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Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary (2011)

Chapter: Appendix B: Comparative Effectiveness Studies Inventory Project

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Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Appendix B



Comparative Effectiveness Studies Inventory Project

A commissioned activity for the IOM
Roundtable on Evidence-Based Medicine

In 2008, a working group was formed at the request of the IOM Roundtable on Evidence-Based Medicine to identify and consider compelling comparisons of clinical interventions in order to inform and advance discussions of criteria important to determining priorities for assessment, to identify a list of possible interventions to be considered, and to offer observations on the kinds of studies needed. Material was presented in draft form at the July 2008 IOM workshop on infrastructure needs for comparative effectiveness research and delivered in final form in March 2009. An abridged version of the text follows, drawn from material produced by Douglas B. Kamerow, M.D., M.P.H., consultant and working group convener, and is based in part on meetings and conversations with working group members. This portion and the complete paper have not been reviewed and should not be considered a product of the Institute of Medicine, the roundtable, or the individual members of the working group.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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STUDY TOPIC SUMMARIES

Diagnosis and prognosis of breast cancer using genetic tests:
HER2 and others

Drug treatment of depression in primary care

Drug treatment of epilepsy in children

Gamma knife surgery for multiple types of intracranial lesions:
comparison with surgery and/or whole brain radiation

Inguinal hernia repair: open vs. minimally invasive

Outcomes of percutaneous coronary interventions in hospitals with and without onsite surgical backup

Over-the-counter drug treatment of upper respiratory tract infections in children

Prevention and treatment of pressure ulcers

Screening hospital inpatients for methicillin-resistant
Staphylococcus aureus infection

Tobacco cessation:
nicotine replacement agents, oral medications, combinations

Treatment of acute thrombotic/embolic stroke:
clot removal, reperfusion drugs

Treatment of ADHD in children:
drugs, behavioral interventions, no Rx

Treatment of chronic atrial fibrillation:
drugs, catheter ablation, surgery

Treatment of chronic low back pain

Treatment of localized prostate cancer:
watchful waiting, surgery, radiation, or cryotherapy

Use of erythropoiesis-stimulating agents in the treatment of hematologic cancers

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Diagnosis and Prognosis of Breast Cancer Using Genetic Tests:
HER2 and Others

Brief description of the condition or problem

In 2008, there were an estimated 185,000 new cases of breast cancer in the United States, and more than 40,000 women died from breast cancer. Breast cancer has long been known to be a heterogeneous disease, varying by estrogen receptor expression, tumor grade, and patient age. These characteristics affect diagnosis, prognosis, and treatment. More recently, gene expression status has been added to the list of variations. Multiple studies have proposed many ways to organize gene expression differences in breast cancer. Most genomic-based studies have reported that breast cancer constitutes at least four different entities, with differing gene expression profiles, molecular markers, prognosis, and treatment sensitivities. What are the clinical and treatment implications of these profiles and the resulting tumor markers?

Available treatments or interventions

Many treatments for breast cancer exist, such as chemotherapeutics and surgery. Some breast cancers express tumor markers that provide specific targets for treatment. For example, human epidermal growth factor receptor 2 (HER2), a protein involved in normal cell growth, is found in high levels on some breast cancer cells. This so-called HER2 overexpression is seen in 15 to 20 percent of breast cancers and is a good predictor of benefit from treatment with trastuzumab (Herceptin), a monoclonal antibody against HER2. It may also correlate with the response to other treatments and to the overall prognosis. Another tumor marker, Oncotype DX, is a multi-gene assay that was developed as a prognostic tool for women with estrogen receptor-positive, lymph node-negative breast cancer.

Current evidence

Prospective studies have shown that women with HER2-positive breast cancer can decrease their risk of recurrence and death by between one-third and one-half by using trastuzumab. Many clinical practice guidelines and health system guidance documents now routinely approve HER2 testing and trastuzumab treatment for women with recurrent breast cancer. Prospective studies of Oncotype DX are less common. It is less widely used as a prognostic tool, although it is approved by some health systems and has been shown to affect the management of patients with early-stage breast cancer.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
×

Issues needing research, and conclusions

Three important characteristics of all tumor markers are their utility (when and how they are used: risk determination, malignancy, prognosis, response to therapy, etc.); the proven magnitude of their effect (the differences in outcome seen in marker-positive and marker-negative patients); and their reliability (measurement standardization, accuracy, and repeatability). Generally, the strongest evidence is gathered from prospective studies in which markers are used to determine treatment or other allocation groups, although retrospective analysis can also produce valid results. Depending on the marker being evaluated, either prospective studies or retrospective analyses will be needed to assess whether the marker should be used in clinical care. Such comparative research is needed for all new genetic markers that are introduced.

References

Andre, F., J. Domont, and S. Delaloge. 2007. What can breast cancer molecular sub-classification add to conventional diagnostic tools? Annals of Oncology 18(Suppl 9):ix33-36.

Carney, W. P., R. Neumann, A. Lipton, et al. 2003. Potential clinical utility of serum HER-2/neu oncoprotein concentrations in patients with breast cancer. Clinical Chemistry 49:1579-1598.

Chiuri, V. E., G. Leo, and V. Lorusso. 2007. Clinical and therapeutic perspectives of gene expression profiling for breast cancer. Annals of Oncology 18(Suppl 6):vi5856-5862.

Dendukuri, N., K. Khetani, M. McIsaac M, et al. 2007. Testing for HER2-positive breast cancer: A systematic review and cost-effectiveness analysis. Canadian Medical Association Journal 176:1429-1434.

Dhesy-Thind, B., K. I. Pritchard, H. Messersmith, et al. 2008. HER2/neu in systemic therapy for women with breast cancer: A systematic review. Breast Cancer Research and Treatment 109:209-229.

Hayes, D. F., A. D. Thor, L. G. Dressler, et al. 2007. HER2 and response to paclitaxel in node-positive breast cancer. New England Journal of Medicine 357:1496-1506.

Henry, N. L., and D. F. Hayes. 2006. Uses and abuses of tumor markers in the diagnosis, monitoring, and treatment of primary and metastatic breast cancer. The Oncologist 11:541-552.

Ross, J. S., J. A. Fletcher, K. J. Bloom, et al. 2004. Targeted therapy in breast cancer. Molecular and Cellular Proteomics 3:379-398.

Seidenfeld, J., D. J. Samson, B. M. Rothenberg, et al. 2008. HER2 Testing to Manage Patients with Breast Cancer or Other Solid Tumors. Evidence Report/Technology Assessment No. 172. AHRQ Publ No. 09-E001. Rockville, MD: Agency for Healthcare Research and Quality.

Valabrega, G., F. Montemurro, and M. Aglietta. 2007. Trastuzumab: Mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Annals of Oncology 18:977-984.

Wolff, A. C., M. E. H. Hammond, J. N. Schwartz, et al. 2007. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for Human Epidermal Growth Factor Receptor 2 testing in breast cancer. Journal of Clinical Oncology 25:118-145.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
×

Drug Treatment of Depression in Primary Care

Brief description of the condition or problem

Lifetime prevalence of depression is up to 17 percent in community surveys; the prevalence of major depression in primary care settings is between 6 and 8 percent. Depression leads to much disability and high utilization of health care, and depression is ranked by the World Health Organization as the fourth leading cause of worldwide disease burden. Suicide occurs in 3.5 percent of depressed patients, an increase of up to 20 times the general population rates. Depression also contributes to increased morbidity and mortality from other medical disorders, such as cardiovascular disease and diabetes. Depression is a chronic and recurring disease in most patients, which contributes greatly to its heavy disease burden.

Available treatments or interventions

Depression is treated most commonly with psychotherapy and drugs. Because of the lack of availability and the cost of psychotherapy in primary care, most primary care patients with depression are treated with drugs. Two major classes of drugs are used: older (and less costly) tricyclic antidepressants (TCAs); and newer (and more costly) agents, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs).

Current evidence

While most patients with clinical depression are seen in primary care settings, most research on depression treatment has been conducted in patients referred from psychiatrists and psychiatric emergency departments—that is, specialty care settings. Research in primary care has found that both TCAs and SSRIs are more effective than placebos in treating depression. Research assessing the newer agents in primary care has found no consistent benefit of one drug over others in terms of efficacy or adverse effects. It is difficult to draw clinically meaningful guidelines for drug choice from the current studies. In addition, many studies are of demographically homogeneous populations and thus do not allow conclusions about depressed patients who are members of minority groups or in the adolescent or elderly age groups.

Issues needing research, and conclusions

Large, head-to-head randomized trials with heterogeneous primary care populations of depressed patients are needed to better understand the benefits and harms of the various antidepressant agents. Observational studies using large databases may provide some of the needed evidence, but without randomization, conclusions may be difficult to obtain.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
×

References

Arroll, B., S. Macgillivray, S. Ogston, et al. 2005. Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: A meta-analysis. Annals of Family Medicine 3:449-456.

Cipriani, A., P. Brambilla, T. A. Furukawa, et al. 2005. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database of Systematic Reviews, Issue 4. DOI: 10.1002/14651858.CD004185.pub2.

Culpepper, L. 2006. Chronic depression: Treatment in primary care. Primary Care Companion to the Journal of Clinical Psychiatry 8:104-105.

Culpepper, L. 2006. Managing depression in primary care. Primary Care Companion to the Juornal of Clinical Psychiatry 8:88-92.

Kroenke, K., S. L. West, R. Swindle, et al. 2001. Similar effects of paroxetine, fluoxetine, and sertraline in primary care: A randomized trial. JAMA 286:2947-2955.

Pignone, M., B. N. Gaynes, J. L. Rushton, et al. 2002. Screening for Depression. Systematic Evidence Review No. 6. AHRQ Publication No. 02-S002. Rockville, MD: Agency for Healthcare Research and Quality.

Simon, G. 2001. Choosing a first-line antidepressant. JAMA 286:3003-3004.

Williams, J. W., C. D. Mulrow, E. Chiquette, et al. 2000. A systematic review of newer pharmacotherapies for depression in adults: Evidence review summary. Annals of Internal Medicine 132:743-756.

Drug Treatment of Epilepsy in Children

Brief description of the condition or problem

Although individual seizures are relatively common in children, epilepsy as an ongoing challenge is less so. A heterogeneous group of disorders characterized by spontaneous, recurrent seizures, epilepsy affects somewhere between 4 and 8 per 1,000 children. Epileptic conditions in childhood vary in diagnostic criteria, management, and clinical outcomes, and many of them are distinct from adult epilepsies as well. Also, drug treatment in children is different from that in adults because their pharmacokinetics vary with age.

Available treatments or interventions

Until the 1990s, six major anticonvulsant drugs were available for children: phenobarbital, phenytoin, carbamazepine, valproic acid, ethosuximide, and the benzodiazepines. These traditional drugs were not optimal because many children with epilepsy did not have their seizures controlled by them or had significant side effects. In the last decade, 10 or more new anticonvulsant drugs have been approved for use in the United States, including felbamate, fosphenytoin, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, and zonisamide. Their indications vary by seizure type or epileptic syndrome and mode of delivery.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Current evidence

Considerations when selecting anticonvulsant drugs in children include seizure type, side effects, mechanism of action, potential drug interactions, pharmacokinetic profile, ease of initiation, need for laboratory monitoring, and cost. In general, there is no evidence that any of the newer anticonvulsant drugs are more efficacious than the traditional drugs in preventing seizures. They often do, however, offer improved pharmacokinetic profiles, fewer drug-drug interactions, and/or better tolerability than the older treatments, albeit at a much higher price. Guidelines from authorities have varied in their recommendations for use of the newer drugs. Some recommend consideration of some of the newer drugs for initial treatment of new onset partial epilepsy, for instance, while other guidelines state that they should be used only when older drugs are ineffective, result in intolerable adverse affects, or are contraindicated.

Issues needing research, and conclusions

Prospective head-to-head trials among the newer anticonvulsant drugs and with traditional drugs among children with similar epileptic disorders are needed, along with careful assessment of side effects and drug-drug interactions. It is unlikely these data can be obtained from case series or analysis of existing treatment data.

References

Connock, M., E. Frew, B.-W. Evans, et al. 2006. The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. Health Technology Assessment 10:1-118.

Donner, E. J., and C. Snead. 2005. New drugs in the treatment of epilepsy in children. Current Problems in Pediatric and Adolescent Health Care 35:398-419.

Marson, A. G., R. Appleton, G. A. Baker, et al. 2007. A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. Health Technology Assessment 11:1-102.

NICE (National Institute for Health and Clinical Excellence). 2004. Newer Drugs for Epilepsy in Children. Technology Appraisal 79. Online. Available at www.nice.org.uk/TA079guidance. Accessed December 2006.

Wheless, J. W., D. F. Clarke, A. Arzimanoglou, et al. 2007. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disorders 9:353-412.

Gamma Knife Surgery for Multiple Types of Intracranial Lesions: Comparison with Surgery and/or Whole Brain Radiation

Brief description of the condition or problem

Gamma knife surgery (GKS) is a type of stereotactic radiation treatment developed in the 1960s. It delivers a high dose of radiation to a lesion in a single session (hence “surgery”) by converging multiple beams of ionizing radiation on a carefully targeted area, with minimal radiation exposure

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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to surrounding areas. The resulting radiation injury to targeted cells’ DNA results in the desired effect, e.g., cell death or decreased growth.

Available treatments or interventions

Traditionally, GKS has been used for small (<4 cm), isolated intracranial lesions or tumors. For example it is used as primary treatment for trigeminal neuralgia, arteriovenous malformations (AVMs), and acoustic neuromas. More recently it has been employed to treat brain metastases and as adjunctive treatment (to surgery and whole-brain radiation) for malignant tumors such as glioblastoma multiforme. GKS has been used to treat movement disorders such as Parkinson’s disease.

Current evidence

GKS is intuitively appealing, given that it is noninvasive (does not require craniotomy) and is generally less costly than brain surgery for the equivalent procedure. That said, very few randomized trials have been performed comparing GKS to conventional surgical, microsurgical, or radiation treatments. For example, a systematic review of GKS in the treatment of trigeminal neuralgia found 23 case series but no randomized trials.

Whereas GKS has become an accepted treatment for certain types of small intracranial lesions, the need for randomized evidence is made clear by the experience with GKS as adjunctive treatment for malignant, infiltrative tumors such as glioblastoma multiforme. While a retrospective case series presented significant benefits of adding GKS to surgery and conventional radiation therapy, when a randomized trial was performed comparing the two strategies no differences in survival outcomes were found.

Issues needing research, and conclusions

The experience with GKS is an example of the general point that technologies require comparative evidence before they are adopted for new indications. A successful track record in treating one condition combined with case series of use for new indications does not add up to compelling evidence for the new use. Comparative research is necessary to insure that simple “technology creep” is not occurring. Thus, head-to-head trials—with whatever treatment is currently the standard—are necessary before new indications for GKS are routinely approved.

References

Borcsek, B., I. Boncz, C. Dozsa, et al. 2005. Systematic literature review of the gamma knife. Italian Journal of Public Health 2:178.

Chamberlain, M. C. 2006. Treatment options for glioblastoma. Neurosurgical Focus 20(4): E2.

Crowley, R. W., N. Poutatian, and J. P. Sheehan. 2006. Gamma knife surgery for glioblastoma multiforme. Neurosurgical Focus 20(4):E17.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Gilbert, M. R. 2006. New treatments for malignant gliomas: Careful evaluation and cautious optimism required. Annals of Internal Medicine 144:371-373.

Lim, J. N. W., and L. Ayiku. 2004 (January). The clinical efficacy and safety of stereotactic radiosurgery (gamma knife) in the treatment of trigeminal neuralgia.

Medicare Services Advisory Committee. 2007. Gamma knife radiosurgery. Medicare Services Advisory Committee:117.

NICE (National Institute for Health and Clinical Excellence). 2004. Stereotactic Radiosurgery for Trigeminal Neuralgia Using the Gamma Knife. Interventional Procedure Guidance 85. Online. Available at http://www.nice.org.uk/nicemedia/pdf/ip/IPG085guidance.pdf.

Nwokedi, E. C., S. J. DiBiase, S. Jabbour, et al. 2002. Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme. Neurosurgery 50:41-47.

Souhami, L., W. Seiferheld, D. Brachman, et al. 2004. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme. International Journal of Radiation Oncology Biology Physics 60:853-860.

Yamakami, I., Y. Uchino, E. Kobayashi, et al. 2003. Conservative management, gamma-knife radiosurgery, and microsurgery for acoustic neurinomas: A systematic review of outcome and risk of three therapeutic options. Neurological Research 25:682-690.

Inguinal Hernia Repair: Open vs. Minimally Invasive

Brief description of the condition or problem

Inguinal hernias, protrusions of the peritoneum (with or without abdominal contents) through a defect or weakness in the abdominal wall, are very common in men, with about a 25 percent lifetime risk. Thus, surgical hernia repair is one of the most common operations in general surgery.

Available treatments or interventions

For more than 100 years, inguinal hernia surgery was an open procedure with general or (more recently) regional or local anesthesia, although the surgical approach has varied over time. Traditional methods of hernia repair used sutures to close the defect. Newer open techniques involve inserting synthetic mesh in an attempt to decrease recurrent hernias. More recently, minimally invasive surgery techniques, using laparoscopic instruments, have been introduced. The two major laparoscopic approaches are transabdominal pre-peritoneal (TAPP) surgery, in which mesh is inserted through the peritoneum to prevent herniation, and totally extraperitoneal repair (TEP), in which the peritoneum is not entered, and the mesh is used to seal the hernia from the outside.

Current evidence

Evidence and practice clearly favor the use of mesh for open and laparoscopic repairs, mainly for reduced recurrence rates. Randomized trials have found that laparoscopic repairs take longer and are more expensive to

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
×

perform than open repairs and require general rather than local or regional anesthesia. Recovery is quicker with laparoscopic surgery, and there is less persisting pain and numbness at the surgical site. There is a question of whether laparoscopic surgery has a higher serious complication rate than open surgery, and the recurrence rate may be higher with laparoscopic surgery. Few randomized trials have compared TAPP vs. TEP techniques, but the newer TEP is technically more difficult to perform than TAPP and takes longer. Both types of laparoscopic surgery are performed more rapidly as surgeons gain experience with the technique used. Because the peritoneum is not entered, the TEP technique may reduce the risk of damage to intra-abdominal organs.

Issues needing research, and conclusions

Because of the necessity for a learning curve for laparoscopic techniques, combining results from earlier trials may not reflect current outcomes. Large-scale data analysis may answer the question of whether laparoscopic hernia repair is more effective and more cost-effective than open repair. If it does not, then a large randomized trial needs to be undertaken. Also, large trials with long-term follow-up are needed comparing the two major laparoscopic approaches, TAPP and TEP.

References

Gokalp, A., M. Inal, G. Maralcan, et al. 2003. A prospective randomized study of Lichtenstein open tension-free versus laparoscopic totally extraperitoneal techniques for inguinal hernia repair. Acta Chirurgica Belgica 103:502-506.

Gould, J. 2008. Laporoscopic versus open inguinal hernia repair. Surgical Clinics of North America 88:1073-1081.

Den Hartog, D., A. H. M. Dur, W. E. Tuinebreijer, et al. 2008. Open surgical procedures for incisional hernias. Cochrane Database of Systematic Reviews, Issue 3. DOI: 10.1002/14651858.CD006438.pub2.

McCormack, K., B. L. Wake, C. Fraser, et al. 2005. Transabdominal pre-peritoneal (TAPP) versus totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair: A systematic review. Hernia 9:109-114.

McCormack, K, N. Scott, P. M. Go, et al. 2003. Laparoscopic techniques versus open techniques for inguinal hernia repair. Cochrane Database of Systematic Reviews, Issue 1. DOI: 10.1002/14651858.CD001785.

NICE (National Institute for Health and Clinical Excellence). 2004. Laparoscopic Surgery for Inguinal Hernia Repair. Technology Appraisal Guidance 83. Online. Available at www.nice.org.uk/TA083guidance. Accessed September 2007.

Scott, N., P. M. Go, P. Graham, et al. 2001. Open mesh versus non-mesh for groin hernia repair. Cochrane Database of Systematic Reviews, Issue 3. DOI: 10.1002/14651858. CD002197.

Wake, B. I., K. McCormack, and C. Fraser. 2005. Transabdominal pre-peritoneal (TAPP) vs totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair. Cochrane Database of Systematic Reviews, Issue 1. DOI: 10.1002/14651858.CD004703.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Outcomes of Percutaneous Coronary Interventions Performed in Hospitals with and without Onsite Surgical Backup

Brief description of the condition or problem

More than 1 million Americans have a myocardial infarction—heart attack—each year, with about a 40 percent mortality rate. Urgent or primary percutaneous coronary intervention (PCI) by cardiac catheterization is recommended in the setting of an ST-segment elevation myocardial infarction [STEMI]), in order to dilate occluded coronary arteries and improve blood flow. More than 1 million PCIs are performed annually in the United States, both in the treatment of STEMI and on an elective basis.

Available treatments or interventions

In the setting of an acute myocardial infarction, establishing cardiac reperfusion as soon as possible is critically important. With a STEMI, PCI has been shown to be superior to pharmacologic reperfusion (fibrinolytic therapy) if undertaken within 90 minutes of first medical contact. Over 90 percent of primary PCIs are successful. In a small number of unsuccessful cases, however, urgent cardiac surgery is required. PCI can be performed in hospitals with and without cardiac surgery capabilities, and many hospitals (especially in suburban and rural areas) have cardiac catheterization facilities but do not have cardiac surgery onsite. Patients prefer care in their local hospitals, and in many cases hospitals with cardiac surgery capabilities are too distant for immediate access. The question is thus whether it is necessary to have cardiac surgery immediately available onsite for primary PCI and/or for elective PCI.

Current evidence

Numerous case series and case-control studies have shown that PCI can be done safely in selected individual hospitals without onsite cardiac surgery. In these studies, PCI success rates and mortality rates are similar to those at hospitals with onsite surgery. An analysis of national Medicare data for patients aged 65 and older, however, found greater mortality for elective PCIs at hospitals without onsite surgery, and elective PCIs are much more common than primary PCIs. As with many procedures, outcomes are usually better in centers with higher volume, once corrected for case mix. Evidence-based guidelines currently recommend that primary PCI may be allowed in hospitals without onsite cardiac surgery if there is a proven process for emergency transport and if the operator and facility meet standards of performance and volume. These guidelines recommend against performance of elective PCI at hospitals without cardiac surgery onsite.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
×

Issues needing research, and conclusions

Studies are needed to assess the safety and outcomes of PCI performed in settings with and without onsite cardiac surgery, both for primary and elective interventions. What facilities, training, procedure volumes, and transport capabilities are necessary for excellent outcomes? Retrospective analysis of national data, if it includes patients under 65 years of age, might provide needed answers. Given excellent results in specific centers without onsite surgery, a randomized, controlled trial would be ethical and would provide more definitive guidance.

References

Canadian Cardiovascular Society, American Academy of Family Physicians, American College of Cardiology, et al. 2008. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction. Journal of the American College of Cardiology 51:210-247.

Frutkin, A. D., S. K. Mehta, T. Patel, et al. 2008. Outcomes of 1,090 consecutive, elective, nonselected percutaneous coronary interventions at a community hospital without onsite cardiac surgery. American Journal of Cardiology 101:53-57.

King, S. B. 3rd, S. C. Smith Jr., J. W. Hirshfeld Jr., et al. 2008. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention. Journal of the American College of Cardiology 51:172-209.

Roussanov, O., G. Sestacio, M. Capuno, et al. 2006. Nonemergent percutaneous coronary interventions in a Veterans Affairs medical center without onsite cardiac surgery. American Heart Journal 152:909-913.

Ting, H. H., G. Raveendran, R. J. Lennon, et al. 2006. A total of 1,007 percutaneous coronary interventions without onsite cardiac surgery. Journal of the American College of Cardiology 47:1713-1721.

Weaver, W. D. 2004. Is onsite surgery backup necessary for percutaneous coronary interventions? JAMA 292:2014-2016.

Wennberg, D. E., F. L. Lucas, and A. E. Siewers. 2004. Outcomes of percutaneous coronary interventions performed in a center without and with onsite coronary artery bypass graft surgery. JAMA 292:1961-1968.

Over-the-counter Drug Treatment of Upper Respiratory Tract Infections in Children

Brief description of the condition or problem

The average child in the United States has 6 to 8 upper respiratory infections (URIs) or colds annually, more if enrolled in day care. URIs are overwhelmingly self-limiting, viral infections, lasting up to 10 days and producing symptoms that include sneezing, cough, rhinorrhea, and fever. Nonprescription, over-the-counter (OTC) cough and cold medications are widely used for children in the United States, with about 4 million children younger than 12 years being treated each week. U.S. sales of OTC cough and cold medicines have been estimated to be at least $3.5 billion annually.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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About 95 million packages of such medication are purchased each year for use by children.

Available treatments or interventions

More than 100 different OTC cough and cold preparations are available. They include individual agents and combinations of the following types of drugs: antipyretics, to reduce fever; decongestants, to relieve nasal congestion; antitussives, to reduce cough; and antihistamines and expectorants, to reduce or thin mucous production. Antihistamines are also employed in “nighttime” formulations to induce sleep.

Current evidence

Antipyretics are safe and effective in reducing fever in children when used as directed. Multiple randomized trials of variable quality have evaluated the other OTC medications for cough and cold and have not found clear evidence of efficacy. There is no good evidence for or against the effectiveness of OTC medicines for acute cough in children. Furthermore, there is clear documentation that OTC cough and cold medications can be toxic, even when used as directed. Also, older children have misused the OTC antitussive dextromethorphan in attempts to induce hallucinations.

Issues needing research, and conclusions

Large-scale, simple head-to-head trials of OTC cough and cold medications are needed to establish clearly if they have effectiveness in reducing the severity and/or duration of URI symptoms in children.

References

American Academy of Pediatrics. 1997. Use of codeine- and dextromethorphan-containing cough remedies in children. Pediatrics 99:918-920.

Chang, A. B., and W. B. Glomb. 2006. Guidelines for evaluating chronic cough in pediatrics. Chest 129:260S-283S.

Dart, R. C., I. M. Paul, G. R. Bond, et al. 2008. Pediatric fatalities associated with over the counter (nonprescription) cough and cold medications. Annals of Emergency Medicine. DOI: 10.1016.annemergmed.2008.09.015.

FDA (Food and Drug Administration). 2008. FDA Statement following CHPA’s announcement on nonprescription over-the-counter cough and cold medicines in children. Online. Available at http://www.fda.gov/bbs/topics/NEWS/2008/NEW01899.html.

Ford, J. A. 2009. Misuse of over-the-counter cough or cold medications among adolescents: Prevalence and correlates in a national sample. Journal of Adolescent Health. DOI: 10.1016/j.jadohealth.2008.10.140.

Gunn, V. L., S. H. Taha, E. L. Liebelt, et al. 2001. Tocicity of over-the-counter cough and cold medications. Pediatrics 108(3):e52.

Irwin, K. A. 2007. Use of over-the-counter cough and cold medications in children younger than 2 years. Journal of Pediatric Health Care 21:272-275.

Merenstein, D., M. Diener-West, A. C. Halbower, et al. 2006. The trial of infant response to diphenhydramine. Archives of Pediatric and Adolescent Medicine 160:707-712.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Sharfstein, J. M., M. North M, and J. R. Serwint. Over the counter but no longer under the radar—Pediatric cough and cold medications. New England Journal of Medicine 357:2321-2324.

Smith, S. M., K. Schroeder, and T. Fahey. 2008. Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database of Systematic Reviews, Issue 1. DOI: 0.1002/14651858.CD001831.pub3.

Substance Abuse and Mental Health Services Administration. Office of Applied Studies. 2008. NSDUH Report: Misuse of Over-the-Counter Cough and Cold Medications among Persons Aged 12 to 25. January 10. Rockville, MD: Substance Abuse and Mental Health Services Administration.

Prevention and Treatment of Pressure Ulcers

Brief description of the condition or problem

A pressure ulcer is an area of localized damage to the skin and underlying tissue caused by pressure, shear, friction, and/or moisture. Pressure ulcers are usually caused by skin compression between a bony prominence and an external surface. Most pressure ulcers arise in hospital and nursing home settings, with an incidence rate of up to 5 percent in hospitals. Incidence rises with patient age, length of stay, and physical incapacity. The presence of pressure ulcers in the elderly is associated with a fivefold increase in mortality rate, with inpatient mortality rates as high as 33 percent.

Available treatments or interventions

Preventive interventions include good nutrition, frequent turning of bedbound patients, prevention of contact with excess moisture, pressure relieving beds, bed pads, and chair pads, and frequent repositioning of wheel-chair bound patients. Once pressure ulcers have occurred they can be treated with all of the above plus dressings of various types, multiple types of topical treatments, and antibiotics when appropriate.

Current evidence

There is good evidence supporting most preventive/nursing measures, such as frequent turning of bedbound patients and prevention of excess moisture. Less evidence is available comparing specific types of dressings, cleansing, and treatments for ulcers themselves. Some studies have found no evidence to support ultrasound treatment of pressure ulcers.

Issues needing research, and conclusions

Good randomized trials are needed comparing alternating pressure beds with continuous low-pressure supports. Good trials with adequate sample sizes are needed for wound dressings and cleansing substances.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Newer topical healing agents, such as nerve growth factor, should be compared head to head with other proven treatment methods.

References

American Medical Directors Association. 2008. Pressure Ulcers in the Long-Term Care Setting. Columbia, MD: American Medical Directors Association.

Consortium for Spinal Cord Medicine. 2000. Pressure Ulcer Prevention and Treatment Following Spinal Cord Injury. Washington, DC: Paralyzed Veterans of American.

Grey, J. E., S. Enoch, and K. G. Harding. 2006. Pressure ulcers. BMJ 332:472-475.

Hollisaz, M. T., H. Khedmat, and F. Yari. 2004. A randomized clinical trail comparing hydrocolloid, pheytoin and simple dressings for the treatment of pressure ulcers. BMC Dermatology 4:1-9. Online. Available at www.biomedcentral.com/1471-5945/4/18.

Landi, F., L. Aloe, A. Russo, et al. 2003. Topical treatment of pressure ulcers with nerve growth factor. Annals of Internal Medicine 139:635-641.

Langer, G., A. Knerr, and O. Kuss. 2003. Nutritional interventions for preventing and treating pressure ulcers. Cochrane Database of Systematic Reviews, Issue 4. DOI: 10.1002/14651858.CD003216.

McInnes, E., S. E. M. Bell-Syer, J. A. C. Dumville, et al. 2008. Support surfaces for pressure ulcer prevention. Cochrane Systematic Reviews, Issue 4. DOI:10.1002/14651858. CD001735.pub3.

Moore, Z. E. H., and S. Cowman. 2005. Wound cleansing for pressure ulcers. Cochrane Database of Systematic Reviews, Issue 4. DOI:10.1002/14651858.CD004983.pub2.

NICE (National Institute for Health and Clinical Excellence). 2005. The Prevention and Treatment of Pressure Ulcers. NICE Clinical Guideline 29. Online. Available atwww.nice.org.uk/CG029.

Registered Nurses Association of Ontario. 2002. Assessment and Management of Stage I to IV Pressure Ulcers. Nursing Best Practice Guideline. Toronto, Ontario: Registered Nurses Association.

Royal College of Nursing. 2005. The Management of Pressure Ulcers in Primary and Secondary Care. London: Royal College of Nursing.

Sari, A. B.-A., K. Flemming, N. A. Cullum, et al. 2006. Therapeutic ultrasound for pressure ulcers. Cochrane Systematic Reviews, Issue 3. DOI:10.1002/14651858.CD001275.pub2.

Thomas, D. R. 2003. The promise of topical growth factors in healing pressure ulcers. Annals of Internal Medicine 239:694-695.

Screening Hospital Inpatients for Methicillin-resistant Staphylococcus aureus Infection

Brief description of the condition or problem

Hospital infections take an enormous toll in the United States, leading to nearly 100,000 deaths and added costs of $6.5 billion annually. Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen in hospital infections, thought to be responsible for 18,000 deaths per year in the United States. MRSA is easily transmitted in hospitals and is a frequent cause of hospital outbreaks. Up to 25 percent of hospital inpatients colonized with MRSA will develop infection. MRSA infection is particularly a problem in surgical patients, now accounting for the majority of Staphylo-

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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coccus aureus surgical site infections. MRSA infections are associated with higher morbidity and mortality rates, longer hospital stays, and greater costs than methicillin-sensitive Staphylococcus aureus infections.

Available treatments or interventions

Standard hospital infection control procedures (increased hand washing, room cleaning and disinfection, and isolation of MRSA-infected patients) have the goal of preventing cross-contamination.

Since MRSA-colonized patients are a risk to themselves and others, their timely identification has become a priority in hospitals around the world. One method introduced to decrease the spread of MRSA is termed “active surveillance culturing” (ASC). In ASC, patients’ nares are typically cultured on or before admission to detect MRSA carriers. They can then be treated and/or isolated to prevent infection and spread of the organism.

Until recently, conventional bacteriological culture techniques were used to detect MRSA carrier status, requiring at least 24 hours and usually 2 to 3 days for results. Recently, rapid detection assays for MRSA using polymerase chain reaction (PCR) technology have become commercially available, shortening detection times from days to hours in optimal settings.

Some infection control experts have argued that ASC should become widespread or universal. Some hospital systems require MRSA screening for all hospital patients on admission; others screen only high-risk or surgical patients. State legislatures have also become vocal on this issue, introducing and occasionally passing legislation requiring hospital MRSA screening.

Current evidence

Standard hospital infection control procedures can and have led to decreased MRSA infection rates.

The use of ASC is both expensive and complex and, like all interventions, has adverse effects. While the PCR tests have good sensitivity (about 80 to 90 percent) and excellent specificity (up to 98 percent) they are expensive, costing about five times as much as conventional cultures. When employed on a large scale, the cost implications are enormous, not just for testing but also for downstream costs related to treatment, isolation, and subsequent care. With an increase in identification of MRSA carriers, many more patients will be isolated by being placed on contact precautions, which has negative implications both for the patients’ care and their mental status.

MRSA screening can clearly identify MRSA carriers, and PCR screening can identify carriers more quickly than conventional culture techniques. Although it costs more, PCR screening thus can reduce the number of inap-

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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propriate pre-emptive isolation days while awaiting conventional culture results.

Much of the data supporting ASC comes from single hospital intervention descriptions, in which screening is part of an overall infection control program and there are no control patients for comparison. Recently published randomized trials of rapid screening tests have reported mixed results, confirming the ability of PCR to identify MRSA carriers quickly but failing to find decreases in MRSA acquisition and/or surgical infection rates resulting from the interventions.

Issues needing research, and conclusions

Despite much research, discussion, and attention, this topic could benefit from further research. Carefully designed controlled trials of various approaches are needed to compare the effects of conventional and rapid MRSA screening with each other and with other infection control measures, such as contact precautions, environmental decontamination, and colonization eradication. Which patient groups will benefit most from screening in MRSA-endemic settings? Will screening decrease overall surgical MRSA infection rates in addition to preventing progression from carrier to infected status in screened individuals? Is there a role for screening in low-prevalence settings? In addition, costs should be evaluated along with effectiveness, given the increased expenses associated with ASC, especially using new rapid assays.

References

Buhlmann, M., K. Bogli-Stuber, S. Droz, and K. Muhlmann. 2008. Rapid screening for carriage of methicillin-resistant Staphylococcus aureus by PCR and associated costs. Journal of Clinical Microbiology 46:2151-2154.

Dancer, S. J. 2008. Considering the introduction of universal MRSA screening. Journal of Hospital Infections 69:315-320.

Diekema, D. J., and M. Climo. 2008. Preventing MRSA infections; finding it is not enough. JAMA 299:1190-1192.

Harbath, S., C. Fankhauser, J. Schrenzel, et al. 2008. Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients. JAMA 299:1149-1157.

Jeyaratnam, D., C. J. M. Whitty, K. Phillips, et al. 2008. Impact of rapid screening tests on acquisition of methicillin resistant Staphylococcus aureus: Cluster randomised crossover trial. BMJ 336:927-930.

Wilcox, M. H. 2008. Rapid screening for MRSA is no more effective at reducing acquisition than conventional screening. BMJ 336:899-900.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Tobacco Cessation: Nicotine Replacement Agents, Oral Medications, Combinations

Brief description of the condition or problem

The use of tobacco products is the leading cause of death in America, resulting in an estimated 440,000 deaths and more than 5 million years of productive life lost annually. Although smoking prevalence has decreased in men from almost 50 percent in the 1950s to 24 percent today, now 19 percent of women smoke, and smoking prevalence is higher in many minority groups and among persons with serious mental illness. Seventy percent of smokers would like to quit, but the combination of nicotine addiction and social habituation makes it difficult for many people to stop smoking.

Available treatments or interventions

In addition to behavioral counseling, which has been shown to enhance quit rates when used with medication, two major categories of pharmaceutical agents have been proven effective: nicotine replacement therapy (NRT) and oral medications. Available nicotine replacement preparations include transdermal patches, gum, inhalers, nasal spray, and lozenges. Oral medications include varenicline and buproprion SR (slow release formulation).

Current evidence

All of the above therapies have been proven superior to placebo in helping smokers quit. Some meta-analyses have shown that certain combinations of therapies (such as nicotine patch combined with gum) are more effective than the patch alone. Based on the pharmacology of the treatments, patient preferences, and clinical experience, guidelines now recommend combining various NRT agents with each other and with oral medications for greatest possible effect.

Issues needing research, and conclusions

Most research has examined single cessation medications with or without behavioral counseling in research settings. Research is needed that compares combinations of drugs, both combinations of NRT agents and the use of NRT agents and oral drugs together. Such head-to-head research is needed in general populations of smokers and for specific subpopulations—women, pregnant women, adolescents, older smokers, individuals with psychiatric disorders, and minority populations. Research should also examine prescription vs. over-the-counter medications and the use of medication combinations with and without counseling from clinicians and in inpatient as well as outpatient settings. Since most evidence is from research settings, effectiveness research from more “real-world” settings is needed.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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References

Bohadana, A., F. Nilsson, T. Rasmussen, et al. 2000. Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation. Archives of Internal Medicine 160:31288-31234.

Cummings, K. M. and A. Hyland. 2005. Impact of nicotine replacement therapy on smoking behavior. Annual Reviews of Public Health 26:583-599.

Fiore, M. C., C. R. Jaèn, T. B. Baker, et al. 2008. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

Hughes, J. R., S. Shiffman, P. Callas, et al. 2003. A meta-analysis of the efficacy of over-the-counter nicotine replacement. Tobacco Control 12:21-27.

Treatment of Acute Thrombotic/embolic Stroke: Clot Removal, Reperfusion Drugs

Brief description of the condition or problem

Almost 800,000 strokes occur each year in the United States, leading to almost $70 billion in direct and indirect costs. Cerebrovascular disease, including stroke, is the third leading cause of death in the United States, resulting in 145,000 deaths in 2005. Of all strokes, about 87 percent are ischemic in origin, meaning that blood flow is obstructed in an artery in the brain. This cuts off the blood supply to the part of the brain supplied by that artery. Most ischemic strokes are caused by a blood clot that forms at the site of obstruction (thrombus) or travels there from the heart (embolus). If the clot is not dissolved or removed, that part of the brain dies and its functions are lost.

Available treatments or interventions

Intravenous tissue plasminogen activator (tPA), which can dissolve thrombi in the setting of an acute thrombotic stroke, is the best-researched and most widely available reperfusion drug. Other, more powerful, or different thrombolytic drugs, such as tenecteplase and reteplase, are available, but not all are FDA approved for use in stroke treatment. Intra-arterial delivery of fibrinolytic agents to the site of the thrombus can potentially expand the time window for reperfusion therapy and decrease the risk of systemic bleeding from the procedure, but it requires more technical capability. Multiple types of percutaneous endovascular therapies are also available for physical clot removal, including clot retrieval devices, suction thrombectomy devices, laser or ultrasound devices, mechanical clot disruption and fragmentation devices, and intracranial angioplasty with or without stents.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Current evidence

Intravenous thrombolytic therapy has been shown to significantly improve acute ischemic stroke outcomes. As a result, all major guidelines recommend that tPA be used in patients with ischemic strokes within 3 hours of the onset of symptoms, assuming lack of contraindications and appropriate facility and clinician experience and capabilities. Despite these guidelines, however, it is estimated that less than 10 percent of stroke patients receive thrombolytic therapy. Reasons include lack of clinical appropriateness, inadequate facilities or inexperienced clinicians, clinician attitudes about the medico-legal consequences of thrombolytic therapy, and delayed presentation or evaluation.

Most of the large number of clot-removal technologies have not been tested in randomized trials. They offer the potential to increase the number of patients with acute stroke who can receive early (but not necessarily restricted to the first three hours) interventions to improve their clinical outcomes.

Issues needing research, and conclusions

Head-to-head trials are needed to compare various thrombolytic agents and percutaneous clot-removal technologies, both individually and combined. The goal is to determine the best strategies for patients, depending on type of stroke, time of presentation, medical comorbidities, and available resources.

References

Adams, H. P. Jr, G. del Zoppo, M. J. Alberts, et al. 2007. Guidelines for the early management of adults with ischemic stroke. Stroke 38:1655-1711.

Albers, G. W., P. Amarenco, J. D. Easton, et al. 2008. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 133(6 Suppl):630S-669S.

American Heart Association. 2009. Heart Disease and Stroke Statistics—2009 update. Dallas, TX: American Heart Association.

Gupta, R., N. A. Vora, and M. B. Horowitz. 2006. Multimodal reperfusion therapy for acute ischemic stroke. Stroke 37:986-990.

Liang, B. A., R. Lew, and J. A. Zivin. 2008. Review of tissue plasminogen activator, ischemic stroke, and potential legal issues. Archives of Neurology 65:1429-1433.

Mielke, O., J. M. Wardlaw, and M. Liu. 2004. Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke. Cochrane Database of Systematic Reviews, Issue 4. DOI:10.1002/14651858.CD000514.pub2.

Molina, C. A., and J. L. Saver. 2005. Extending reperfusion therapy for acute ischemic stroke. Stroke 36:2311-2320.

NICE (National Institute for Health and Clinical Excellence). 2008. Stroke: Diagnosis and Initial Management of Acute Stroke and Transient Ischaemic Attack. NICE Clinical Guideline 68. Online. Available at www.nice.org.uk/CG068.

Stead, L. G., R. M. Gilmore, F. Bellolio, et al. 2008. Percutaneous clot removal devices in acute ischemic stroke. Archives of Neurology 65:1024-1030.

Wardlaw, J. M., G. J. del Zoppo, T. Yamaguchi, et al. 2003. Thrombolysis for acute ischaemic stroke. Cochrane Database of Systematic Reviews, Issue 2. DOI:10.1002/14651858. CD000213.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Treatment of ADHD in Children: Drugs, Behavioral Interventions, no Rx

Brief description of the condition or problem

Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous behavioral disorder characterized by hyperactivity, impulsivity, and inattention. It is the most common behavioral disorder in school-age children, with a prevalence of 8 to 12 percent in the United States. The disorder varies in severity, resulting in mild to severe impairment of daily activities.

Available treatments or interventions

Non-pharmacologic treatments include parental interventions, behavioral interventions, and school interventions. Drug used to treat ADHD include stimulants (both immediate- and modified-release), atomoxetine, and other medications. No treatment is an option as well, especially with milder cases.

Current evidence

Drug therapy is widely regarded as the mainstay of treatment for moderate to severe ADHD, with clear evidence of superiority of all drug types over placebo. Behavioral therapy and other non-pharmacologic treatments have also been shown to be more effective than placebo but have generally not been found to be as good as drug therapy. The combination of drug and non-drug therapy is widely recommended but has rarely been proven to be superior to drug therapy alone. Newer, more expensive extended-release preparations of stimulants and other classes of drugs have been proven effective vs. placebo, but they have not consistently been shown to be better than less expensive immediate-release stimulant formulations. The threshold for the need for drug and/or behavioral treatment is not clearly defined.

Issues needing research, and conclusions

Further research is needed to better define the effectiveness of various behavioral and educational therapies in the overall management of ADHD, in combination with drug therapy. Is behavioral therapy necessary or sufficient treatment for children with mile ADHD? Also, head-to-head trials of immediate- and modified-release stimulants and other medications could better define the relative benefits of these medications in different populations of children and adolescents, especially with respect to costs.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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References

American Academy of Child and Adolescent Psychiatry. 2007. Practice parameter for the assessment of and treatment of children and adolescents with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 46:894-921.

King, S., S. Griffin, Z. Hodges, et al. 2006. A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents. Health Technology Assessment 10:1-162.

Klassen, A., A. Miller, P. Raina, et al. 1999. Attention-deficit hyperactivity disorder in children and youth. Canadian Journal of Psychiatry 44:1007-1016.

McLennan, J. D. 2006. Deciding on stimulant use for childhood ADHD. Canadian Family Physician 52:940-942.

NICE (National Institute for Health and Clinical Excellence). 2008. Attention Deficit Hyperactivity Disorder, NICE Clinical Guideline 72. Online. Available at www.nice.org.uk/CG072.

Smoot, L. C., L. A. Boothby, and R. C. Gillett. 2007. Clinical assessment and treatment of ADHD in children. International Journal of Clinical Practice 61:1730-1738.

Treatment of Chronic Atrial Fibrillation: Drugs, Catheter Ablation, Surgery

Brief description of the condition or problem

Atrial fibrillation (AF), in which the upper chambers of the heart beat in a chaotic unorganized fashion, is the most common heart rhythm abnormality seen in clinical practice, affecting about 2 million Americans. It can lead to blood clots, stroke, heart failure, and increased mortality. Many patients feel fluttering in their chest from AF and are symptomatic from decreased pumping of blood to the body, leading to weakness, dizziness, and/or shortness of breath. Some patients have asymptomatic AF, but they still may be at increased risk of stroke. AF may be paroxysmal, which comes and goes, or chronic, which is persistent.

Available treatments or interventions

Drug treatment includes three types of agents. Anticoagulants such as warfarin and antiplatelet drugs such as aspirin are used to prevent blood clots and strokes. Arrhythmia drugs, including propafenone, flecainide, sotalol, and amiodarone, are intended to prevent the fibrillation rhythm. Drugs in a third group are used to control the fast heart rate that often comes with AF. They include digoxin, various beta-blocker drugs, and some calcium channel blockers. Electrical cardioversion, in which an electric shock is administered to an anesthetized patient, can also convert AF to a regular heart rhythm. Catheter ablation techniques can be used to treat AF without surgery by passing a catheter into the left atrium of the heart and using radiofrequency energy to disrupt the electrical impulses that

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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lead to AF. Finally, open heart surgery can be used to disrupt the electrical impulses, but this is rarely used unless there is another reason (e.g., heart valve repair) for open heart surgery.

Current evidence

Many patients with AF are elderly and have other heart disease problems that complicate their treatment. Others are younger with so-called “lone” AF. Traditionally, the treatment goal was to keep all patients out of AF by using arrhythmia drugs with or without cardioversion. Arrhythmia drugs do not always successfully control heart rhythms, however, and they have major side effects, up to and including mortality. Recent studies have found that many patients, especially elderly, relatively sedentary patients, have similar overall clinical and quality of life-related outcomes with drugs that control heart rate rather than rhythm. Many of these drugs also have fewer side effects than arrhythmia drugs. Some experts recommend rhythm control as an initial strategy for younger, symptomatic patients presenting with AF for the first time and rate control for patients over age 65 with heart disease and who may be unsuitable for electric cardioversion.

Traditionally, catheter ablation was considered only when drug and cardioversion therapy failed. Some recent research, however, mainly in younger patients, has reported high rates of conversion to regular rhythms with catheter ablation, obviating the necessity of years of medications. Long-term follow-up is not yet available for these patients and the studies were done in a small number of highly selected medical centers.

Issues needing research, and conclusions

The costs and effectiveness of catheter ablation in large groups of different populations of patients with AF needs to be determined. As more centers become skilled in catheter ablation techniques, large effectiveness rather than efficacy studies will be useful to determine the best clinical guidance for patients with diverse risk factors and comorbidities. Most likely new, randomized trials will have to be undertaken to answer these questions, as current data are probably unsuitable for systematic review.

References

Andrikopoulos, G., S. Tzeis, N. Maniadakis, et al. 2009. Cost-effectiveness of atrial fibrillation catheter ablation. Europace 11:147-151.

Cox, J. L. 2005. The central controversy surrounding the interventional-surgical treatment of atrial fibrillation. Journal of Thoracic and Cardiovascular Surgery 129:1-4.

Khargi, K., B. A. Hutten, B. Lemke, et al. 2005. Surgical treatment of atrial fibrillation: A systematic review. European Journal of Cardiothoracic Surgery 27:258-265.

Mead, G. E., A. Elder, A. D. Flapan, et al. 2005. Electrical cardioversion for atrial fibrillation and flutter. Cochrane Database of Systematic Reviews, Issue 3. DOI:10.1002/14651858. CD002903.pub2.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Morady, F., H. Oral, F. Pelosi, et al. 2007. The Treatment of Atrial Fibrillation. University of Michigan Electrophysiology Service. Online. Available at http://www.med.umich.edu/1libr/aha/Pt_ed_A1204.pdf.

NICE (National Institute for Health and Clinical Excellence). 2006. Atrial Fibrillation. NICE Clinical Guideline 36. Online. Available at www.nice.org.uk/CG036.

Oral, H., C. Pappone, A. Chugh, et al. 2006. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. New England Journal of Medicine 354:934-941.

Wanzi, O. M., N. F. Marrouche, D. O. Martin, et al. 2005. Radiofrequency ablation vs. antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation. JAMA 293(21):2634-2640.

Wood, M. A., and K. A. Ellenbogen. 2006. Catheter ablation of chronic atrial fibrillation—The gap between promise and performance. New England Journal of Medicine 354:967-969.

Treatment of Chronic Low Back Pain

Brief description of the condition or problem

Acute low back pain serious enough to disrupt daily routines affects about 70 percent of adults sometime during their lives, and it is the second most frequent symptomatic cause for visiting a doctor in the United States. In the vast majority of patients, low back pain resolves within a few weeks with conservative medical management. But about 5 percent of patients go on to have nonspecific chronic low back pain, defined as pain lasting longer than 12 weeks without a specific treatable cause (such as tumor or fracture). These patients experience significant pain and functional impairment and consume 90 percent of all the healthcare costs associated with low back pain.

Available treatments or interventions

The main choice in managing chronic low back pain is whether to continue medical management or undergo spinal surgery.

Medical management can include the following interventions individually or in combination: pain, anti-inflammatory, and other medications; physical and rehabilitation therapy and other types of exercise programs: acupuncture and acupressure: cognitive-behavioral therapy: spinal manipulation: massage: and other treatments.

The mainstay of surgical treatment for nonspecific low back pain is spinal fusion surgery, which can be performed several ways. The intent of the surgery is to stabilize the spine and remove the cause of the chronic low back pain. Between 150,000 and 300,000 spinal fusion surgeries are attempted each year, costing over $16 billion in annual hospital charges.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Current evidence

Most evidence on pharmaceutical treatment of chronic low back pain comes from placebo-controlled trials. Short-term trials have found small to moderate levels of effectiveness for decreasing pain and increasing function for acetaminophen, antidepressants, antiepileptic drugs, benzodiazepines, non-steroidal anti-inflammatory drugs, and opioids. Few head-to-head trials have been conducted. Few trials have included multiple medications, which are commonly prescribed by doctors.

Several non-pharmaceutical therapies show similar effectiveness versus placebo in the treatment of chronic low back pain. These treatments include acupuncture, acupressure, psychological counseling, interdisciplinary rehabilitation, exercise, massage, spinal manipulation, and yoga. Again, few head-to-head trials have been conducted, and trials including multiple interventions are also uncommon.

At least six randomized trials have compared lumbar fusion surgery with some type of intensive nonsurgical management for chronic low back pain, with conflicting results. Questions have been raised about the varying exclusion criteria and generalizability of these studies. Although some patients were clearly helped by the surgery, it is difficult to define the characteristics of patients most likely to benefit.

Issues needing research, and conclusions

For the treatment of chronic low back pain, most published research of drug and non-invasive nondrug therapy is composed of placebo-controlled trials of single treatments. There is a paucity of research of dual-agent treatment, although most patients are treated this way. Also, head-to-head trials are needed to evaluate the relative effectiveness of drug and non-drug treatments for this condition.

But the key need in this area is research on the comparative effectiveness of spinal fusion surgery and nonsurgical approaches. Which types of patients are most likely to benefit from surgery, and when should it be undertaken in the course of the illness? Because of the significant disability associated with chronic low back pain, cost-effectiveness studies are also crucial in helping to decide which approaches return patient function to normal most quickly. Comparative studies are also needed of different surgical approaches and techniques, as well as the appropriate use of procedures such as intradiscal electrothermal therapy and the appropriate role for newer artificial spinal disks.

References

Andersson, G. B. J., N. A. Mekhail, and J. E. Block. 2006. Treatment of intractable discogenic low back pain: A systematic review of spinal fusion and intradiscal electrothermal therapy. Pain Physician 9:237-248.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Chou, R. and L. H. Huffman. 2007. Medications for acute and chronic low back pain: A review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Annals of Internal Medicine 147:505-514.

Chou, R. and L. H. Huffman. 2007. Nonpharmacologic therapies for acute and chronic low back pain: A review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Annals of Internal Medicine 147:492-504.

Deyo, R. A. 2007. Back surgery: Who needs it? New England Journal of Medicine 356:2239-2243.

Fairbank, J., H. Frost, J. Wilson-MacDonald, et al. 2005. Randomised controlled trial to compare surgical stabilization of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: The MRC spine stabilisation trial. BMJ 330:1233-1238.

Henschke, N., C. G. Maher, K. M. Refshauge, et al. 2007. Low back pain research priorities: A survey of primary care practitioners. BMC Family Practice 8:40.

Hsieh, L. L., C. Kuo, L. H. Lee, et al. 2006. Treatment of low back pain by acupressure and physical therapy: Randomised controlled trial. BMJ 332:696-698.

Ibrahim, T., I. M. Tleyjeh, and O. Gabbar. 2008. Surgical versus non-surgical treatment of chronic low back pain: A meta-analysis of randomised trials. International Orthopaedics 32:107-113.

Koes, B. 2005. Surgery versus intensive rehabilitation programmes for chronic low back pain. BMJ 330:1220-1221.

Melloh, M., C. Roder, A. Elfering, et al. 2008. Differences across health care systems in outcome and cost-utility of surgical and conservative treatment of chronic low back pain: A study protocol. BMJ Musculoskeletal Disorders 9:81.

Sherman, K. J., D. C. Cherkin, J. Erro, et al. 2005. Comparing yoga, exercise, and a self-care book for chronic low back pain. Annals of Internal Medicine 143:849-856.

Soegaard, R., F. B. Christensen, T. Christiansen, et al. 2007. Costs and effects in lumbar spinal fusion: A follow-up study in 136 consecutive patients with chronic low back pain. European Spine Journal 16:657-668.

Zeller, J. I. 2006. Artificial spinal disk superior to fusion for treating degenerative disk disease. JAMA 296:2665-2667.

Treatment of Localized Prostate Cancer: Watchful Waiting, Surgery, Radiation, Hormone Therapy, or Cryotherapy

Brief description of the condition or problem

In the United States in 2008, there were an estimated 186,000 new cases of prostate cancer and more than 28,000 deaths from this disease. Prostate cancer is, aside from skin cancers, the leading cause of new cancers and is the second leading cause of cancer deaths in men. However, up to 70 percent of men are found to have cancer in their prostate gland at the time of death, most often in low-grade microscopic amounts that posed no threat to the man during life. Thus, prostate cancer is common, diagnosed in one of six men, but it is fatal in only 3 percent of men. This leads to the perplexing problem of trying to decide which prostate cancers to treat and what treatment to use. Most prostate cancers are now diagnosed by elevated prostate-specific antigen (PSA) levels in routine testing, although

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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some are still detected on clinical examination of the prostate or from patient symptoms.

Available treatments or interventions

Major options for localized prostate cancer include watchful waiting, in which the PSA level is followed and no treatment is given initially; radical prostatectomy, which is usually an option only if the cancer is confined within the capsule of the prostate; radiation therapy, with external-beam radiation or implanted radioisotopes (brachytherapy); hormonal therapy with various anti-androgen hormones; and cryotherapy, in which probes are introduced into the tumor to freeze and kill malignant cells.

Current evidence

No randomized trial data favor one treatment or combination of treatments for prostate cancer over another. Patients and their doctors need to balance limited evidence of treatment efficacy with important known side effects as well as patient preferences and the availability and quality of local services.

If the cancer is confined to the prostate, then surgery offers the chance for a cure and is often offered to younger men, especially if the biopsies show an aggressive tumor. Prostatectomy has significant side effects, however, such as impotence and incontinence. It is not usually done in patients who have cancer that has spread beyond the prostate capsule.

External radiation can be effective in extending survival in men with cancer that has spread locally and is often preceded by hormonal therapy to shrink the tumor mass. It does not require a hospital stay or recuperation from surgery, although it has significant side effects as well, including impotence and rectal irritation and injury. Brachytherapy has fewer side effects because the radiation dose is lower than external beam radiation, but the clinical effectiveness is not as well demonstrated as other types of radiation.

Cryotherapy has not been tested in many randomized trials comparing it to more conventional treatments, and its effectiveness has mainly been documented in case series. Watchful waiting is often employed in older men and those with concomitant serious diseases, or in younger men with relatively low PSA levels and lower-grade tumors. The literature describing its long-term effectiveness is mainly from the pre-PSA era, when cancers were detected by symptoms at a more advanced stage. It, of course, has no side effects and active monitoring allows later treatment when and if it is deemed appropriate.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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Issues needing research, and conclusions

Better understanding is needed of the choice, sequencing, and combination of therapies that are most effective for localized and early prostate cancer, including trials comparing radical prostatectomy and radiation in its various forms, including drug therapy. The role of watchful waiting both in the extremely elderly and in young men with low PSA levels and low-grade tumors needs to be established with clinical trials.

References

Kumar, S., M. Shelley, C. Harrison, et al. 2006. Neo-adjuvant and adjuvant hormone therapy for localized and locally advanced prostate cancer. Cochrane Database of Systematic Reviews, Issue 4. DOI:10.1002/14651858.CD006019.pub2.

NCI (National Cancer Institute). 2008. National Cancer Institute Prostate Cancer Treatment (PDQ), Health Professional Version. Online. Available at http://www.cancer.gov/cancertopics/pdq/treatment/prostate/healthprofessional.

Postma, R.. 2006. Treatment of prostate cancer. Annals of Oncology 17(suppl 10), x207-210. DOI: 10.1093/annonc/mdl261.

Shelley, M., T. Wild, B. Coles, et al. 2007. Cryotherapy for localised prostate cancer. Cochrane Database of Systematic Reviews, Issue 3. DOI:10.1002/14651858.CD005010.pub2.

Taichman, R. S., R. D. Loberg, R. Mehra, et al. 2007. The evolving biology and treatment of prostate cancer. Journal of Clinical Investigations 117:2351-2361.

Zeliadt, S. B., S. D. Ramsey, D. F. Penson, et al. 2006. Why do men choose one treatment over another? Cancer 106:1865-1874.

Use of Erythropoiesis-stimulating Agents in the Treatment of Hematologic Cancers

Brief description of the condition or problem

Anemia, a decreased red blood cell count, is common in cancer, occurring in up to two-thirds of patients. It can be caused by the disease itself (due to bone marrow infiltration or hemolysis), by nutritional deficiencies, by the myelosuppressive effects of chemotherapy, or by a combination of these factors. Anemia causes well-documented adverse effects in cancer patients, including weakness, impaired concentration, and, most commonly, fatigue. All of these lead to a decreased quality of life, which has been amply demonstrated in research studies. Anemia may also contribute to decreased responsiveness to radiotherapy or chemotherapy.

Available treatments or interventions

Before the development of erythropoiesis-stimulating agents, transfusions were the treatment of choice for cancer-associated anemia. Although transfusions immediately reverse anemia-related symptoms, the effects are short-lived and do not affect the cause of the anemia. Further, frequent transfusions increase the likelihood of adverse effects such as alloimmu-

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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nization, allergic reactions, iron overload, and transmission of infectious diseases.

Recombinant human erythropoietin was developed to stimulate red cell formation and has been used in a wide range of disorders to treat chronic anemia. It does not increase hemoglobin levels immediately but its effects last longer than transfusions. It is available in two forms, alpha and beta, which are very similar in molecular characteristics and pharmacokinetics. A third erythropoiesis-stimulating agent, darbepoetin alfa, is also available. It is longer acting than erythropoietin and only needs to be given every three weeks.

Current evidence

Numerous randomized and non-randomized trials have established that erythropoiesis-stimulating agents increase hemoglobin levels and reduce transfusion requirements in cancer patients with anemia. They also decrease fatigue and increase quality of life. U.S. clinical practice guidelines recommend that an erythropoiesis-stimulating agent be started as hemoglobin levels reach or fall below 10 g/dL.

Many doctors start erythropoiesis-stimulating agents at higher levels, believing the quality of life is dramatically improved if the hemoglobin levels are kept from going lower than 11 or 12 g/dL. Although there is some research showing that the quality of life is improved when these agents are started earlier, it is controversial.

Recent studies have raised the possibility that erythropoiesis-stimulating agent use may increase the risk for thromboembolism. Thus, patients with standard risk factors for thromboembolic events—history of previous thrombosis, surgery, or prolonged immobilization—may be at increased risk of having a throbolembolic event while taking epoetin or darbepoetin. Questions have also been raised about the effects of erythropoiesis-stimulating agents on mortality rates, with some studies showing positive effects and others (particularly in the treatment of solid tumors, not hematologic malignancies) finding increased mortality.

Issues needing research, and conclusions

Comparative effectiveness research would be helpful in defining the exact benefits, costs, and harms of starting erythropoiesis-stimulating agents at different hemoglobin levels in patients with hematologic malignancies. Head-to-head trials could address the advantages and disadvantages of erythropoietin alpha and beta versus the newer preparation, darbepoetin alfa. Finally, large-scale data collection/registers might be helpful to better understand the risks as well as benefits to cancer outcomes associated with these agents.

Suggested Citation:"Appendix B: Comparative Effectiveness Studies Inventory Project." Institute of Medicine. 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12214.
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References

Aapro, M., A. Scherhag, and H. U. Burger. 2008. Effect of treatment with epoetin-β on survival, tumor progression, and thromboembolic events in patients with cancer: An updated meta-analysis of 12 randomised controlled studies including 2301 patients. British Journal of Cancer 99:14-22.

Bohlius, J., S. Langensiepen, G. Schwarzer, et al. 2005. Recombinant human erythropoietin and overall survival in cancer patients: Results of a comprehensive meta-analysis. Journal of the National Cancer Institute 97:489-498.

Hardee, M. E., M. O. Arcasoy, K. L. Blackwell, et al. 2006. Erythropoietin biology in cancer. Clinical Cancer Research 12:332-339.

Jones, M., B. Schenkel, J. Just, et al. 2004. Epoetin Alfa improves quality of life in patients with cancer: Results of a meta-analysis. Cancer 101:1720-1732.

Oster, H. S., M. Hoffman, S. Pruchti-Sagiv, et al. 2006. Erythropoietin in clinical practice: Current use, effect on survival, and future directions. Israel Medical Association Journal 8:703-706.

Pronzato, P. 2006. Cancer-related anaemia management in the 21st century. Cancer Treatments Reviews 32:S1-S3.

Rizzo, J. D., M. R. Somerfield, K. L. Hagerty, et al. 2008. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update. Journal of Clinical Oncology 26:132-149.

Straus, D. J. 2005. Treatment of anemia with erythropoietic agents in patients with hematologic malignancies. Supportive Cancer Therapies 2:215-224.

Straus, D. J., M. A. Testa, B. J. Sarokhan, et al. 2006. Quality-of-life and health benefits of early treatment of mild anemia: A randomized trial of epoetin alfa in patients receiving chemotherapy for hematologic malignancies. Cancer 107:1909-1917.

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It is essential for patients and clinicians to have the resources needed to make informed, collaborative care decisions. Despite this need, only a small fraction of health-related expenditures in the United States have been devoted to comparative effectiveness research (CER). To improve the effectiveness and value of the care delivered, the nation needs to build its capacity for ongoing study and monitoring of the relative effectiveness of clinical interventions and care processes through expanded trials and studies, systematic reviews, innovative research strategies, and clinical registries, as well as improving its ability to apply what is learned from such study through the translation and provision of information and decision support.

As part of its Learning Health System series of workshops, the Institute of Medicine's (IOM's) Roundtable on Value & Science-Driven Health Care hosted a workshop to discuss capacity priorities to build the evidence base necessary for care that is more effective and delivers higher value for patients. Learning What Works summarizes the proceedings of the seventh workshop in the Learning Health System series. This workshop focused on the infrastructure needs--including methods, coordination capacities, data resources and linkages, and workforce--for developing an expanded and efficient national capacity for CER. Learning What Works also assesses the current and needed capacity to expand and improve this work, and identifies priority next steps.

Learning What Works is a valuable resource for health care professionals, as well as health care policy makers.

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