposals
at each monthly meeting, according to Dr. John A. Bosso, a pharmacist
who is chairman of the board.
    Since Clark's death, the board has met six times in closed sessions
devoted solely to the artificial heart research without reaching any
decision about a second case. Woolley's panel has met many more times.
    The reason for special meetings on the artificial heart is to avoid
delaying the work of other university researchers because of the
extraordinary complexity of the artificial heart program, Bosso said.
    Although the review board accepted a report on Clark's case from
Woolley's subcommittee last June, Bosso said, ''it wasn't enough
information'' to give a go-ahead for the second case.
    Bosso also said that when the review board then asked DeVries to
comment on the panel's report, the surgeon sent instead a revised
scientific protocol, which the board rejected. Bosso then wrote
DeVries again, asking for further data.
    Bosso added that ''we have never received the full report on the
first patient,'' which DeVries had agreed to submit. ''That's been a
holdup all the way along,'' he said. But Bosso acknowledged that the
board may have been less than perfectly clear in defining how
extensive a report it wanted from DeVries.
    At a review board meeting that DeVries attended last month, Bosso
said, ''We outlined what we needed and in what detail. We are now
waiting for that report. The ball is in Dr. DeVries's court.''
    That meeting was the only time DeVries met with the review board
since Clark's death. Most of the board's communications with DeVries
have been through exchanges of correspondence.
    DeVries declined to discuss his dealings with the board until it
makes its decision about the second case.
    Several sources said the moratorium was partly a result of confusion
arising from the correspondence.
    Bosso acknowledged that the process had been much slower than
expected and attributed blame for the delays ''to both sides.'' He
added, ''We probably didn't employ the right data-gathering
techniques, and Dr. DeVries's group hasn't supplied us with what we
have been asking for.''
    Woolley's subcommittee report on the Clark case was based largely on
his role, assigned by the board, to ''monitor'' how the artificial
heart team obtained informed consent, and whether it followed the
approved research protocol. It was an unusual task because most
review boards do not assign monitors, although some occasionally
conduct spot-checks of researchers's projects.
    Woolley's role became controversial because he spent up to four
hours each day with Clark. At one point he accepted an invitation to
join the artificial heart team as its ethicist. Woolley said he still
serves on the review board but does not vote on the artificial heart
program.
    Bosso said that had he known how deeply involved Woolley would
become, ''then Ross would not have been the monitor just because it
muddies the waters at this point.''
    According to the Hastings Center, a research organization in
Hastings-on-Hudson, N.Y., there are at least 550 such boards in this
country. Most observers agree that there is considerable variation in
the way they work.
    Dr. Albert R. Jonsen, an ethicist at the University of California
Medical School at San Francisco and an architect of the institutional
review board system, said at the Alta conference that a decade ago
national commissions had ''backed off defining a number of the
issues'' that had troubled the review board at the University of Utah.
    Jonsen said the commission had resisted ''strong pressure to come
out with very elaborate rules, regulations and procedures for IRBs''
because it was premature to do so. He said it was time to re-evaluate
the roles of review boards because the Utah board was ''asked to fly
a 747 with Wright Brothers parts.''
    (MORE)
    
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n069  1530  25 Oct 83
BC-DOCTOR'S-WORLD 2dadd
NYT SALT LAKE CITY: Brothers parts.''
    Institutional review boards were created in part to help deal with
one of the most difficult problems in medical research: selecting the
appropriate time, if ever, to intervene with experimental techniques
in the case of a patient suffering from an incurable and fatal
illness. It is a judgmental problem, deciding whether the potential
benefits outweigh the potential risks in an individual case.
    In general, the chances of success are best when the patient is
relatively healthy and the disease is in its early stages. But it is
then that the risk of ending life prematurely if the experiment fails
is greatest.
    In any case, selecting a healthy person to receive the artificial
heart would be ethically unacceptable to most Americans because there
would be little potential benefit to the volunteer. That is why
DeVries said he rejected death row prisoners and a healthy
60-year-old woman as volunteers.
    While there is a moratorium at the University of Utah, officials
across town at Kolff Medical are working toward implanting artificial
hearts at hospitals elsewhere in the country.
    Dr. Robert K. Jarvik, the 37-year-old president of Kolff Medical,
observed that the company had developed a more aggressive approach
with the artificial heart than had the University of Utah, for
business reasons as well as because ''patients are dying'' for lack
of this device.
    There are ''no insurmountable barriers to broad-scale application''
of the artificial heart, Jarvik said, adding that the goal of using
the device in hospitals was less a scientific research project than a
developmental program.
    Organizing and training regional teams in the use of the artificial
heart would be an essential step before it could be implanted in
everyday medical practice, Jarvik said. ''So it is very important,''
he continued, ''that we move beyond Utah and get away from the
umbrella of the highly experienced group at the University of Utah
and that we prove to be successful in transferring that technology
and know-how.''
    Toward that goal, Kolff Medical is working with the two largest
commercial hospital chains, Hospital Corporation of America and
Humana Inc. Both companies are shareholders in Kolff Medical, and
they are expected to bear much of the experimental and training costs
for the artificial heart team members in their chains.
    It would take at least another year and a half before an artificial
heart could be implanted in one of these centers, Jarvik said.
Further, he said, it would take at least five years for the Food and
Drug Administration to remove the experimental limitations and to
approve the device for more general use. That decision would be based
on the results of the experiments in the interval.
    
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