|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2007.15.0169 on March 31 2008 © 2008 American Society of Clinical Oncology. Individual Physician Practice Variation in Hematopoietic Cell Transplantation
From the Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Pediatrics, Medicine, and Medical Oncology, Dana-Farber Cancer Institute, Children's Hospital, Boston, MA; Department of Medicine, University of Chicago, Chicago, IL; Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, Houston, TX; Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN; Pediatric Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Medicine, University of Nebraska, Omaha, NE; and the Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI Corresponding author: Stephanie Lee, MD, MPH, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D5-290, Seattle, WA 98109; e-mail: sjlee{at}fhcrc.org
Purpose Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT. Methods An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making. Results Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning. Conclusion These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice.
Ideally, patients with similar diseases and clinical situations would obtain the same treatment recommendations and care regardless of the physician they see. If they do not, then "practice variation" exists. Practice variation may be due to controversy over the effectiveness of various procedures1 or differences in physician practice style.2 Undesirable practice variation may result from lack of familiarity with or adherence to evidence-based practice, external nonmedical influences on physicians (eg, practice environment, reimbursement structure),3 or consideration of patient characteristics (eg, race, ethnicity, sex, age, personal resources) if these features should not influence treatment recommendations. Previous studies evaluating practice variation in hematopoietic cell transplantation (HCT) show that transplant activity varies by country4 and is associated with gross national income.5-7 Other studies show that transplant centers vary in their prophylaxis strategies and management of transplant complications.8-13 However, no HCT studies have measured individual physician decision making or explored physician and transplant center characteristics that may be associated with those decisions. Understanding practice variation offers different benefits depending on the strength of the evidence supporting a clinical practice. If evidence is scant, then wide practice variation can identify areas of controversy worthy of study and increase tolerance for practices different from one's own. Potential areas for cost saving can be identified, because in the absence of improved patient outcomes, the least costly approach is justifiable.14 If evidence for a practice is strong, then documentation of practice variation highlights areas where better education, dissemination of information, and quality improvement systems can improve care.15,16 In all cases, appreciation of practice variation can help with planning and interpreting clinical trials. Physician surveys are ideal tools for studying practice variation in a cost efficient and highly controlled manner, because many physicians can be presented with the identical clinical scenario and treatment options.17-20 We conducted an Internet-based survey of transplant physicians to examine practice variation in HCT. Our intent was to document the degree of practice variation attributable to nonpatient factors.
Survey Development A draft survey was prepared by the authors and subsequently modified after pilot testing. The sociodemographic questions were taken from similar studies previously conducted by the authors.12 Individual items were constructed to measure practice variation in medical decision making. The self-administered survey contained 44 to 50 items depending on whether respondents identified themselves as adult or pediatric transplant physicians. The survey took 10 to 20 minutes to complete, and respondents were allowed to skip questions. A copy of the survey may be obtained by contacting the corresponding author. Eight questions presented clinical scenarios and elicited treatment recommendations. Two of the eight clinical scenarios and two questions related to acute and chronic graft-versus-host disease (GVHD) were identical between pediatric and adult versions. Adult transplant physicians were also asked six questions about choice of myeloablative versus reduced intensity conditioning (RIC) in specified situations. Eleven additional questions collected physician and transplant center characteristics. This report focuses on decision making related to indications for transplantation, choice of stem-cell source, and treatment of acute and chronic GVHD in adult and pediatric practice; other data will be reported elsewhere.
Data Collection Two thousand two hundred twenty-nine emails were sent to potentially eligible subjects. Five hundred seventy were not eligible to respond due to confirmation of undeliverable e-mail, duplicate addresses, or confirmation that the recipient was ineligible (for example, not a transplantation physician, retired). Five hundred forty responses were received of which 526 were assessable. Surveys (n = 14) were excluded if respondents answered fewer than one half of the medical decision making or supportive care questions. Only 84 recipients actively declined to participate in the study; 1,035 did not respond in any way to the three emails, and we are unable to further classify this group into passive nonrespondents versus inactive e-mail addresses. Thus, the assessable response rate was somewhere between 32% of all potentially eligible invitations (526 of 1,659) and 84% of confirmed invitations (526 of 624). Two hundred forty-eight responded to the first e-mail (47%), with subsequent emails garnering 147 (28%), 75 (14%), and 56 (11%) of assessable respondents.
Biostatistical Analysis Individual respondents were considered unassessable for particular questions if either they did not answer the question, indicated they did not see those types of patients, or otherwise indicated the question did not pertain to them. Respondents providing write in answers to the "other, specify" option were recategorized into existing response options if appropriate. Within the tables, results are presented if more than 5% of either pediatric or adult transplant physicians endorsed an option. To assess nonresponder bias, physician characteristics and responses to the vignettes were compared between three groups: those responding to the initial e-mail, those responding to the first reminder e-mail, and those responding to either the second or third reminder emails. There were no differences in the distribution of characteristics and responses.
Physician Practice Characteristics Physician and center descriptions are presented in Table 1. Of note, the sample was predominantly male (74%), practiced in an academic center (73%), and was clinically active. The median age was 47 years, and 57% practiced in the United States. Half had completed fellowship before 1991. Three hundred eighty-three (73%) considered themselves adult transplant physicians while 142 (27%) considered themselves pediatric transplant physicians. Adult and pediatric transplant physicians were of similar age and time since training. They reported equal frequencies of being in academic versus community practices and a similar distribution of time spent in administration and teaching, basic, and clinical research. However, pediatricians were more likely to be women (38% v 19%; P < .0001) and to practice in the United States (70% v 54%; P = .0015). Pediatricians spent less time in clinical care (P = .01), had less clinic (P < .0001) and ward time (P = .01), and reported smaller transplant practices (P < .0001) with a greater percentage of myeloablative allogeneic procedures.
Medical Decision Making Tables 2,3,4,and 5 summarize answers to the scenarios posed to adult and pediatric transplant physicians. Specifically, Table 2 compares adult and pediatric physicians' responses to identical vignettes (except in one case where the patient's age differed by 5 years). Pediatricians were more likely than adult transplant physicians to recommend allogeneic transplantation to an 18-year-old with chronic phase chronic myeloid leukemia (CML) and an HLA-matched sibling (70% v 35%; P < .0001). Pediatricians were somewhat more likely than adult transplant physicians to recommend an alternative chemotherapy regimen for a 20-year-old with resistant blast crisis CML (50% v 38%); adult transplant physicians, in contrast, were more likely to endorse allogeneic HCT while in blast crisis or best supportive care. Pediatricians favored bone marrow over peripheral blood as a stem-cell source for young patients undergoing matched sibling transplantation for aplastic anemia compared with adult transplant physicians (90% v 68%; P < .0001). The fact that 32% of adult transplant physicians recommended peripheral blood over bone marrow for young patients with aplastic anemia is surprising given reports suggesting good outcomes with bone marrow and higher chronic GVHD and mortality with peripheral blood.22,23 When choosing therapy for steroid-refractory acute GVHD where there is no established standard of care, there was little agreement in either group, with no agent garnering more than 21% of the vote. Pediatricians favored infliximab (21%), higher dose steroids (15%), horse antithymocyte globulin (ATG; 14%), daclizumab (13%), and mycophenolate mofetil (MMF; 13%) compared with adult physicians who favored MMF (20%), rabbit ATG (18%), and horse ATG (14%). Although approximately half of both adult and pediatric transplant physicians selected MMF as the next agent for steroid-refractory chronic GVHD, pediatricians also endorsed higher dose steroids (16%), calcineurin inhibitors (7%), and pentostatin (7%) while adult transplant physicians favored calcineurin inhibitors (12%), extracorporeal photopheresis (10%), and sirolimus (7%) instead. When tapering steroids after successful control of chronic GVHD, pediatricians waited longer before initiating a taper.
Table 3 summarizes the results of scenarios posed only to adult transplant physicians. The lack of clear consensus for most of the situations is notable. The role of autologous and allogeneic hematopoietic transplantation in multiple myeloma, is particularly controversial. Forty-one percent of physicians endorsed autologous transplantation followed by RIC allogeneic transplantation for a patient with chemotherapy-sensitive myeloma even though this is the focus of an ongoing Clinical Trials Network study and a recent high profile publication.24 When all options offered dismal outcomes (a 25-year-old with relapsed acute lymphoblastic leukemia and persistent disease after one attempt at reinduction), physicians were evenly divided over proceeding directly to transplantation (53%) or attempting another induction regimen (46%). Table 4 summarizes responses to the pediatric scenarios. As observed among adult transplant physicians, pediatric transplant physicians also differed in their responses to the clinical scenarios presented. Approximately 50% of physicians recommended a matched related donor transplant for a patient with low-risk AML although several published reports indicate comparable outcomes with the intensified chemotherapy regimens used in the current era.25,26 When faced with a patient with high-risk AML, continuing chemotherapy was preferred by one fourth of respondents over an allele-matched unrelated donor transplant although several reports support the later treatment when a well-matched unrelated donor is available.27,28 Table 5 presents data regarding choice of myeloablative or RIC for specific scenarios where an HLA-matched sibling is available. For five of six questions regarding RIC, respondents who identified themselves primarily as RIC transplant physicians (n = 54) were more likely to recommend RIC than myeloablative transplant physicians (n = 175). Review of the responses to the six scenarios suggests that disease type is the primary determinant of conditioning regimen choice, although older age and poor performance status also appear to favor RIC. RIC allogeneic transplantation is a rapidly developing area in which the indications are not well established and multiple different regimens are under study. Table 6 presents the physician and transplant center characteristics predictive of selected medical decisions. Several physician and practice factors were associated with medical decision making. However, in multivariate models accounting for these other factors, pediatricians were still more likely to recommend HLA-matched sibling transplantation instead of continued imatinib for an 18-year-old with chronic phase CML, and bone marrow instead of peripheral blood for a patient with aplastic anemia. Among pediatricians, transplant physicians in the United States were more likely to recommend HLA-matched sibling transplantation instead of chemotherapy for an 11-year-old girl with t(8;21) in first complete remission.
We found considerable variation in medical decision making among adult and pediatric HCT physicians participating in the CIBMTR. Our results suggest that similar patients are receiving different treatment recommendations across physicians and centers, likely reflecting a paucity of robust clinical trials on which to base uniform clinical decision making. One area of striking variation is the differential recommendations of adult and pediatric transplant physicians when presented with identical scenarios involving adolescents and young adults. In the specific case of whether to recommend imatinib or transplantation for chronic phase CML, reluctance among pediatric transplant physicians to apply data derived from studies among adults to the treatment of older pediatric patients, or greater concern about unknown long-term effects of tyrosine kinase inhibitors, may help explain the observed differences in treatment recommendations. Differences in pediatric and adult decision making persisted in multivariate models that simultaneously adjusted for other physician and transplant center characteristics such as age, sex, center size, and center location. Our data confirm that management of steroid-refractory acute and chronic GVHD is highly variable among both adult and pediatric physicians. Pediatricians tend to use higher dose steroids to treat steroid-refractory acute and chronic GVHD, and to wait longer before tapering steroids in chronic GVHD, than do adult transplant physicians. Older patients may have more complications with corticosteroids, such as myopathy and avascular necrosis of bone, leading their physicians to minimize dosing as soon as possible. Several studies utilizing surveys have assessed practice variation among transplant centers. Wide practice variation has been noted in dimethylsulfoxide autologous cryopreservation protocols,8 approaches to prophylaxis and treatment of acute GVHD,9 definitions of steroid-refractory acute GVHD and salvage treatment regimens,10 infectious prophylaxis and compliance with published guidelines,11 and diagnosis and management of chronic GVHD.12 However, only Rutuu and colleagues13 have attempted to compare reported practices with actual patient outcomes. This group compared reported center practices for handling steroid-refractory acute GVHD with the actual outcomes of CML patients developing GVHD at the centers. They reported better outcomes when lower dose steroids were used for initial acute GVHD treatment,13 consistent with findings from a randomized clinical trial.29 We acknowledge several limitations of the data presented herein, and emphasize that this study was an exploratory analysis of practice variation within the field of HCT. First, because of difficulties in defining the denominator of eligible physicians, the true response rate to the survey was somewhere between 32% and 84%. Based on the CIBMTR's update of its database in 2007, many e-mail addresses we used were likely to have been defunct or to have reached individuals who were ineligible to participate. Although we requested that people opt-out, we do not have any true estimate of the actual denominator of eligible respondents reached. The literature suggests that an average physician survey achieves a response rate of 54%.30 The second limitation is that we asked participants to answer based on what they "usually do with most" of their patients. Respondents were forced to choose their one best answer to the vignette without opportunity to learn additional clinical information. Although surveys are a common approach to measuring practice variation,17-19,31,32 they are one step removed from measuring actual practices.15 They do, however, have the advantage of ensuring that all physicians are working with identical data. Studies comparing vignettes with standardized patients (actors hired to impersonate real patients) and chart review suggest that vignettes can accurately reflect actual practice patterns and are much more cost-effective.33,34 The third limitation is that due to our concern about the length of the survey and ensuring responder anonymity, we can not elaborate further on many of our findings. For example, we did not collect data about institutional affiliations to explore whether medical decision making was consistent within practice groups. We do not know if transplant physicians were following institutional practice guidelines or practicing autonomously. Finally, and perhaps most importantly, several of the scenarios chosen were purposefully controversial without clear evidence to suggest one optimal approach. Nevertheless, we believe this survey should encourage HCT physicians to question whether the degree of practice variation within the field is desirable. It also suggests there is significant selection bias in who is offered a HCT, in the type of HCT offered, and how post-HCT complications are managed, implying that a careful characterization of these factors is important in interpreting reported observational and single-institution data. Even randomized studies could be affected by practice variation if the randomization does not balance important clinical management characteristics. Our results also have implications for clinical practice since they provide additional support for the observation that patients often receive different recommendations and treatment from different practitioners.4,35-37 It is important that practice variation be discussed with the patient who is "shopping around," especially when such variation results from lack of data. Finally, we believe that the practice variation documented here should encourage the design and implementation of randomized clinical trials to address controversial areas of HCT practice. Where clinical trials are not feasible, rigorous observational data may provide the best available evidence to guide practice.
The author(s) indicated no potential conflicts of interest.
Conception and design: Stephanie J. Lee, Steven Joffe, Andrew S. Artz, Stella M. Davies, Nancy A. Kernan, Mary Eapen Collection and assembly of data: Stephanie J. Lee Data analysis and interpretation: Stephanie J. Lee, Steven Joffe, Andrew S. Artz, Richard E. Champlin, Stella M. Davies, Madan Jagasia, Nancy A. Kernan, Fausto Loberiza Jr, Robert J. Soiffer, Mary Eapen Manuscript writing: Stephanie J. Lee, Steven Joffe, Andrew S. Artz, Richard E. Champlin, Stella M. Davies, Madan Jagasia, Nancy A. Kernan, Fausto Loberiza Jr, Robert J. Soiffer, Mary Eapen Final approval of manuscript: Stephanie J. Lee, Steven Joffe, Andrew S. Artz, Richard E. Champlin, Stella M. Davies, Madan Jagasia, Nancy A. Kernan, Fausto Loberiza Jr, Robert J. Soiffer, Mary Eapen
We thank all respondents for taking the time to complete the survey and CIBMTR for facilitating survey distribution.
published online ahead of print at www.jco.org on March 31, 2008. Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Wennberg J, Gittelsohn A: Small area variations in health care delivery. Science 182:1102-1108, 1973 2. Grytten J, Sorensen R: Practice variation and physician-specific effects. J Health Econ 22:403-418, 2003[CrossRef][Medline] 3. Kravitz RL, Greenfield S: Variations in resource utilization among medical specialties and systems of care. Annu Rev Public Health 16:431-445, 1995[CrossRef][Medline] 4. Silberman G, Crosse MG, Peterson EA, et al: Availability and appropriateness of allogeneic bone marrow transplantation for chronic myeloid leukemia in 10 countries. N Engl J Med 331:1063-1067, 1994 5. Gratwohl A, Brand R, Apperley J, et al: Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: Transplant activity, long-term data and current results: An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 91:513-521, 2006 6. Gratwohl A, Baldomero H, Schwendener A, et al: Hematopoietic stem cell transplants for chronic myeloid leukemia in Europe–impact of cost considerations. Leukemia 21:383-386, 2007[CrossRef][Medline] 7. Gratwohl A, Baldomero H, Frauendorfer K, et al: Results of the EBMT activity survey 2005 on haematopoietic stem cell transplantation: Focus on increasing use of unrelated donors. Bone Marrow Transplant 39:71-87, 2007[CrossRef][Medline] 8. Windrum P, Morris TC, Drake MB, et al: Variation in dimethyl sulfoxide use in stem cell transplantation: A survey of EBMT centres. Bone Marrow Transplant 36:601-603, 2005[CrossRef][Medline] 9. Ruutu T, Niederwieser D, Gratwohl A, et al: A survey of the prophylaxis and treatment of acute GVHD in Europe: A report of the European Group for Blood and Marrow, Transplantation (EBMT): Chronic Leukaemia Working Party of the EBMT. Bone Marrow Transplant 19:759-764, 1997[CrossRef][Medline] 10. Hsu B, May R, Carrum G, et al: Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: An international practice survey. Bone Marrow Transplant 28:945-950, 2001[CrossRef][Medline] 11. Trifilio S, Verma A, Mehta J: Antimicrobial prophylaxis in hematopoietic stem cell transplant recipients: Heterogeneity of current clinical practice. Bone Marrow Transplant 33:735-739, 2004[CrossRef][Medline] 12. Lee SJ, Vogelsang G, Gilman A, et al: A survey of diagnosis, management, and grading of chronic GVHD. Biol Blood Marrow Transplant 8:32-39, 2002[CrossRef][Medline] 13. Ruutu T, Hermans J, van Biezen A, et al: How should corticosteroids be used in the treatment of acute GVHD? EBMT Chronic Leukemia Working Party: European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 22:614-615, 1998[CrossRef][Medline] 14. Parsons SK, Hoorntje LE, Levine KJ, et al: Balancing efficacy with cost: Antiemetic control in the pediatric stem cell transplant (SCT) population. Bone Marrow Transplant 25:553-557, 2000[CrossRef][Medline] 15. Lafata JE, Simpkins J, Schultz L, et al: Routine surveillance care after cancer treatment with curative intent. Med Care 43:592-599, 2005[CrossRef][Medline] 16. Lindenauer PK, Pekow P, Gao S, et al: Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 144:894-903, 2006 17. Choy H, Shyr Y, Cmelak AJ, et al: Patterns of practice survey for nonsmall cell lung carcinoma in the U.S. Cancer 88:1336-1346, 2000[CrossRef] 18. Ng AK, Li S, Neuberg D, et al: Factors influencing treatment recommendations in early-stage Hodgkin's disease: A survey of physicians. Ann Oncol 15:261-269, 2004 19. Taghian A, Jagsi R, Makris A, et al: Results of a survey regarding irradiation of internal mammary chain in patients with breast cancer: Practice is culture driven rather than evidence based. Int J Radiat Oncol Biol Phys 60:706-714, 2004[CrossRef][Medline] 20. Katz SJ, Lantz PM, Janz NK, et al: Surgeon perspectives about local therapy for breast carcinoma. Cancer 104:1854-1861, 2005[CrossRef][Medline] 21. United Nations World Macro regions and components 2007. http://www.un.org/depts/dhl/maplib/worldregions/htm 22. Schrezenmeier H, Passweg JR, Marsh JC, et al: Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood 110:1397-1400, 2007 23. Champlin RE, Perez WS, Passweg JR, et al: Bone marrow transplantation for severe aplastic anemia: A randomized controlled study of conditioning regimens. Blood 109:4582-4585, 2007 24. Bruno B, Rotta M, Patriarca F, et al: A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 356:1110-1120, 2007 25. Creutzig U, Reinhardt D: Current controversies: Which patients with acute myeloid leukaemia should receive a bone marrow transplantation? A European view. Br J Haematol 118:365-377, 2002[CrossRef][Medline] 26. Chen AR, Alonzo TA, Woods WG, et al: Current controversies: Which patients with acute myeloid leukaemia should receive a bone marrow transplantation? An American view. Br J Haematol 118:378-384, 2002[CrossRef][Medline] 27. Hasle H, Arico M, Basso G, et al: Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7: European Working Group on MDS in Childhood (EWOG-MDS). Leukemia 13:376-385, 1999[CrossRef][Medline] 28. Woods WG, Barnard DR, Alonzo TA, et al: Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: A report from the Children's Cancer Group. J Clin Oncol 20:434-440, 2002 29. Van Lint MT, Uderzo C, Locasciulli A, et al: Early treatment of acute graft-versus-host disease with high- or low- dose 6-methylprednisolone: A multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. Blood 92:2288-2293, 1998 30. Asch DA, Jedrziewski MK, Christakis NA: Response rates to mail surveys published in medical journals. J Clin Epidemiol 50:1129-1136, 1997[CrossRef][Medline] 31. Wusthoff CJ, McMillan A, Ablin AR: Differences in pediatric oncologists' estimates of curability and treatment recommendations for patients with advanced cancer. Pediatr Blood Cancer 44:174-181, 2005[CrossRef][Medline] 32. Charles CA, Yee VS, Dusza SW, et al: Variation in the diagnosis, treatment, and management of melanoma in situ: A survey of US dermatologists. Arch Dermatol 141:723-729, 2005 33. Peabody JW, Luck J, Glassman P, et al: Comparison of vignettes, standardized patients, and chart abstraction: A prospective validation study of 3 methods for measuring quality. JAMA 283:1715-1722, 2000 34. Veloski J, Tai S, Evans AS, et al: Clinical vignette-based surveys: A tool for assessing physician practice variation. Am J Med Qual 20:151-157, 2005 35. Eagle KA, Goodman SG, Avezum A, et al: Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: Findings from the Global Registry of Acute Coronary Events (GRACE). Lancet 359:373-377, 2002[CrossRef][Medline] 36. Hawley ST, Hofer TP, Janz NK, et al: Correlates of between-surgeon variation in breast cancer treatments. Med Care 44:609-616, 2006[CrossRef][Medline] 37. Alexander KP, Newby LK, Bhapkar MV, et al: International variation in invasive care of the elderly with acute coronary syndromes. Eur Heart J 27:1558-1564, 2006 Submitted October 22, 2007; accepted December 20, 2007.
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
2, Fisher's exact, Mantel-Haenszel 
