IS FOCUSING ON "PATIENT SURVIVAL" REALLY IN OUR PATIENTS' BEST INTERESTS?

Healthcare stakeholders are "buzzing" about the QUALITY of healthcare - rightfully so. As in other arenas, excellence is easily recognized and can be magnificent but is difficult to achieve. A central issue in the ongoing discussion is how to measure and describe points along the Quality spectrum with sufficient accuracy for patients, payers and providers themselves to make decisions based on the results.  How do we deliver care? When do we deliver care (is it timely?)? Are  the outcomes of care are what they should be?  Even whether end of life care was compassionate and competent are some of the questions being asked. In the field of transplantation, even the most basic outcome measure - Patient Survival 1 Year Following Transplantation -  already in use by United Network for Organ Sharing (UNOS)  and Center for Medicare and Medicaid Services (CMS) (and virtually all healthcare payers) to determine whether or not transplant centers meet regulatory expectations, has multiple imperfections as a quality measure.

Let's examine why use of the 1 Year Patient Survival measure to assess the quality of care at a specific transplant center is so tricky. If an imaginary center called the "Chimera Center" has a 1 Year Patient Survival for liver transplants of 100%, it would appear to be doing an excellent job, right? In fact, to achieve that rate, the Chimera team may have turned down patients that were quite sick and, they feared, had too high a likelihood of not surviving the transplant. But, at least some of these patients would likely have been considered acceptable candidates at other transplant centers, and were therefore being denied access to transplantation. Similarly, the Chimera team may have been too "selective" about which organs they accepted for transplantation - again denying patients adequate access to transplantation.

The (mythical) Chimera team that appears to deliver outstanding quality liver transplantation might also be loathe to participate in clinical trials of new drugs or therapies for their patients because of potential adverse impact on their center's patient survival rates. So, unfortunately, the regulatory focus on patient survival rates tends to impede clinical research that may offer advances in transplantation.

If the Chimera Center's most recent 1 Year Patient Survival rate was significantly below the expected rate, any of the factors discussed above may have been responsible. However, it is also possible that the transplants were not well performed, the care during the first post-transplant year was sub-optimal, or there was a combination of both issues. Regardless, changes would be required within the Center's approaches. But, now the Center will have difficulty persuading payers to allow subsequent transplants to be performed at Chimera. This negative selection bias will drive away the best quality patients (however that is measured) and tend to leave the sickest patients for transplantation at Chimera. The Center will therefore be facing a major uphill battle to re-establish a good 1 Year Patient Survival Rate even if all of the appropriate changes have been implemented. Local patients will still have limited access to transplantation because of the challenges of traveling to remote centers and the issues facing Chimera.

This issue of clinical data measurement is front and center in the field of clinical transplantation. The annual American Transplant Congress is about to begin in Seattle, Washington. Stay tuned for updates on this and other topics in subsequent posts.

TISSUE ENGINEERED KIDNEYS + TRACHEA ARE NEW ON THE BLOCK

Tissue engineers strive to construct whole organs for clinical reconstruction or transplantation from components that did not naturally co-exist or may not even be natural. The world has been in a bit of a tizzy because of two different and unrelated advances that became public within two weeks in April, 2013. In the first, kidneys whose cells were removed but whose microscopic infrastructures were kept intact, were reconstituted with two types of cells (epithelial and endothelial). The kidneys (from rats) exhibited some function both in the laboratory and when transplanted (small amounts of urine in rats). In the second, a 32 month old child whose own trachea did not develop, received the world's first bioartificial trachea  engineered from an artificial nanofiber scaffold and stem cells taken from her own bone marrow. In both cases tissue engineers have accomplished incredible feats.

Just imagine the sequences that could result. Rat kidneys that function after transplantation might lead to the ability to engineer human kidneys following the same principles. Suddenly, there might be a way to help the 100,000 people currently waiting for deceased donor kidneys in the U.S. Others who dared not even dream of trying to qualify for a transplant might now do so.

Clinical success with the bioartificial trachea is even more stunning. Direct application of translational science in a living person. Since the living cellular component is her own, there is no expectation of rejection. No need for immunosuppressive medications. What a win-win situation! How many other ways can you imagine using bioengineered body components to fill in missing body parts caused by congenital defects, disease or trauma? Perhaps now the cause for excitement is clear.

We should also take particular note of the timing of these two announcements. Unlikely that serendipity is involved. Maturation of multiple skills, technologies, concepts and prior developments in a field often combine to make a ripe environment for talented researchers to work in - a sort of perfect scientific storm. These leaps forward could probably not have occurred twenty years ago. But today, the time is right. Let's hope that other exciting announcements follow.

WHY TRANSPLANT A UTERUS?

Roughly half of humanity does just fine without a uterus. The rest of us only experience function during a minor (approximately 12 -48 years of age) portion of our life cycle. While even those years of uterine function remain essential for the survival of our species (despite the amazing reproductive technologies available today), they are not for the individual's survival. For this reason, a uterus- of which there has been one publicly known successful transplant survivor to date - falls into the category of "Quality of Life" transplants. Different from the other organs in that category - the hand, face and larynx-, this is the first vascularized (with a specific reattached blood supply) organ transplant of any type that is intended to be temporary. What a mind boggling concept! It seems that the patient and transplant team expect to stop the anti-rejection medications and remove the uterus following the conclusion of child bearing. Quite logical actually. Why keep a woman on immunosuppression one moment longer than necessary?

Still, this new area raises revolutionary questions.

• Does it make sense to try to control the immune system's response with potent drugs that can cause life threatening infections and cancers just for a few years and to hope for recovery of that system through withdrawal of the medications and (presumably) the uterus? 
• Will the immune system recover back to baseline? Are experiences with failed kidney transplantation an appropriate model?
• Are there long-term consequences for the patient? 
• Who should pay for the privilege of this non-life saving transplant?
•  Are there really enough resources available to support widespread use of a therapy that is not required and may indeed be harmful? 
• If not, and it will only be available to wealthy individuals, should they be permitted to engage the nation's network of donor identification and the organ allocation system in order to find the needed uterus? 
• If not through that means, how will they find a uterus?
• Is it reasonable to intentionally expose a helpless fetus to development while receiving immunosuppressants? To the unknown impact of growth within a transplanted uterus? Who should consent for that fetus?
• Since all nerves to the uterus were cut when it was removed from the donor will the patient/recipient feel contractions (!)?

Yet another typical day in donation and transplantation. A real life situation that could not have been imagined if one had tried. Never a boring day. Trying to achieve equity. Failing to do so because of the resource shortfall. Ethical twists and turns. Learning something every single day.

Those who have never faced infertility issues may not fully understand the strength of the drive for procreation which must be the motivation for a uterine transplant. Among the amazing range of available reproductive technologies, none quite match up to this one. The closest, the use of a gestational surrogate to carry your pregnancy is still not the equivalent of carrying your  own pregnancy, to feeling life within your body, or to delivering your own child. The patient's interest in this transplant is quite understandable. Whether the investigators should perform it when more standard approaches would likely produce a baby with greater certainty is the key, new question on the table.

Thus far, the world has been notified that a first pregnancy has occurred through in vitro fertilization (IVF) and is six weeks along. This patient was also the world's first successful recipient of a uterus transplant. Since then a Swedish team has performed 2 successful mother-to-daughter uterus transplants. Despite the questions and reservations that come to mind, this incredible step in the science and medicine of transplantation now involves a real woman (her name is Derya Sert) and her fetus (with an audible heartbeat). It will be a privilege to provide subsequent comments on even more progress as they share their experiences with the world.

CITIZEN ACTION NEEDED TO HELP KIDNEY PATIENTS - AGAIN

U.S. kidney transplant patients are caught in a political/fiscal Catch-22 that leads to cessation of Medicare coverage for their anti-rejection medications at approximately $10,000 to 20,000 per year, 36 months after transplantation. A proven outcome for some patients has been failure of the transplant with a return to expensive dialysis - again paid for by Medicare, this time at an approximate cost of $70,000 per year. Ridiculous, right?

http://www.govtrack.us/congress/bills/113/hr1428#

Ironically, this dilemma fits well into the mutual history of kidney disease and Medicare. We now take Medicare coverage of dialysis for granted. But it was an individual citizen's definitive and courageous act that helped establish that new entitlement forty years ago. Shep Glazer, a 43 year old husband, father and salesman, supported by the precursor organization to today's American Association of Kidney Patients,  and other stakeholders, opted to be openly dialyzed on the floor of the Ways and Means Committee, stunning everyone on November 4, 1972.  His "excellent testimony" made the point. Chronic kidney failure was adopted into the Medicare program in October 1972.

It appears that Congress may now finally be committed to fixing this medication coverage problem.  Another step has just been taken on the legislative pathway, but a few major ones are still required (make it out of House and Senate Committees, approval by House, approval by Senate, negotiation + agreement by House + Senate members, Presidential signature). Kudos to Representative Michael Burgess from Texas who introduced the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act of 2013  
into the House of Representatives on April 9, 2013. The House Bill was referred directly to the House Ways and Means Committee on the same day and matches the Senate Bill previously introduced on February 13, 2013 by Senators Durbin and Cochran. Both would remove the medication coverage cliff awaiting patients at 36 months following kidney transplantation.

Noted clearly on the government website is the low percentage of bills that make it out of Committees for consideration by the entire House or Senate; only 13% of House bills and 1% of Senate bills succeed to the next procedural step. If our dual immunosuppressive bills don't make it out of their respective committees, they will be "dead" and the Catch-22 will continue. This is where your help is needed - really. We must help push these bills out of committee for consideration by the entire legislative bodies.

Politicians respond to their constituents, especially when significant numbers of citizens make the effort to respectfully express an opinion through the system. To date, it appears that only 35/435 Representatives have signed on as co-sponsors of the Burgess bill, and 5/100 Senators have signed on as co-sponsors of the Durbin bill. Many of our legislators need to hear directly from us about these bills.

Spend some time now confirming the identity and contact information for your own Senators and Representative.   If your politician has already "signed on" to the appropriate bill (the Senate bill for a Senator, the House bill for a Representative), call or e-mail to say; "Thank- you for signing on to the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act of 2013".  If the individual has NOT YET signed on, indicate that you believe that signing on is important - and why.

Special effort should come from constituents who live in the districts and states of the House Ways and Means and Senate Finance Committee members. They include:

You will be joining an important and proud tradition of citizen voices shaping Congressional action. Shep Glazer's personal action was considered "excellent testimony" and made a real difference. Your personal phone calls and e-mails will be too.