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

For hemophilia patients, would the use of Fresh Frozen Plasma or cryoprecipate in the initial stages or treatment for previously untreated patients (PUPS) reduce the risk of inhibitory antibody production.

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:

Fresh Frozen Plasma and cryoprecipate versus specifically licensed clotting factor replacement agents, to reduce the risk of inhibitor anitibody development in previously untreated patients.

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.)

Patients who have not as yet been treated with clotting factor agents. This would most likely be patients under two years of age. Most hemophilia patients are first exposed to clotting factor therapy either in response to a bleeding episode or due to trauma or surgery. Studies have shown that up to 30% of these patients will develop inhibitory antibodies to treatment which can significantly alter the course and treatment options for the disease.

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

Since severe patients (those with natural factor VIII or IX levels <1%) are at the highest risk for developing inhibitory antibodies. Also, patients with specific gene mutations, certain ethic backgrounds, family history or inhibitory developement, or those being treated for a surgery or major bleeding episode are at the most risk and should therefore receive priority consideration in being studied.

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

Avoidance of or reduction in rate of the development of inhibitory antibodies in previously untreated patients. If inhibitors can be avoided or reduced, these patients will benefit from the currently available clotting factor replacement therapies and may avoid many of the significant complications associated with being unable to use the current products to control and prevent bleeding.

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

Viral contamination of FFP and cryoprecipate, while generally thought to be low is still considered possible. Less effective control of serious bleeding episodes.

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)

• Arthritis and nontraumatic joint disorders
• Functional limitations and disability
• Infectious diseases, including HIV/AIDS

AHRQ Priority Populations

• Children
• Individuals with special health care needs, including individuals with disabilities or who need chronic care or end-of-life health care

Federal Health Care Program

• Medicaid
• Medicare
• State Children's Health Insurance Program (SCHIP)

Importance

Describe why this topic is important.

I am the parent of child who has severe hemophilia A and developed an inhibitor antibody to clotting factor replacement therapy at six months of age. Due to to presence of the inhibitor, his bleeding has never been effectively controlled and has not been able to be prevented. He has suffered hundreds of bleeding episodes, which have destroyed his joints and left him wheelchair bound. He has endured numerous hospitalizations and other medical complications. The cost of his treatment has been enourmouse. To date his medical bills have exceeded over $35 million dollars. His monthly medical expenses average over $500,000 (which is mostly attributed to the cost of alternative clotting factor medications (called bypassing agents) which are utilized to try to control or prevent bleeding without much sucess.

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.)

I am involved with hemophilia groups across the nation and am seeing this same situation continue to affect many newly diagnosed patients. It seems like no progress has been made towards resolving this problem in over 20 years. I would like to see future generations of people with hemophilia spared this outcome. My father, who also had hemophilia and was originally treated with whole blood, fresh frozen plasma, and cryoprecipate, never developed this complication (although he did contract HIV and succumb to AIDS in the early 1980's). I have been around the hemophiia community all of my life and have noticed a much higher rate of inhibitor developement and the devasting consequences this causes. I have looked into what research is currently being done in the United States on this subject and am disappointed with the small number amount of researh being done and the slowness of any progress towards resolving this critical complication or factor replacement therapy.

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:

Yes, regression to the use of FFP or cryoprecipate would most likely be viewed by clinicians and hemophilia organizations as reverting to a less effective treatment method. However, with the rate of inhibitor development possibly increasing and affecting such a large percentage of patients, and no specific progress being made towards developing less immunogenic therapies, it seems like investigation of how to use known treatment methods (possible even older treatment methods) to curtail the development of inhibitory antibodies in high risk populations, should be considered.

Potential Impact

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

If an alternative treatment protocol in the early stages of a hemophilia patients treatment could reduce or eliminate the chances of inhibior development, treatment recommendstions could be adapted to implement these protocols and spare hundreds or thousands of patients from developing inhibitory antibodies, which would significantly improve their response to treatment, reduce their cost of care and improve their quality of life.

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

Urgently, as soon as possible. Everyday more hemophilia patients are born and begin treatment with clotting factors. Once an inhibitor develops in a previously untreated patient, the entire course of treatment changes and the risk for complications and adverse events (including death and disability increase). The costs of care increase significantly once this happens. There are now over thousands of hemophilia patients with inhibitors in the United States, this number will increase everyday until an answer can be found.

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

Due to the high cost of care many patients who develop an inhibitor face, health insurance and health care options are limited. Studies have shown that over 50% of patients are forced to rely on Medicaid, SCHIP Programs of less optimal means of care.

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)

If an alternative treatment protocol in the early stages of a hemophilia patients treatment could reduce or eliminate the chances of inhibior development, treatment recommendstions could be adapted to implement these protocols and spare hundreds or thousands of patients from developing inhibitory antibodies, which would significantly improve their response to treatment, reduce their cost of care and improve their quality of life.

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

Individual

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

Internet