Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

1. Does mass spectrometric analysis and therapeutic monitoring of tacrolimus as compared with immunoassay analysis and therapeutic monitoring produce a) better organ survival rate, b) fewer rejections, c) less nephrotoxicity and/or d) cost savings in renal transplants?
2. Does two hour post peak cyclosporine monitoring produce a) better organ survival rate, b) fewer rejections, c) less nephrotoxicity, and/or d) cost savings in renal transplants than trough monitoring?
3. Have multidrug protocols to target lower tacrolimus levels been effective at producing a) better organ survival rate, b) fewer rejection episodes, c) less nephrotoxicity,and/or d) cost savings in renal transplants?

• Have acute rejection rates decreased with the addition of thymoglobulin to a tacrolimus low target level anti rejection regimen in renal transplants?

4. Are analytical capabilities sufficient to measure tacrolimus in the lower ranges that multidrug protocols to target lower tacrolimus levels would require?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

low target level tacrolimus regimen with and without thymoglobulin as compared with traditional immunosuppression regimen, 2 hr post cyclosporine monitoring compared with trough monitoring, analytical methods to monitor a low target tacrolimus regimen

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

adult renal patients

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

no

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

a) better organ survival rate, b) fewer rejections, c) less nephrotoxicity and/or d) cost savings in renal transplants?

Describe any health-related risks, side effects, or harms that you are concerned about.

no

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

None

AHRQ Priority Populations

None

Federal Health Care Program

None

Importance

Describe why this topic is important.

The disease burden is complications and/or failure of immunosuppressant therapy in transplanted patients. While one year allograft survival has improved dramatically, 5 and 10 year graft survival rates for both cadaveric and living related donor renal transplant recipients are still low ( 5 year cadaveric 65%, 5 year living related 78% 10 year cadaveric 37% and 10 year living related 54%). In addition, 31% of deaths in renal transplant patients were deaths with a functioning graft from

co morbidity causes in the time period 1987-2001.

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

This is a joint submission of the American Association of Clinical Chemistry and National Academy of Clinical Chemistry Evidence Based Medicine subcommittee. We have conducted a full day symposium at our national meeting with international speakers on this topic.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

linkage of 1)outcome to low target tacrolimus regimen,2)addition of thymoglobulin to low target tacrolimus regimen, 3) 2 hr post dose cyclosporine,

and 4)analytical methods used to monitor drug levels

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

The AACC and NACB have collaborated in other AHRQ activities and have done so actively and with commitment and follow through.

Describe the timeframe in which an answer to your question is needed.

1 year to 18 months

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

none

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

The AACC and NACB have collaborated in other AHRQ activities and have done so actively and with commitment and follow through.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program

AACC and NACB have worked with AHRQ before