Fourteenth ACOT
Meeting
Crowne Plaza
Silver Spring, MD
November 15-16, 2007
November 15, 2007
Welcome
& Introductions
Remy Aronoff
announced that five ACOT members could not attend this meeting.
He announced that Mary Kelleher-Crabtree is a new member on
the committee. Ms. Kelleher-Crabtree is a pancreas recipient
and is currently also a candidate. She works in the DC area
with MMG, a health communications company, in the health care
practices division. She also develops written guides and educational
programs for individuals who are considering enrolling in
clinical research studies. She has served as a consultant
to clinical studies seeking to recruit potentially vulnerable
subjects. Ms. Kelleher-Crabtree has also worked at NIH, for
NIAID.
In another announcement, he said that this may or may not
be Gail Agrawal’s last meeting. Papers have been submitted
extending her position as Chair, but approval has not yet
been received to do so. This is, however, Mr. Aronoff’s
last meeting as the Executive Secretary because he will be
the Executive Secretary of the Advisory Council on Blood Stem
Cell Transplantation. Dr. Gregory Fant will replace him as
Executive Secretary of ACOT.
Dr. Fant
is a health statistician in the Health Resources and Services
Administration’s Division of Transplantation (DoT).
Dr. Fant serves as the project officer for the Scientific
Registry of Transplant Recipients (SRTR). He joined the Federal
Civil Service in 1997 and has served as a Federal statistician
for the HIV/AIDS Bureau, Walter Reed Army Medical Center,
U.S. Department of Defense, and the Bureau of the Census.
Dr. Fant earned his PhD at the University of Nebraska. Mr.
Aronoff will work with Dr. Fant in preparation for the next
ACOT meeting.
The meeting agenda was rearranged due to presenters’
scheduling needs.
Tissue Regulation Update
Sam Holtzman
confirmed that everyone had received a copy of the documents.
His workgroup held a conference call and has been discussing
tissue regulation issues. The workgroup members concluded
that it is hard to make any suggestions to ACOT about a direction
it should take in terms of making a recommendation to the
Secretary because the industry itself needs to sort through
these issues before ACOT can act. The Association of Organ
Procurement Organizations (AOPO) convened a task force on
public trust and tissue recovery. This task force has been
meeting and is in the process of formulating its final recommendations.
The American Association of Tissue Banks (AATB) and the Eye
Bank Association of America (EBAA) have been engaged in the
process, as have been a number of the major U.S. processors.
The workgroup determined that it is premature to come up with
a recommendation until ACOT members have a better idea of
what the industry itself is recommending in terms of internal
practices and regulations. It was Mr. Holtzman’s suggestion
to invite representatives from these groups to come to the
meeting today to present to the ACOT.
This group
of presenters included Tracy Schmidt, past president of AOPO,
who spoke to the group by telephone because of another commitment.
Robert Rigney from the American Association of Tissue Banks
(AATB) talked about AATB’s involvement in the process.
Lastly, ACOT heard from Dr. Laura St. Martin with the Food
and Drug Administration (FDA) about the new things FDA has
been doing for the last year.
P.
Robert Rigney, Jr., JD – The American Association of
Tissue Banks (AATB)
Mr. Rigney’s
stated that his goal is to address the ACOT’s concerns
raised at other meetings. He presented on what the AATB has
been doing, and also discussed the safety of tissue transplants
in the U.S.
At the
November 2, 2006, and on May 15, 2007, ACOT meetings, comments
were made that: “When something untoward occurs concerning
tissue in the United States, it affects organ donation rates
as well.” In theory, if this is true, then the reverse
is also true; tissue donation is affected by negative publicity
on organ transplantation. In the last few days, the tissue
community has had to answer questions about the Chicago case
(e.g., HIV transmission) and other issues about organ transplantations.
California Kaiser, St. Vincent’s, U.C. Irvine –
all of these places have had problems with organ transplantation.
We know that organ and tissue donations are increasing in
number. Negative publicity is not, in fact, having a dampening
effect on transplantation.
The statement
has been made that there is: “a lack of information
about tissue and recovery in the United States. It is not
clear what organizations are doing recovery…”
This is not true at all. The FDA requires regulation of all
tissue transplant facilities. There is a very searchable system
on the FDA’s webpage. There are three times more tissue
donors than there are organ donors. The Human Cell and Tissue
Establishment Registration System (HCTERS) indicates that
there are 138 active establishments that recover and/or distribute
ocular tissues; and there are 102 establishments that process
ocular grafts. Among active tissue establishments that work
with other tissues, the numbers are 158 that recover musculoskeletal
(MS) tissues; 95 that process bone and soft tissue (MS, OA);
75 that process skin (S); 47 that process heart valves (C);
and 580 that distribute conventional tissues.
Another
quote has been made about standards, namely that: “…it
is relatively easy to enter the field, which is not well-regulated
(e.g., there are no mandatory guidelines).” This is
also not true. Organizations might be able to register, but
the FDA will show up at their doors very soon. The FDA has
regulated tissue banks since 1993. Both Federal and State
statutory regulations apply to tissue organizations, and private
accreditation is provided by the AATB and EBAA.
Legal
and regulatory oversight includes Federal statutes, such as
the National Organ Transplant Act (NOTA) and the Public Health
Service Act, and regulations by the Food and Drug Administration
(FDA). The FDA’s 21 CFR 1270 & 1271 provide a
comprehensive system of regulations that includes registration
and product listing, donor eligibility, good tissue practices,
and guidance documents. Legal and regulatory oversight on
the part of the States include statutes such as the Uniform
Anatomical Gift Act (UAGA); registration and/or licensing
requirements; and other state-imposed requirements (e.g.,
New York). Private accreditation is handled by AATB and EBAA.
Federal
regulations have three basic elements: 1) registration, 2)
donor eligibility requirements, and 3) good tissue practices.
There are 14 guidance documents and an Standard Operating
Procedure (SOP) manual issued by the FDA on adverse reaction
reports. Mr. Rigney displayed the binders of FDA regulations
and guidance documents for tissue banks. FDA regulations in
21 CFR 1271 et seq. describe registration requirements (Subparts
A and B [1271.1 – 1271.37]; donor eligibility requirements
(Subpart C [1271.45 – 1271.90]); and good tissue practice
requirements (Subparts D [1271.145 – 1271.320]).
In fact,
tissue banking is heavily regulated clinically. Published
AATB standards include four guidance documents and seven changes
to standards that have been made just in 2007 alone. Administrative
and clinical regulations are both issues. Mr. Rigney noted
that the field is not highly regulated administratively; it
is, however, more clinically regulated than organ procurement
organizations.
The AATB
started as the Navy Tissue Bank, which had as its mission:
“To facilitate the provision of safe transplantable
tissues of uniform high quality in quantities sufficient to
meet national needs.” It establishes standards to prevent
disease transmission and to ensure optimum clinical performance
of transplanted cells and tissues. It also accredits tissue
banks in order to ensure compliance with AATB Standards. Certification
includes training and certifying tissue banking personnel.
The AATB
Standards Committee meets on a monthly basis and the 12th
edition of its standards will be published in 2008. The first
edition, in 1984, predated FDA regulation of tissues by 10
years. The AATB standards address all aspects of tissue banking,
including institutional requirements; records; informed consent;
donor suitability; retrieval; processing; containers; storage;
labeling; distribution; packaging; recalls; SOPs; staff; facilities;
equipment; QA; QC; testing; and release. The over 100 pages
include 55 Sections, 275 Subsections, and 3 Appendixes. The
AATB Standards Committee includes liaisons with many organizations
including the FDA, CDC, NY State Department of Health, EBAA,
ASTM, AAMI, AORN, and Health Canada. Twenty States cite AATB
in their State laws and/or regulations.
AATB Standards
are universally accepted industry standards. They are referenced
in statutes and/or regulations in more than 20 States. Six
States and the District of Columbia require AATB accreditation.
One State requires either AATB accreditation or FDA registration.
Two States have incorporated AATB Standards by reference (burn
centers may only obtain tissue from AATB-accredited banks).
In two States, recovery agencies must be AATB-accredited;
in two, tissue regulations must be based on AATB Standards.
One State requires that AATB Standards be followed, and one
State decrees the suitability of the gift is to be based on
criteria established by the AATB. In four States, technicians
must be AATB/CTBS or be certified by a tissue organization
that is accredited by AATB. In two States, tissue donations
must be tested for HIV and other communicable diseases as
specified by the AATB.
AATB’s
Standards have served as a model for many regulations and
other standards, including FDA’s CGTPs regulations;
Health Canada’s Cells, Tissues and Organs Regulations;
New York Department of Health’s Tissue and Cell Standards;
the European Union’s Commission Directives; the European
Association of Tissue Banks Standards; the Latin American
Association of Tissue Banks Standards; and the British Association
for Tissue Banking Standards.
The AATB
has four guidance documents and several others are being developed
right now. AATB guidance documents in development include
those on the following topics:
- Validation
and Qualification
- Audit
Tool for Inspecting Recovery Agencies
- Content
of Written Agreements
- Staff
Training and Competency Assessment
- Aseptic
Tissue Processing
- Physical
Examination of a Living Donor
- Uniform
Donor History Questionnaire
- Tissue
Donor Screening
- Consent/Authorization
- Adverse
Outcome Reporting & Investigations
- Communication
with Medical Examiners
- Communication
with Funeral Home Professionals.
Many organizations
recommend AATB accreditation. For example, the American Academy
of Orthopaedic Surgeons has a policy that it will use tissue
only from banks accredited by AATB. The American Burn Association
requires that burn center hospitals’ policies and procedures
for the use of allograft tissues must be in compliance with
all Federal, State, and JCAHO requirements and, when feasible
and appropriate, with standards of the American Association
of Tissue Banks. A Philadelphia Grand Jury Report issued a
recommendation to: “Require all tissue agencies to be
licensed by the State and accredited by the American Association
of Tissue Banks…Accreditation by the AATB should be
required for a license. This would automatically subject the
agencies to the most comprehensive standards for safe tissue
practices, including qualifications and training of staff,
procedures for donor consent, and donor eligibility screening
by medical professionals.”
There
are issues relating to tissue regulation. With Biomedical
Tissue Services (BTS), for example, there were charges of
allegedly forged consent forms, and allegedly falsified medical
records. BTS is not AATB-accredited. Donor Referral Services
(DRS) allegedly falsified medical records and is not AATB-accredited,
either. In response to the BTS case, the AATB appointed an
investigative task force of experts who conducted fact finding
and analysis, and made recommendations. The overall findings
of the task force were that AATB accreditation is important.
The problems centered on non-accredited tissue banks and,
in fact, it was AATB-accredited banks that reported the discrepancies
to the FDA and led to these (and other) disclosures. Another
finding was that AATB standards are critical – the tissue
banks in question had violated AATB standards and compliance
with the standards would have prevented the negative outcomes.
Finally, the task force noted that changes are needed to prevent
re-occurrence and potential criminal activity.
The AATB
decided to make changes to its standards to prevent this sort
of thing from happening again. With BTS, we realized that
good practices that one ought to be able to take for granted
cannot, in fact, be assumed to happen. Many changes in standards,
accreditation policies, and CTBS programs have stemmed from
this case. For example, around consent, AATB Bulletin No.
07-36, dated 4/24/07, requires the recording of all telephone
consents. It requires a sampling plan that verifies consent
documentation, requires an audit plan to compare content of
recording to paper documentation, and mandates that inspections
and audits include sampling requirement. These requirements
exceed the consent laws in every State.
Changes
were also made in AATB standards with respect to medical records.
AATB Bulletin No. 07-02, dated 1/9/07, requires information-sharing
of donor records. Changes include requiring that a certified
copy of the death certificate be included in donor records
if the death did not occur in a hospital; if no third-party
records are available to establish cause of death; or if an
autopsy was not performed (see AATB Bulletin No. 07-04, 1/22/07).
AATB now requires that only authorized and trained personnel
can obtain consent and perform risk assessment interviews.
In terms of recovery and collection, new standards require
that tissue recovery sites must be qualified using 12 AATB
suitability parameters (see AATB Bulletin No. 07-46, 7/10/07).
Additional
changes include that AATB inspectors must be allowed to inspect
non-AATB-accredited tissue banks that work with an accredited
facility. AATB’s Guidance Document No. 4 (Providing
Service to Tissue Donor Families), dated 3/10/07, requires
substantial proof of tissue donor family services program.
Additional Guidance documents are in process, as noted earlier.
There
is a new code of conduct in place that organizations have
to sign. The AATB can revoke their certification if this does
not happen. We argue often to colleague organizations, including
to the ACOT, in favor of supporting criminal sanctions in
this area. Anyone who falsifies medical records or falsifies
consent should be subject to criminal sanctions. This was
added to the UAGA in revision.
Turning
to the issue of the safety of tissue transplants, in the last
20 years there have been 10 million tissue transplants. The
last viral transmission was in 2002; the last case of HCV
was in the early 1990s; the last case of TB; and HBV was 50
years ago. The last case of HIV transmission was 20 years
ago and was in a person within the “window period”
for identifying the disease. There have been no reported cases
of LCMV, Chagas Disease, Rabies, or West Nile Virus among
tissue transplantation – these have only occurred in
organ transplantation. For NAT (HIV/1 and HCV), the AATB requires
NAT testing and has done so since 2005 (the FDA started requiring
this last summer). However, NAT testing is not yet required
for organ transplantation.
The bacterial
contamination death in 2001 occurred with a non-accredited
recovery agency/processor, the same one that was responsible
for the 14 cases of Clostridium. This processor is now accredited
by the AATB. There has been only one case of fungal contamination,
and no cancer transmissions from tissue transplantation. The
Human Tissue Task Force (HTTF) conducted a blitz and inspected
153 tissue recovery agencies in the first quarter of fiscal
year 2007. They found no “major inaccuracies or deficiencies
in records that could put tissue recipients at risk for transmission
of relevant communicable disease agents or diseases.”
To ensure safety, all of the following are required: safety
of tissue transplants; screening (we have extensive standards);
testing (NAT); donor eligibility (Medical Director); processing
(Validation); and final terminal sterilization (Irradiation).
In conclusion,
we know that donation rates are increasing for both organs
and tissues.
We do know a great deal about tissue banks both in terms of
their numbers and their activities. Tissue banking is heavily
regulated, and AATB-accredited banks distribute virtually
all of the tissue for transplant in the U.S. The field has
a 23-year history of proven standards -- with a mechanism
for continuous updating of these standards that are more detailed
and extensive than the FDA. The AATB has a 22-year-old accreditation
program to ensure compliance with its standards. These programs
have produced a remarkable safety record and are recognized
nationally and internationally. AATB accreditation is recommended
by medical organizations and others, and serves as an additional
check on safety.
In closing,
the tissue transplantation community asks the ACOT to include
them in any activities around tissues.
Ms. Agrawal
asked ACOT members to hold their questions because Mr. Schmidt
was on the telephone and the speakers would address questions
jointly after he spoke.
Tracy
Schmidt – Intermountain Recovery Systems
Tracy
Schmidt was asked to follow up on the efforts that began in
November 2006, to coordinate among organizations that are
involved with tissue transplantation. The goal of this effort
was to look at ways to improve trust in the tissue recovery
process and field. Many organ recovery agencies are involved,
as well.
In November
2006, a meeting was held that included organ recovery agencies,
the AATB, the EBAA, and others. This group prioritized areas
in which they can coordinate and improve public trust issues.
There is a lot of really great support for this effort. Mr.
Schmidt noted that handouts are available in the ACOT meeting
room. Areas of focus for the group include the following:
- Improving
communication (specifically about how to deal with crises);
- Documentation
to identify and explain the value of tissue donation (many
criticisms of the field concern money so the group wanted
to address this and also explain the process);
- Whole
body donation area and research (a subgroup created a document
that can be a resource for whole body issue);
- Minimum
quality standards and organizational structures to assist
agencies to do due diligence when looking for tissue recovery
partners (this includes how to get information about an
agency or organization before partnering with them);
- Donated
tissue labeling because many organizations document and
label different tissues in different ways and this should
be standardized as tissues are recovered, processed, transported
and used. In addition, this touches on the need to be respectful
and recognize it’s not just a commodity;
- Accreditation
(a subcommittee looked at different processes among the
various organizations) and surveying ways to handle accreditation
so that the process can be coordinated between agencies;
- Medical
examiner (ME) relationships in terms of what is required
of tissue recovery agencies with respect to MEs (a lot of
this has been solved by work done in Texas).
The group
worked on these areas. The group met three times and is looking
forward to doing more cross-organizational work in the future.
Mr. Schmidt’s colleague added that this was a good opportunity
for tissue processors and key agencies to talk about shared
issues. It’s not just about the single issue of tissue
recovery and public trust, but also includes issues connected
to donation as well. There are a lot of resources available
if ACOT members have questions.
Discussion
Ms. Agrawal
thanked the speakers and asked for questions from the ACOT
members.
Mr. Holtzman
asked Mr. Rigney about his statement that the FDA had inspected
153 recovery agencies. He also said that the AATB has accredited
over 100 and asked whether Mr. Rigney would describe the difference.
Are the 53 not accredited eye banks? In response, Mr. Rigney
said that his association accredits processing, storage, distribution,
recovery or any combination of those. The FDA tissue task
force was composed only of tissue recovery agencies. The extra
places visited were probably multiple sites and/or non-accredited
agencies. There are 59 OPOs and 58 are registered as tissue
establishments, but only 20 are accredited by AATB.
A participant
asked the FDA how many agencies that are recovering tissues
are not AATB-accredited. The answer was that they would have
to look it up. If Dr. St. Martin had to guess, she would say
it’s about 50. A suggestion was made to print the list
off of the FDA page and match it to the AATB-accredited list.
The speakers offered to do that and get back to ACOT members.
Mr. Holtzman
asked, given the presentation of the value of accreditation,
why ACOT should not recommend that every recovery agency be
accredited by the AATB? Mr. Schmidt responded that it’s
not a bad recommendation. He commented that there should be
an effort to improve coordination so that only one organization
has to do the accrediting, rather than multiple organizations.
Mr. Rigney added that he has made the same recommendation
before and the AATB would welcome it. It would go a long way
to ensuring the safety of tissue transplantation in the U.S.
Ms. Anita
Principe said she applauded the presentations. She commented
that she had spoken at an AATB meeting in the 1970s as part
of an effort to try to foster dialogue between organ and tissue
communities. She is confident that -- with this initiative
– this will be achieved. It’s important because
they are the same issues to the public. The difference between
administrative and clinical oversight is a good point to make.
It is her hope that coordination proceeds so that there is,
ultimately, oversight and regulatory accreditation for all
tissue banks. To the point that Mr. Rigney made about how
it is easy for an organization to register but it is hard
for them to do the work, in New York there have been problems
arising from the length of time it takes for non-accredited
tissue banks to be identified. Finally, it should be mandated
that these organizations be accredited from groups like the
AATB or the EBAA. She applauded these efforts and looks forward
to future progress.
Dr. Matthew
Kuehnert, ex officio member from the CDC, clarified a point
about rabies. The tissue that was transplanted was considered
“organ” not “tissue.” From the CDC
standpoint, however, it’s not really an organ, and they
are unsure what to call it. Rabies has been transmitted through
corneas, but it is important to recognize that it’s
hard to communicate risks to the public if experts themselves
do not understand what those risks are. Most tissues are processed,
so the risk is low. But the number of tissues being used is
high, which is where problems with tissue come from. For organs,
on the other hand, the risk is higher, but there are smaller
numbers being used. Thus, the risks between the two become
equivalent.
Dr. Jim
Burdick stated that he would like to quibble with the previous
speaker. To clarify, there is a HRSA regulation that vessels
removed with an organ for transplantation are to be used only
for organ transplantation. These vessels are regulated as
organs, as specified by Secretary. There is a clear process
for monitoring this, and a clear policy that specifies following
the vessels and determining where they go and ensuring that
they are discarded if not used in the organ transplant setting.
Whether there are cracks in the system – if tissues
are retrieved that are not at least secondarily covered, as
by AATB accreditation – that is another question. The
ACOT may not be the right place for this discussion but there
is some disquiet on this area and requiring accreditation
would make a big difference.
Dr.
Laura St. Martin – The Food and Drug Administration
(FDA)
Dr. St.
Martin provided an FDA update on Human Cells, Tissues, and
Cellular and Tissue-Based Products (HCT/Ps). She commented
that some of the presentation might be redundant after Mr.
Rigney’s presentation.
The FDA
has been regulating tissues since 1993 – limited scope,
limited spectrum of diseases. The interim tissue rule (21
CFR 1270) was published in December 1993, and finalized in
July 1997. It addressed donor suitability and included a limited
scope of tissues and diseases. The proposed approach was published
in February 1997 and opened for public comment. Input was
provided from other Federal agencies, including HRSA and the
CDC. The current “Tissue Rules” (21 CFR 1271)
became effective May 25, 2005. It takes a tiered, risk-based
approach and includes a broad scope of cells and tissues.
The regulations
on HCT/Ps cover: “Articles containing or consisting
of human cells or tissues that are intended for implantation,
transplantation, infusion, or transfer into a human recipient.
This includes musculoskeletal tissue, skin, ocular tissue,
human heart valves, dura mater, reproductive tissue, hematopoietic
stem/progenitor cells, other cellular therapies, and tissue/device
and other combination therapies.” The regulation has
several specific subparts, including Subpart A (scope and
definitions); Subpart B (procedures for registration and listing);
Subpart C (donor eligibility); Subpart D (current good tissue
practice); Subpart E (reporting and labeling); and Subpart
F (inspection and enforcement). Dr. St. Martin described each
in turn.
Subpart
A’s general provisions are to provide a purpose and
scope for all parts of the regulation. It also includes important
definitions.
Subpart
B is the procedures for registration and listing. Subpart
B has the force of law; it is a requirement. Any entity that
does the following activities must register: performs recovery,
processing, storage, labeling, or distribution of HCT/Ps,
or donor screening or testing. Organizations must register
and be listed within five days. They must also re-register
annually and update the registration if there are any changes
in location or ownership. All foreign establishments importing
HCT/Ps to the U.S. must register and list such HCT/Ps. As
of August 2007, there were 2,650 establishments registered,
of which 531 were inactive. Musculoskeletal/ocular was 1,286;
hematopoietic stem cell was 654; and reproductive organizations
were 685 of those registered. The number also includes 186
international establishments (mostly stem cell entities).
Subpart
C concerned donor eligibility and sets forth procedures for
eligibility determination including the need for an interview
for high-risk behaviors, a physical exam, and screening and
testing for relevant communicable diseases. HCT/P must not
be administered until the donor has been determined to be
eligible, with some exceptions. Sub-part C is very specific
about what is required and also includes detailed recommendations
on how to conduct donor eligibility activities. These must
be completed before tissue is used, with only some exceptions.
Subpart
D describes current good tissue practice, specifically the
methods, facilities, and controls for manufacturing to prevent
communicable disease transmission. It includes broad goals
that are applicable to the wide range of HCT/Ps. It requires
a quality program to prevent, detect, and correct deficiencies
that could increase communicable disease risk.
Additional
requirements are set forth in Subpart E, including adverse
reaction reporting, and labeling requirements. Organizations
must report significant adverse reactions for their products.
The FDA then determines if further action is necessary. The
FDA may also issue more recommendations based on reporting.
Subpart
F describes inspection and enforcement activities. Establishments
must permit the FDA to inspect all manufacturing locations,
and the inspections are usually unannounced. The frequency
of inspections is at the FDA’s discretion. Enforcement
actions include an untitled letter, a warning letter, an Order
of Retention and Recall, and an Order of Cessation of Manufacturing.
Enforcement actions will depend on the violations. Dr. St.
Martin showed a slide indicating the number of inspections
conducted by the FDA. The number inspected has increased over
time; the FDA is looking at ways to improve its inspection
capabilities.
The FDA’s
Human Tissue Task Force was formed in August 2006 to evaluate
and strengthen the FDA’s risk-based system for regulating
HCT/Ps; to assess the challenges that had occurred in implementation
of the new system; and to identify additional steps to further
protect the public health by preventing the transmission of
communicable disease while assuring the availability of safe
products. The Task Force report issued in June 2007 is available
at the FDA
website.
In terms
of inspections and compliance activities, from October 1,
2006 through March 31, 2007, the FDA conducted 153 inspections
of domestic musculoskeletal recovery establishments. Although
deviations from the regulations were noted during some of
the inspections, no major inaccuracies or deficiencies were
observed. None of the inspections resulted in regulatory action.
Some guidances
have been issued, and others are in the works. A draft CGTP
guidance is in progress. The FDA published a guidance for
the industry to aid with compliance with 21 CFR 1271.150(c)(1),
in September 2006. Cord Blood Guidance was released in January
2007. A guidance on HCT/Ps from Donors Tested Using Pooled
Specimens or Diagnostic Tests, was also released in January
2007. A Donor Eligibility Guidance was reposted in August
2007.
The Advisory
Committee on Blood Safety and Availability has a new charter
as of October 2006, which broadens the Committee’s scope
to include blood, blood products, tissues, and organs. It
will focus on issues related to transfusion and transplantation
safety and availability. Federal agency representation and
the committee composition also will change to encompass expertise
in both tissue and organs as well. The committee will be renamed
to reflect that change. It is hoped that these changes may
help to address cross-agency concerns.
Discussion
Dr. Yilang
Zhu asked what triggers an FDA inspection? Dr. St. Martin
responded that some are done routinely while others are triggered
by an adverse reaction report or through other channels. The
FDA may learn there are non-compliance issues, or something
that needs to be clarified. Dr. Zhu commented that Dr. St.
Martin had said there are 2,000 agencies, but the FDA only
had 153 inspections over 6 months. This amounts to one inspection
every seven years, is that right? The answer was that there
is a staffing issue at the FDA; it is ramping up capacity
for the new regulations. The Task Force mentions consideration
of prioritizing inspections, so those with higher risks are
inspected more often.
Dr. Ruth
Solomon from the FDA clarified how the estimate of “over
2,000” establishments that have been registered was
arrived at. It includes not only those that recover and process,
but also distributors -- of which there are many. The number
includes testing labs that conduct donor screening, and microbiology
labs that conduct screening and testing. It seems like an
inflated number, but it includes any entity that performs
any step in the manufacturing of tissues. The FDA cannot inspect
them all, so it prioritizes. For example, a processor would
be inspected more often than a small lab would be. The FDA
prioritizes every year and instructs the field offices about
the places on which to focus.
Dr. Solomon asked the speakers to talk about regulations around
informed consent, and specifically about international donor
sources. What’s known about the source of those donors?
The answer was that the tissue rules do not address informed
consent, just donor screening and eligibility. Dr. Solomon
said there was an AATB note about documenting consent and
understanding the source of the tissues. Is that not about
the need to attend to the source of tissues and informed consent
for them? The FDA response was that it is interested in donor
protections but authorized to protect the public from communicable
diseases. Tissue organizations have to meet FDA regulations
and there are a host of other organizations that have standards
as well.
Mr. Rigney
said that the AATB has been in top World Health Organization
(WHO) conferences to discuss specifications for consent around
tissues. AATB standards note that if a bank gets tissues from
another country, even if these tissues are just being processed
and then returned to that original country, the banks have
to be sure that they follow AATB standards as well as those
of the member states (like the European Union). There is a
global movement to improve tissue safety and to develop regulations.
The consent issue is different in different countries. A country
without its own regulations has to follow WHO guidance. This
is inserted into AATB standards.
Dr. Russell
Wiesner asked if the FDA inspections pertain to sperm and
egg banks as well. He was told they do.
Dr. Wiesner
asked if any products are coming into the U.S. from executed
prisoners from China? The answer was that this is not known,
but they would have to meet lab standards. Dr. St. Martin
is not aware that this is happening, but it would have to
be regulated. Dr. Wiesner pointed out that this does not affect
where the tissue comes from; FDA standards can be met and
still come from an executed prisoner. Those are not excluded.
Dr. Burdick clarified that the National Marrow Donor Program
is in the process of creating an arrangement with China for
the exchange of blood stem cells for transplantation with
all of the criteria that you have been hearing about. It’s
the beginning of a process for international aspects of this.
Mr. Holtzman
asked if the FDA was confident that it is aware of all of
those who are recovering tissues for transplantation. Dr.
St. Martin said that these entities are required to register
and the FDA believes that there is better diligence about
this and that things have improved. Mr. Holtzman asked if
that was a “yes”; and Dr. St. Martin said that
it was.
Mr. Holtzman
asked if medical examiners who recover dura mater/eye tissue
are subject to FDA inspection. Dr. St. Martin said that the
regulations are specific. If they have an agreement or contract
with an establishment, then the parent company registers and
makes sure its contractors comply. There are also requirements
for individuals. All entities are included in the regulations.
Mr. Holtzman asked if individuals recovering any tissue for
any reason are subject to FDA inspection. The answer was that
these individuals are required to register and subject to
inspection.
Dr. Zhu
asked what the major international sources of cell tissues
are, and Dr. St. Martin said she could look this up and get
back to him. Dr. Ruth Solomon noted that the FDA has import
regulations on any product that comes into the country. They
have to be passed by the FDA, and they cannot come into the
U.S. until there has been a review. In terms of prisoners,
any potential donor who has been incarcerated for more than
3 consecutive days may not be a donor in the U.S. So, executed
prisoners are not eligible.
Ms. Agrawal
asked why the FDA did not require AATB accreditation as part
of the new regulatory oversight. The response was that the
statutes under which the FDA operates (PHS Act) do not give
them the authority to require accreditation by any private
organizations.
Quality
of Life: Organ Donors and Recipients – Dr. Hong
Dr. Barry
Hong from the Washington University School of Medicine presented
on quality of life (QOL) of organ donors and recipients. If
one looks at the first (identical twin) transplant, in 1952,
the donor is still alive today and has stated he would make
the donation again. He responded in the way that donors do
today. A book on this transplant, by Joseph Murray, included
entries from the clinical record. From the recipient’s
psychiatric background, it seems like his QOL was shaky on
the front-end. He might have had a psychotic reaction –
it’s important to remember there were different criteria
for assessing people back then. He was restless, and tried
to cancel the operation the night before (his brother refused).
Dr. Hong noted that with that behavior, in 2007, no one would
operate on him.
“Quality
of life” was first used in cancer studies – it
is really about functional adjustments. Later, it was broadened
to include mental health and satisfaction issues.
The Karnofsky scale (Karnofsky & Burchenal, 1949) was
one of the first QOL measures. It is mainly about functionality
and if the person is functioning as he or she was before.
- 100%
- normal, no complaints, no signs of disease;
- 90%
- capable of normal activity, few symptoms;
- 60%
- requiring some help, can take care of self;
- 20%
- very ill, requiring supportive measures or treatment;
- 10%
- moribund, rapidly progressive fatal disease processes;
and
- 0%
- dead.
What is
“quality of life”? It is one of those things that
everyone thinks they know, but the specific definitions vary.
It is a very abstract idea, and a lot of domains are covered
by it, including medical, psychological, and personal domains.
It is extremely subjective, and hard to measure. There is
the notion that QOL is more than just the burden of illness
(i.e., it also includes the person’s perceptions and
meanings assigned to the experience). These domains are almost
as important as functional or symptom outcome.
The term
started in sociology, after World War II, and concerned material
affluence and things like the home and one’s possessions.
It came to medicine later and primarily in three “flavors”:
disease-specific measures, health-related QOL, and global
life quality. There is an effort to measure health more broadly.
Multi-dimensional measures (like OARS) were created, and now
we traditionally talk about dimensions that end up in a single
score (the SF-36, for example).
In 2007,
there are agreed-upon categories for the various domains,
although they may be measured differently: the recipient’s
physical functional status; his/her mental health and cognitive
status; and social functioning, meaning whether the recipient
is working, if his/her social life is active again; and global
QOL.
There
has been a change in how models or measures are seen -- biomedical
models were more linear. Now, researchers see QOL as being
more interactive; the domains feed into each other, and include
non-medical factors, rather than being linearly driven. (Wilson
& Cleary, 1995.)
More complex
modes include the work of the PROMIS Domain Framework, which
stands for the “Patient-Reported Outcomes Measurement
Information System” and which has tried to collect a
databank of agreed-upon and validated QOL measures. Dr. Hong
showed a slide illustrating the very complicated system. He
pointed out that the third column contains the usual things
about functioning, but that there are many subgroups enumerated
in addition to those. Uses of QOL indicators include assessing
general populations and for planning individual care. It is
often used by health economists to plead for more resources
for a community or region.
Dew has
noted that there are 218 studies involving over 14,000 patients,
so there is a fair amount of information available on this
subject. Studies (see Dew et al, 1997) report that improvements
in transplanted patients’ QOL are better than in other
disease groups. Outcome differs by organ groups, however (e.g.,
renal vs. heart); and it may be that these patients’
primary illness or long-term complications are very different.
It’s also noted that one does not see uniform improvement
in all four domains – some will go up and some will
not. Thus, the improvements seen may not be due to individuals,
but could result from treatment effects (such as the use of
different immunosuppressant -- cyclosporine vs. FK506).
Methodological
problems with QOL indicators are that they are subjective;
objective; and have not always separated psychopathology and
well-being. Measurements vary in terms of scales, domains,
and global measures, and the relationship among these measures
is an issue. It is hard to explain how they are connected
and interact. The search for valid and reliable measures continues.
One issue
is about QOL stability. A 1995 study conducted 5-year follow-ups
with transplant recipients found that, after about 5 years,
they stayed stable. The study controlled for age and rejection.
QOL was not influenced by age, rejection episodes, or pre-operative
medical parameters. Generally, one’s perceptions about
oneself stabilize over time.
A Spanish
study tried to answer this interesting question through a
large, randomized survey. The sample was of 210 transplants,
170 hemodialysis patients, and 402 people from the general
population (random). Instruments used included Karnofsky,
SF-36, and the SIP (Sick Impact Profile). Results indicated
that transplant patients were similar to the general population.
Co-morbid illness was similar in transplant patients and the
general population, while hemodialysis patients had more co-morbid
illness. (Rebollo, et al, 2000.)
The field
has moved into other areas, including subjective ones. Researchers
are now trying to look at beliefs, experiences, expectations,
and perceptions of illness – all of which affect QOL.
The gap between expectation and experience is important; patients
have to understand that they are not getting a new organ.
Often, patients have mistaken notions about how healthy they
will be after the transplant and get annoyed when these expectations
are not met. We may create expectations about what a person
will feel like after the donation. It is also vexing that
changes in health (biological) may not be reflected in QOL
assessments. A person’s perception of QOL is dynamic
within the individual, and equal clinical conditions do not
yield the same QOL measures. There is no clear association
between physical changes and QOL. (Burra, et al, 2007.)
Dr. Hong
has conducted a study about perceptions that looked retrospectively
at donors, recipients, and a third party who is connected
to the donor (e.g., a spouse). There were 174 donor triads
and an assessment was conducted pre- and post-transplant about
their perceptions and concerns and how they differed. Dr.
Hong showed a slide with columns indicating the respondent’s
endorsement for specific items and noted that the third party
and the donors are clearly aligned in their concerns. The
recipients have very different concerns, though they are less
concerned about death or the painfulness of surgery. There
are marked differences in measures. (Burroughs, Waterman &
Hong, 2003.)
There
will be a specific presentation later on the NIH study, RELIVE,
and QOL; but Dr. Hong noted that RELIVE has a dedicated QOL
committee. It’s like the United Nations. There are people
from all sorts of disciplines working on this. It is the biggest
effort by the Federal Government to study this. There are
specific QOL measures for each organ and measures that are
common among groups. We measure traditional domains (function,
mental, social, global) as well as some limited subjective
appraisals. We also include some newer QOL measures, i.e.,
sense of community, positive psychology. An attempt is made
to address concerns raised by the literature.
The methodology
for RELIVE is to avoid asking medical status questions that
have been asked elsewhere, and to avoid asking duplicate questions.
This reduces the response burden (shortlist instrument) but
keeps the use of validated measures intact. Questions that
emphasize subjective recall also are avoided. The instrument
can be given through in-person interview, over the phone or
paper/pencil format.
The limitations
are that the kidney and lung groups may not be comparable,
but the researchers will combine findings, if that’s
possible. Not every QOL is given, so this is not comprehensive
for some measures. The mental health measures are not equivalent
to criterion symptom-based diagnoses.
It is
a matter of discussion if they can find appropriate controls/comparisons.
No illness control group is possible. Another possible problem
with controls is the fact that controls for kidney and lung
differ. Dr. Hong stated that he likes the concept of “yoked
control.” Friends are not good controls for many things,
but they might work for living donors. Problems with using
friends as controls include the fact that people often choose
someone slightly better than themselves; it may be difficult
to motivate them for participation in the study; they have
only been used this way in a small number of studies; they
may be better at measuring objective events from donation
time until the present; and the meaning of donation may have
an unintended effect on them.
Dr. Hong
closed by talking about three psychological theories that
might throw all of our findings into concern. First, cognitive
dissonance (Festinger); second, positive and health illusions
(Taylor); and third, positive psychology (Seligman).
- Cognitive
Dissonance. People seek consistency in their beliefs and
actions. We all try to reconcile our behavior and actions
so they appear to be consistent. A person tends to reduce
the importance of something if there is a discrepancy present,
to acquire a new belief, or to remove the conflicting belief
or action. When one looks at results, they could be tilted
toward positive reactions. Examples of dissonance in organ
donation include: reducing the importance of the donation
(“It’s no big thing, it’s for my brother”);
acquiring a new belief (“It’s my opportunity
to make a difference”); removing a conflict (“I
had a bad post-op experience, but compared to my brother’s
life, my problem is nothing”).
- Positive
and Health Illusions. This theory states that illusions
are false perceptions or understandings; delusions are fixed
and false beliefs. Well-adjusted people are somewhat distorted
in their view of the world; they tend to gloss over troubles.
We have positive illusions that include the idea that illness
can be overcome or that stress leads to better emotional
functioning. The mind imposes meaning on challenging events.
But, it turns out that optimistic cancer patients have better
outcomes. Thus, sometimes these delusions can be helpful
in fostering health. Depressed patients are much keener
observers of the world than non-depressed people.
- Positive
Psychology. This states that positive and happy people engage
in actions that suggest life is positive, and seek meaning
in positive activities – just like organ donors do.
Zest, gratitude, hope, and love are associated with life
satisfaction (in contrast to the value placed on cerebral
strengths such as curiosity and love of learning). Positivity
is associated with life satisfaction. These people tend
to do better than those who have high levels of being curious
or of loving to learn (e.g., scientists).
Discussion
Ms. Agrawal
thanked Dr. Hong for an interesting presentation.
Mrs. Rhonda
Boone said that she was excited to see this subject on the
agenda and asked where Dr. Hong had gotten the information
presented. She noted that quality of life is something that
is often ignored in living donors and asked if this was this
from published studies about recipients. Dr. Hong replied
that the published studies (e.g., Dew) are mostly about organ
recipients. There is a misconception that nothing has been
done in this area, but this is not the case. In fact, much
work has been done -- but no one knows what it means. The
literature is confusing and conflicting. Mrs. Boone asked
if the study he is conducting includes any items to determine
the high number of complications that affect donors and recipients.
The response was that the researchers are very much aware
of the limitations; there are lots of analytic models to use.
We can look at complications and see if the variables predict
QOL. It’s hard, though, to see how they influence one
another. It will give us better answers, but they may not
be perfect.
Dr. Mildred
Solomon said that this was a very interesting presentation.
She is puzzled, however, that one would have to defend the
subjective nature of QOL assessments. She mentioned pain measurements
and commented that researchers in that field have embraced
the subjectivity of those measurements. Dr. Hong responded
that it depends on “who you hang out with.” Measurement
folks hammer him on this all the time, while QOL people often
say it’s all subjective. Folks line up all over the
place. There is a lot of debate about this and if you use
validated measures, then what are the constructs? Dr. Solomon
asked if he was saying that there is a difference in QOL assessment
between people in pain and organ donation. Dr. Hong answered
that it’s tipped to a positive direction; you can’t
get away from that.
Ms. Principe
asked about cultural issues. Dr. Hong said that when there
is a family member who is a potential donor, with White families,
there are few people in the room and one person (like the
father) makes the final decision. With African American families,
however, the waiting rooms tend to be too small; the families
have 50-60 people present. It can be hard to make a decision
that way and, if one person doesn’t want to do the donation,
other family members will not override that person. Such cultural
issues may feed into lower approval rates for organ donations
among certain minorities. There may also be QOL variations
by cultural groups. If it emphasizes something different,
it will impact the QOL assessment. He referred Ms. Principe
to “PROMIS,” which has a lot of details. Since
Ms. Principe is from New York, she stated she is thinking
in terms of the live donors and the QOL for them based on
cultural diversity issues. There is a lack of data on this.
Dr. Hong agreed that this is very complex and that he hopes
to get to it at some point. He wants common measures right
now. The goal is to define QOL better so it can be used as
a measure across the various groups.
Dr. Jorge
Reyes said that, as a clinician, they deal with outcomes to
affect initiatives. Where might this be going in terms of
impact and the field? And, is there another area of medicine
where QOL has impacted practice? The answer was that cancer
seems to be doing better – the cancer field can say
if a treatment is better or worse in terms of QOL domains
(e.g., getting the person back to work). It’s complicated.
Memories are distorted in every aspect of life.
Dr. David
Vega asked if Dr. Hong thinks QOL measures are sophisticated
enough to impact allocation decisions among deceased donors.
The short answer is no. For some patients, some things will
be better. We have a terrible dilemma of trying to have global
goods and an individual patient with a specific disease and
a prior quality of life.
Dr. Zhu
asked about promoting positive psychology as a way to promote
donation. Dr. Hong responded that he is very interested in
living, altruistic donors. They are very different, and special;
it’s about their personality and not about education.
They may have a gene for altruism and be wired differently.
Our research is showing there seems to be a different type
of person, different from relatives and from the general public.
The MMPI has a scale (the S scale) that is based on airline
pilots – they tend to be sociable, self-directed, to
work well with others, and to make their own decisions. Altruistic
organ donors look the same. They have strong views, are firm,
and are socially proactive.
National
Institutes of Health (NIH) Studies of Living Donors –
Dr. Odim
Dr. Jonah
Odim began by noting that 15 years ago his stepsister, who
was newly married and had just relocated to Texas from West
Africa, was in kidney failure from unknown causes. She approached
her twin brother (who was living in Chicago) about donating
one of his kidneys. Although they were fraternal twins, the
two had not grown up together and had been separated during
the Biafran Civil War in the late 1960s. Despite pleas from
the family, the brother ultimately decided against undergoing
a donor medical and psychosocial evaluation. The stepsister
went on to dialysis and eventually received a renal transplantation
from a deceased donor, but is now back on dialysis.
This scenario
shows the rollercoaster, emotional ride surrounding living
donor transplantation. Dr. Odim stated that he will briefly
review NIH’s research initiatives to look at outcomes
among living organ donors. Specifically, he will describe
the five protocols that are currently in various stages of
development and some of the factors that affect the time and
pipeline of new information regarding research of this nature.
We all
know that there is a chronic shortage of organs, and that
there are deaths among those who are on the waiting lists.
The push to meet the demand has fueled debates in the lay
press. For example, this week the Wall Street Journal
published an article on sales of organs. Issues related to
live organ donation also recently have been discussed in the
New England Journal of Medicine.
What do
living donors need to know? The Wall Street Journal
has published articles noting the need for long-term outcome
studies in living donors of solid organs. It is important
to recognize that live organ donation is a relatively young
science. There is a mere 13-year history for lung donation,
20-year history for liver transplants, and a little more than
50-year history for kidney donation. So, no one knows precisely
what the time-dependent, natural history is for a particular
individual live donor.
The rising
number of donors suggests that there are benefits to becoming
a donor – for the donor, the recipient, and the health
care field. The potential benefits for the living donor include
respect for autonomy, a psychological benefit from the altruistic
act, and (in other parts of the world) financial benefits.
The recipient usually benefits from reduction in the time
they have to wait, reduced chance of dying on the waiting
list, reduced down time “in the ice bucket” that
reduces organ ischemia, and improved graft and recipient survival
(in most instances).
Looking
at outcomes for living donation, it’s clear that, for
kidney at least, mortality rates associated with living kidney
donation are very low. No early mortality has been reported
for lung transplantation cases. Morbidity rates for liver
donation are all over the map. Only three centers do live
liver donations and their mortality ranges from 20-50 percent.
Early mortality after living kidney donation is about three
deaths in 10,000 (this is similar to the risk from general
anesthesia), with morbidities reported around 1-10 per 100
cases.
Living
lung and liver transplantation are technically and physiological
more stressful procedures. About two in 1,000 donors of a
liver segment die early in the short-term. Short-term morbidity
is appreciable in 10 out of 100 of the cases. Donor lobar
transplantation involves a pair of donors per recipient. There
have been no reported deaths in the short (13 years) experience
at the few U.S. centers that offer this service. On the other
hand, minor and major complications are seen.
The ACOT
recommended, and the Secretary agreed, that NIH should support
a research program on the outcomes for, and health care needs
of, living donors. The NIH responded by funding two consortia
of investigators. The “Adult to Adult Living Liver”
(A2ALL) donor study, supported by NIDDK, was initiated in
2002 with funding for seven years. It is a consortium of nine
U.S. clinical liver transplantation sites.
The second,
and more recent, is the “RELIVE” study, which
stands for REnal and Lung LIVing donors Evaluation study.
This got underway last fall with three kidney and two lung
sites. The three clinical kidney sites are the University
of Minnesota, the Mayo Clinic, and the University of Alabama.
Together, they provide long-standing expertise and regional
and ethnic diversity. The two lung sites are U.S.C. and Washington
University (in Ohio) that, together, have performed over 80
percent of all the living lung transplants in the U.S. since
the technique was initiated 13 years ago. The consortium of
investigators is funded by predominantly by NIAID with supplemental
support from NHLBI and HRSA. The data coordinating center
for RELIVE also coordinates the A2ALL group.
If one
looks at the race distribution of living donors and living
donors on the waiting list, among donors who need a kidney
graft, almost half are African American. Risks may be variable
based on a number of predictors: socioeconomic status, ethnicity.
This raises issues for the field. (Gibney, 2007.) Looking
at donors, there were over 62,000 living donations made between
1993 and 2005. While only 14 percent of this group was African
Americans, African Americans represented almost 50 percent
of living donors going on the ESRD and wait listed for a new
kidney. What is the age-gender and race-adjusted risk of ESRD
after living kidney donation?
The RELIVE
study is doing a chart review to explore the status of all
live kidney donors in their catchment area. Information about
donors will be linked with a variety of databases the researchers
will identify. Comparisons will be made with control groups.
The next phase on kidneys is a cross-sectional protocol with
the primary endpoints being: (1) Hypertension, proteinuria,
renal disease, and anemia; (2) Risk for cardiovascular disease;
and (3) Quality of life and insurance risk. Secondary endpoints
include differences in primary endpoints (race, surgical technique,
ECD vs. SD, time from donation, donor family history); and
accuracy of GFR vs. measured GFR.
For live
liver donation a similar strategy is being used. A retrospective
analysis will be conducted to determine the status of all
of the patients, looking at endpoints about death as well
as other milestones (e.g., cause of death). Also, we will
assess if any of them are on the lung transplant lists. Dr.
Odim described the methodology for the RELIVE studies.
The few
studies conducted on informed consent are all retrospective
and are subject to limitations that include “recall
bias.” There are no prospective studies of the donor’s
understanding of the process at the time of their donation.
“Informed consent” is the act of an individual
exercising an autonomous choice about whether to undergo a
living donation. Non-control (or “voluntariness”)
is fundamental to autonomous actions. Control can be exerted
through influences that undermine the voluntary (or non-controlled)
nature of the actions. These influences include persuasion,
manipulation, and coercion.
The informed
consent portion of the study will be a short-term prospective
survey for kidney and lung donors. Primary endpoints include
their understanding of pressure to donate; the process of
donation; medical and psychosocial consequences of donation;
and center and ethnic/racial variability. Secondary endpoints
include the understanding of short- and long-term medical
risks; psychological risks; and variable recipient outcomes.
QOL focus
will have the goal of assessing the long-term quality of life
in living kidney and lung donors compared with matched control
subjects, and identifying predictors/correlates of long-term
quality of life following living kidney and lung donation.
Dr. Hong’s presentation covered this issue.
The data
coordinating center is taking the data sets from the individual
centers and trying to make linkages with a variety of databases
to fill in gaps and create a complete data set. The ultimate
database will be similar to the A2ALL one.
We do
have some preliminary data from a dry run that looks at kidney
donors by site and the year of donation. We have data from
70 percent of these donors (for lungs, we have about 80 percent
of cases). Data do not include cases from before 1980s, when
SRTR was launched. In terms of deaths per year among the kidney
group, there is only one that was reported to the SRTR; but
when linkages were made with other databases (e.g., Social
Security), more instances are found. The cause of death is
unknown, however. It is the same with lungs -- there is one
from the SRTR data.
Study
wide design issues include: HRQoL (validated tools, disease-specific
tools); selection of controls (disease-free; comparable time
at risk; age, race and gender-matched); and ascertainment
of donor outcomes (standardized definition, uniform ascertainment
method; practical, adjudication mechanism).
A JAMA
article on the impact of HIPAA on health care research is
interesting and notes that when the researchers looked at
the impact of the rule (which went into effect in 1993), they
determined that it has made it significantly more difficult
to do research. The consensus also was that HIPAA has not
strengthened the public’s trust in the process.
In conclusion,
living organ donation is perhaps one of the remarkable success
stories of modern medicine. We have witnessed the heroism
and compassion of well-motivated individuals who take risks
to help others. The generation of new knowledge (especially
patient-oriented research) involving multiple investigators
and researchers, and encompassing the impact of IRB and HIPAA
requirements, impairs the speed at which the information is
generated.
The NIH
wishes to thank HRSA and other agencies for sharing with NIH
in trying to get this research underway.
Discussion
Mrs. Boone
asked if there are safeguards in place for this and/or for
the liver study to ensure that the transplant center information
is complete and accurate. Dr. Odim asked if she meant, are
there safeguards that it’s safe and accurate, then to
the extent possible, yes. It’s retrospective information,
however, and it will depend on what the safeguards were in
place when the donor was in the specific facility. Mrs. Boone
asked if the information from Social Security and the centers
can be compared to determine why the patients died and to
see the discrepancy. Dr. Odim said most definitely this can
occur. But, not everyone has a Social Security number, so
even this is not a failsafe method. NIH is going to do other
things to help the group get that information.
Dr. Low
commented that the mortality figures presented seemed low.
Do they cover the whole time period, because they seem lower
even than would be seen among the general population? If the
rates are that low, he joked that he wanted to get a transplant.
Dr. Odim said the rates do cover the whole time period of
20 years. He stated that Dr. Low’s points are excellent
and cautioned that these are preliminary data. There are plans
to look at this more closely.
Dr. Velma
Scantlebury thanked Dr. Odim for the presentation. She asked
for clarification about the statement that there were 13 deaths,
but only one was in the SRTR? Dr. Odim stated that this was
correct for kidney donor deaths; that is the number or reported
deaths for that institution among donors. Dr. Burdick commented
that SRTR data are collected by OPTN, which does not collect
long-term data. Because these are deaths that come from any
cause, they have no way to track them. There’s no discrepancy;
it’s just what SRTR collects. The OPTN didn’t
exist before 1987 so that would have been voluntary reporting
before then. Dr. Odim agreed and said that RELIVE wanted to
look and see who is alive, and then they can be contacted
for follow-up.
Dr. Wiesner
reminded the group that the processes have evolved too. We
now take hypertensive or older people; the donors over time
are not comparable. Dr. Odim agreed that it’s a moving
target; we are taking more donors who are obese, old, medicated
and that was not the case 10 years ago. The role of the consortium
is to see if all 8,000 living donors are alive or dead, and
to collect circumstances of death for all who are not alive.
Reports
from Workgroups: Discussion & Recommendations
Ms. Agrawal
announced that the ACOT would hear reports from workgroups
and get their recommendations. The workgroups will present
in the order listed on the agenda.
Tommy
Frieson -- Transplant Tourism Workgroup
Mr. Frieson
began by noting that the demand for donations in the U.S.
exceeds supply. As a result of that and the length of the
waiting list, people are seeking organs outside of the United
States. Countries such as India, Thailand, China, and South
America (to name just a few) are getting involved in “transplant
tourism.” Issues include: where the transplanted organs
come from; the quality of care received by the recipient;
the recipient’s ability to get follow-up after the donation;
levels of care for live organ donors; the recipient’s
lack of ability to litigate, if needed; and possible threats
to insurance coverage for the transplant and/or for any needed
follow-up?
Dr. Frank
Delmonico spoke to the ACOT about this issue in May 2007.
His talk described how the poor and vulnerable are being victimized.
They are frequently paid very small amounts for organs and
not being properly taken care of afterwards. Also, there are
questions about U.S. surgeons who go to these countries to
perform transplant operations.
Two articles
are provided in the ACOT member packets relevant to this topic.
Mr. Frieson tried to contact insurance companies. He contacted
United Health Group Programs, U.S. Health, and Blue Cross
Blue Shield (BCBS) of South Carolina. The first two did not
return his call. BCBS did and he learned that BCBS transplant
patients are leaving the country because of monetary issues.
Mr. Frieson was assured that the international facilities
were monitored. The BCBS representative said that this was
happening because people were not able to wait or to pay for
organs. In fact, BCBS saves a lot of money because of this
sort of “medical travel.” When a person goes to
Thailand, he/she brings his own living donor. BCBS then takes
care of them as a patient. The conversation did not address
issues of prisoners’ organs.
Mr. Frieson
asked why someone would have to wait for a transplant in the
U.S. if this individual was on the waiting list and had an
identified living donor. The BCBS representative did not answer
this point. Ms. Agrawal noted that the costs would be primarily
either BCBS’ own or Medicare’s, not the patient’s.
Mr. Frieson said he had mentioned that and the BSBC representative
responded, “This is what we do.” Then, no future
calls from Mr. Frieson were answered by BSBC. The workgroup
has discussed this issue and also talked to Dr. Delmonico
about Chinese prisoners being killed for their organs.
Proposed
Recommendation: Transplant Tourism Workgroup
For
waitlisted patients removed from the waiting list because
of transplant, the ACOT recommends that the OPTN create
a unique code for transplants that occur outside the U.S.
That code will lead to the collection of follow-up information
on those patients, e.g., where the transplant occurred,
type of transplant, basic post-transplant health condition
information. The patient would be followed at the hospital(s)
where post-transplant treatment is provided in the same
manner as other transplant recipients.
For
non-waitlisted patients who receive a transplant outside
the U.S., the ACOT recommends that the OPTN seek the cooperation
of transplant programs in identifying those non-U.S. transplant
patients they are treating, and then in collecting the same
type of information as for those patients who had been waitlisted.
Discussion
Dr. Alan
Leichtman from SRTR noted that the OPTN has been collecting
some of this information although they have not conducted
an audit on this. A more systematic tracking of this is beginning.
It’s important to recognize that some of these foreign
operations result from transplant tourism, but others are
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