Clinicians' adherence versus non adherence to practice guidelines in the management of patients with sarcoma: a cost-effectiveness assessment in two European regions
- Lionel Perrier1Email author,
- Alessandra Buja2,
- Giuseppe Mastrangelo3,
- Antonella Vecchiato4,
- Paolo Sandonà5,
- Françoise Ducimetière6,
- Jean-Yves Blay7,
- François Noël Gilly8,
- Carole Siani9,
- Pierre Biron10,
- Dominique Ranchère-Vince11,
- Anne-Valérie Decouvelaere12,
- Philippe Thiesse13,
- Christophe Bergeron14,
- Angelo Paolo Dei Tos15,
- Jean-Michel Coindre16,
- Carlo Riccardo Rossi17 and
- Isabelle Ray-Coquard18
© Perrier et al; licensee BioMed Central Ltd. 2012
Received: 28 July 2011
Accepted: 28 March 2012
Published: 28 March 2012
Although the management of sarcoma is improving, non adherence to clinical practice guidelines (CPGs) remains high, mainly because of the low incidence of the disease and the variety of histological subtypes. Since little is known about the health economics of sarcoma, we undertook a cost-effectiveness analysis (within the CONnective TIssue CAncer NETwork, CONTICANET) comparing costs and outcomes when clinicians adhered to CPGs and when they did not.
Patients studied had a histological diagnosis of sarcoma, were older than 15 years, and had been treated in the Rhône-Alpes region of France (in 2005/2006) or in the Veneto region of Italy (in 2007). Data collected retrospectively for the three years after diagnosis were used to determine relapse free survival and health costs (adopting the hospital's perspective and a microcosting approach). All costs were expressed in euros (€) at their 2009 value. A 4% annual discount rate was applied to both costs and effects. The incremental cost-effectiveness ratio (ICER) was expressed as cost per relapse-free year gained when management was compliant with CPGs compared with when it was not. To capture uncertainty surrounding ICER, a probabilistic sensitivity analysis was performed based on a non-parametric bootstrap method.
A total of 219 patients were included in the study. Compliance with CPGs was observed for 118 patients (54%). Average total costs reached 23,571 euros when treatment was in accordance with CPGs and 27,313 euros when it was not. In relation to relapse-free survival, compliance with CPGs strictly dominates non compliance, i.e. it is both less costly and more effective. Taking uncertainty into account, the probability that compliance with CPGs still strictly dominates was 75%.
Our findings should encourage physicians to increase their compliance with CPGs and healthcare administrators to invest in the implementation of CPGs in the management of sarcoma.
KeywordsSarcoma Cancer Clinical practice guidelines Adherence Compliance Cost-effectiveness
Sarcomas are rare tumours (accounting for only 1-2% of all cancers) originating from connective tissue, skin, retroperitoneum, bone and viscera . The rarity of the disease, along with the variety of histological types and locations and the heterogeneity of prognostic factors associated with local or distant spread, mean that physicians have only limited personal experience of managing the disease. Furthermore, outside centres of excellence, there is little graduate or post-graduate medical training in its optimum management. To improve the diagnosis and prognosis of sarcoma, the European Commission funded the Connective Tissue Cancer Network (CONTICANET) aimed at increasing the standardization of diagnostic and therapeutic procedures.
In order to reduce inappropriate medical procedures, Clinical Practice Guidelines (CPGs) were developed by the Fédération Nationale des Centres de Lutte contre le Cancer (the French Federation of Comprehensive Cancer Centres)  and by the Italian National Research Council . France and Italy reached a consensus in their CPGs relating to all phases of sarcoma management (initial examination and diagnosis, histopathological report, surgery, chemotherapy, and radiation therapy) except surveillance after therapy (see Annexe 1).
The impact of adherence to CPGs has received some research attention [4–10], even in the management of rare cancers [11–14]. However, little is known about the financial impact of clinicians' adherence to CPGs in general, and the impact of adherence on outcomes and costs of care has only rarely been simultaneously considered . Such assessments are of particular value in the current period of budgetary constraint, which prevents the achievement of improved cancer outcomes through increased health expenditure [16, 17].
We therefore assessed the cost-effectiveness of compliance with CPGs in sarcoma management by investigating the relationship between health outcome and resource consumption in patients treated in the regions of the Rhône-Alpes in France and Veneto in Italy.
Attrition of the study population
Care outside the region
Data not available@
Hospital records were used to obtain data on the characteristics of patients (age, sex, comorbidities) and their sarcomas (visceral or soft tissue; superficial or deep tumour); localization in lower or upper limb, head-neck or trunk; histological subtype; major tumour diameter at imaging and surgery; and grade). Data were also obtained on resources utilization (using a micro-costing approach) at diagnosis and during surgery (primary and wide surgical resection), chemotherapy (drugs administered in hospital or outpatient facilities) and radiotherapy (sessions in hospital or outpatient facilities). We also obtained data covering relapse or metastasis during follow up, along with any subsequent need for surgical interventions, chemotherapy and/or radiotherapy. Information was collected on number of days of hospitalization, use of pathology resources such as micro-biopsy and cytology), use of imaging, and supportive treatments such as antibiotics. The date of relapse was used to calculate relapse free survival from diagnosis.
Physicians independent of the study (two from the Léon Bérard Cancer Centre and two from the University of Padua) assessed whether or not there had been compliance with CPGs in each management phase covered by such guidelines. Overall management was considered to have been compliant only when CPGs had been followed at all stages of diagnosis, treatment, and follow-up.
Costs and indicators of effectiveness
Main unit costs and prices
Unit costs and prices
Sources of information
Hospitalization (per day)
Radiotherapy (per session)
Chemo-therapy(per milligram of drugs)
Transfusion (per pack)
Red blood cell
Magnetic Resonance Imaging
Chi-square or t-tests were used, according to the type of data, to compare compliant (CPG+) and non compliant (CPG-) groups. Analysis of variance (ANOVA) was used to explore the costs of overall management according to histological subtype. Univariate survival analyses were performed using the Kaplan-Meier method and the log-rank test. The log-rank test was used to assess the effect of compliance with CPGs on survival after adjusting for confounding variables.
The incremental cost-effectiveness ratio (ICER), expressing the incremental cost per additional relapse-free year gained.
The outer ellipse defines the confidence region for the mean cost difference and mean effect difference pair at the 95% level and the inner ellipse at the 50% level. The outer ellipse is equivalent to an acceptability region for an inference test at 5% significance level whose null hypothesis is the mean cost difference and mean effect difference pair being equal to (0, 0). Consequently, if the origin of the cost-effectiveness plane does not belong to the confidence ellipse, then both the management of patients with sarcoma (adherence versus non adherence to CPGs) are significantly different regarding costs and effects. For more robustness in the results, in addition to confidence ellipses, uncertainty around the ICER was taken into account by examining probabilities that it belonged to each of the quadrants of the cost-effectiveness plane.
Calculations were performed using STATA 11 and Gauss software version 9.0.
Clinical characteristics of patients by group: Mean ± SD or number of patients and (%)
All patients n = 219
CPG (+) n = 118
CPG (-) n = 101
60.4 ± 15.0
60.1 ± 15.3
60.7 ± 14.8
low (grade I)
intermediate (grade II)
high (grade III)
Tumour size in mm
94.6 ± 80.6
96.8 ± 91.4
91.9 ± 66.3
Relapse free survival (years)
Average costs for each phase of sarcoma management by group (in €, 2009)
Phases of treatment
Incremental cost-effectiveness ratio (ICER) for clinicians' adherence versus non adherence to clinical practice guidelines (CPGs)
Mean cost per patient(€, 2009)
Mean Incremental Cost[](€, 2009)
Mean effectiveness per patient(Relapse-free survival, years)
Mean Incremental Effectiveness[](Relapse-free survival, years)
ICER(€ per relapse-free year gained)[]
Overall management CPG (+)
Overall management CPG (-)
A weakness of the present study is that its retrospective nature did not allow assessment of outcome in cost per Quality Adjusted Life Year (QALY), as recommended by the National Institute for Health and Clinical Excellence (NICE) [24, 25]. Notwithstanding this, freedom from relapse undoubtedly contributes to quality of life in cancer patients.
Another weakness was the lack of information on potentially confounding variables such as the initial performance status of the patient, the cumulative volume for the surgeon and the hospital, the type of provider (academic cancer centre, non academic cancer centre, non academic non cancer centre) [26–28] that could not be controlled for in the statistical analysis. Any resulting bias, however, would have tended to cause an underestimation rather than an overestimation of the true effect of compliance, since in the CPG + group the costs of diagnosis were higher (Table 4) despite a lower grade of tumours (Table 3).
Interestingly, the higher overall cost involved in diagnosing patients according to CPGs was accounted for almost entirely by increased hospitalisation (rather than by greater use of imaging or biopsy or external consultations) (Table 4). The average cost of hospitalization was €4,097 in CPG + and €2,317 in CPG- groups. The difference corresponds to 2.3 additional days of hospital stay at the prevailing daily cost of €760 per day (Table 2). Adherence to CPGs requires that decisions be made within a multidisciplinary committee, and it is likely that patients' hospitalization was prolonged in order to schedule the multidisciplinary meeting needed to reach a consensus on treatment.
A greater adherence to CPGs during diagnosis appears to decrease all subsequent costs, notably those of surgery and chemotherapy, probably by reducing the need for surgical re-intervention or more intense use of antineoplastic drugs (Table 4). Surgery and chemotherapy were the main factors driving the cost of initial treatment, representing about 66% of the overall cost in the CPG + group ((7,397 + 5,164)/19,175) and 76% ((9,075 + 7,207)/21,502) in the CPG- group.
In contrast to other studies that have shown it may be cheaper in the short term to deviate from CPGs , the present study found that compliance with CPGs strictly dominates for relapse-free survival, meaning that management of sarcoma according to CPGs is less costly and more effective. This evidence should encourage health providers to promote adherence to guidelines since adopting this approach achieves a better quality of care and is a more efficient allocation of resources. It should also encourage compliance among physicians, some of whom perceive CPGs as limiting their freedom to make diagnostic and therapeutic decisions.
Compliance with CPGs in sarcoma management has increased since 2001. A retrospective study of the medical records of sarcoma patients in the University Hospital of Lyon and the Cancer Centre Léon Bérard found that between 1999 and 2001 initial clinical management had been consistent with the CPG in only 32% of cases . In this study, the compliance rate reached 54%. Compliance with guidelines was greater for chemotherapy than for other aspects of sarcoma management since detailed protocols are more common than in diagnosis, surgery, radiotherapy or follow up. Compliance with CPGs was also more frequent for low-grade than for high-grade sarcomas (p = 0.01); and it has been suggested that physicians are less likely to adhere to CPGs if they believe that compliance will not improve outcome . Compliance was also better for GIST than for other histologies, probably because imatinib and related drugs have led to a remarkable improvement in management on which there is global consensus .
The present findings should encourage physicians' efforts to increase their compliance with CPGs and encourage healthcare administrators to invest in implementing CPGs in the management of sarcoma.
Analysis of variance
Clinical practice guidelines
- CPG +:
Clinicians' adherent to practice guidelines
Clinicians' non adherent to practice guidelines
Connective tissues cancers network
Gastro Intestinal Stromal Tumours
French National Authority for Health (Haute Autorité de Santé)
Incremental cost-effectiveness ratio
National Institute for Health and Clinical Excellence
Not otherwise specified
Quality adjusted life year
The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement n°278742, the Network of Excellence CONTICANET (contract code: FP-018806), Canceropole Lyon Auvergne Rhone-Alpes CLARA (contract code: 2010 ProCan IV-2ERPCS), and Merck Serono. The authors thank for their collaboration Eurosarc, CONTICANET, CLARA and Merck Serono for financial support, as well as Giuseppe Zamengo (Direzione Regionale Risorse Socio Sanitarie, Servizio Sistema Informativo Socio Sanitario e Tecnologie Informatiche, Regione Veneto), Pr Cyrille Colin (Direction de l'information hospitalière, Hospices Civils de Lyon), Dr Frédéric Gomez (Direction de l'information hospitalière, Centre Léon Bérard), Mr Nicolas Caquot (Direction administrative et financière, Centre Léon Bérard), and Mrs Marine Genton (Master student, Université Lumière Lyon 2). The authors would like to thank the referees for their insightful comments and suggestions. Rob Stepney, medical writer, Charlbury, UK, assisted with the final editing of the manuscript.
Appendix A. Annexe 1. Main CPG criteria for each sequence of initial sarcoma treatment
Main Criteria for diagnosis: Clinical size and depth of the tumour mass must be recorded; Computed Tomography (CT) is required for abdominal localizations, or Magnetic Resonance Imaging (MRI) for limb localizations; Chest radiograph or CT scan is required to identify metastases; Initial biopsy (incisional or needle), preferably by the surgeon in charge of future surgical procedures, is required for bone and soft tissue sarcomas, with the exception of small tumours (< 3 cm) for which excisional biopsy is considered appropriate.
Main Criteria for surgery: Whenever possible, primary surgery should involve a wide excision with 1-2 cm margins. For high-grade, large (> 3 cm) or deep-seated tumours, surgery alone is acceptable only in case of amputation or compartmental resection with negative histological margins (R0). Wide excision alone, with no adjuvant treatment, is acceptable only for superficial, small (< 3 cm) and low-grade lesions. Histologically positive margins (R1) or incomplete excision (R2) have to be considered inadequate, and should be followed by further appropriate treatment.
Main criteria for chemotherapy: For non-readily operable sarcomas, primary chemotherapy or radiation therapy can be an option. For readily operable sarcomas, neo-adjuvant chemotherapy should be performed only as part of a clinical research protocol. In the adjuvant setting, systemic chemotherapy should be performed only within the context of a prospective clinical trial. Adjuvant chemotherapy can be performed for patients with histologically positive margins after wide surgical excision.
Main criteria for radiation therapy: Association of wide surgical excision and adjuvant radiation therapy should be considered the standard treatment. The absence of adjuvant radiotherapy is acceptable for superficial, small (< 3 cm) and low-grade tumours, and for limb sarcomas when amputation is performed. For non-operable sarcomas, primary radiation therapy could be an option. The optimal treatment strategy involves a 50 Gy delivered dose with an additional boost of 10 Gy in case of microscopic residual tumour (R1), with a target volume encompassing the tumour bed and surgical scars, including draining orifices, with adapted security margins. Moreover, the interval from surgery to radiation therapy must not be longer than 8 weeks.
- Mastrangelo G, Fadda E, Cegolon L, Montesco MC, Ray-Coquard I, Buja A, Fedeli U, Frasson A, Spolaore P, Rossi CR: A European project on incidence, treatment, and outcome of sarcoma. BMC Publ Health. 2010, 10: 188-10.1186/1471-2458-10-188.View ArticleGoogle Scholar
- FNCLCC: Standards, Options et Recommandations pour la prise en charge des patients adultes atteints de sarcome des tissus mous, de sarcome utérin ou de tumeur stromale gastro-intestinale. 1995, [http://www.sor-cancer.fr/]Google Scholar
- Italian National Research Council in Italy. [http://progettooncologia.cnr.it/bridge/attivita-direzione.html]
- Mercuri M, Gafni A: Medical practice variations: what the literature tells us (or does not) about what are warranted and unwarranted variations. J Eval Clin Pract. 2011, 17: 671-677. 10.1111/j.1365-2753.2011.01689.x.View ArticlePubMedGoogle Scholar
- Ray-Coquard I, Philip T, Ray-Coquard I, Philip T, De LG, Froger X, Suchaud JP, Voloch A, Mathieu-Daudé H, Fervers B, Farsi F, Browman GP, Chauvin F: A controlled "before-after" study: impact of a clinical guidelines programme and regional cancer network organization on medical practice. Br J Cancer. 2002, 86: 313-321. 10.1038/sj.bjc.6600057.View ArticlePubMedPubMed CentralGoogle Scholar
- Ray-Coquard I, Philip T, De LG, Froger X, Suchaud JP, Voloch A, Mathieu-Daudé H, Lurkin A, Farsi F, Bertrand P, Chauvin F: Persistence of medical change at implementation of clinical guidelines on medical practice: a controlled study in a cancer network. J Clin Oncol. 2005, 23: 4414-4423. 10.1200/JCO.2005.01.040.View ArticlePubMedGoogle Scholar
- Kaegi L: Policy, management, and clinical practice implications get priority attention of health services researchers. QRB Qual Rev Bull. 1991, 17: 297-304.PubMedGoogle Scholar
- Audet AM, Greenfield S, Field M: Medical practice guidelines: current activities and future directions. Ann Intern Med. 1990, 113: 709-714.View ArticlePubMedGoogle Scholar
- Ray-Coquard I, Philip T, Lehmann M, Fervers B, Farsi F, Chauvin F: Impact of a clinical guidelines program for breast and colon cancer in a French cancer center. JAMA. 1997, 278: 1591-1595. 10.1001/jama.1997.03550190055044.View ArticlePubMedGoogle Scholar
- Osarogiagbon RU, Phelps G, McFarlane J, Bankole O: Causes and consequences of deviation from multidisciplinary care in thoracic oncology. J Thorac Oncol. 2011, 6: 510-516. 10.1097/JTO.0b013e31820b88a7.View ArticlePubMedGoogle Scholar
- Grimer R, Judson I, Peake D, Seddon B: Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010, 201: 506182.Google Scholar
- Ray-Coquard I, Thiesse P, Ranchere-Vince D, Chauvin F, Bobin JY, Sunyach MP, Carret JP, Mongodin B, Marec-Bérard P, Philip T, Blay JY: Conformity to clinical practice guidelines, multidisciplinary management and outcome of treatment for soft tissue sarcomas. Ann Oncol. 2004, 15: 307-315. 10.1093/annonc/mdh058.View ArticlePubMedGoogle Scholar
- Jansen-Landheer ML, Krijnen P, Oostindiër MJ, Kloosterman-Boele WM, Noordijk EM, Nooij MA, Steup WH, Taminiau AH, Vree R, Hogendoorn PC, Tollenaar RA, Gelderblom H: Improved diagnosis and treatment of soft tissue sarcoma patients after implementation of national guidelines: a population-based study. Eur J Surg Oncol. 2009, 35: 1326-1332. 10.1016/j.ejso.2009.05.002.View ArticlePubMedGoogle Scholar
- Cutts S, Andrea F, Piana R, Haywood R: The management of soft tissue sarcomas. Surgeon. 2012, 10: 25-32. 10.1016/j.surge.2011.09.006.View ArticlePubMedGoogle Scholar
- Fritz JM, Cleland JA, Brennan GP: Does adherence to the guideline recommendation for active treatments improve the quality of care for patients with acute low back pain delivered by physical therapists?. Med Care. 2007, 45: 973-980. 10.1097/MLR.0b013e318070c6cd.View ArticlePubMedGoogle Scholar
- Lichtenberg F: The expanding pharmaceutical arsenal in the war on cancer. NBER. 2004, Working Paper n°10328Google Scholar
- Martin S, Rice N, Smith PC: Does health care spending improve health outcomes? Evidence from English programme budgeting data. J Health Econ. 2008, 27: 826-842. 10.1016/j.jhealeco.2007.12.002.View ArticlePubMedGoogle Scholar
- Drummond MF, Sculpher MJ, Torrance GW, O'Brien BJ, Stoddart GL: Methods for the economics evaluation of health care programme. 2005, New-York: Oxford University Press, 3Google Scholar
- Regione del Veneto, Nomenclatore Tariffario Prestazioni Specialistiche Ambulatoriali. [http://www.regione.veneto.it/NR/rdonlyres/180C6757-EB04-4AB2-8404-681093D15379/0/ALLEGATO_1_vigenti_delibera.pdf]
- Classification commune des actes médicaux.[http://www.ameli.fr/accueil-de-la-ccam/trouver-un-acte/consultation-par-chapitre.php?add=16.2.5]
- Arrêté du 2 janvier 2008 relatif au tarif de cession des produits sanguins labiles. Journal officiel de la République française. 10 février 2008, N°35 [http://www.journal-officiel.gouv.fr/frameset.html]
- Haute autorité de santé (HAS): Choix méthodologiques pour l'évaluation économique à la HAS. [http://www.has-sante.fr/portail/upload/docs/application/pdf/2011-11/guide_methodo_vf.pdf]
- Claxton K, Sculpher M, McCabe C, Briggs A, Akehurst R, Buxton M, Brazier J, O'Hagan T: Probabilistic sensitivity analysis for NICE technology assessment: not an optional extra. Health Econ. 2005, 14: 339-347. 10.1002/hec.985.View ArticlePubMedGoogle Scholar
- McCabe C, Claxton K, Culyer AJ: The NICE cost-effectiveness threshold: what it is and what that means. PharmacoEconomics. 2008, 26: 733-744. 10.2165/00019053-200826090-00004.View ArticlePubMedGoogle Scholar
- National Institute for Health and Clinical Excellence. [http://www.nice.org.uk/media/68D/29/The_guidelines_manual_2009_-_Chapter_7_Assessing_cost_effectiveness.pdf]
- Salloum RG, Smith TJ, Jensen GA, Lafata JE: Factors associated with adherence to chemotherapy guidelines in patients with non-small cell lung cancer. Lung Cancer. 2011Google Scholar
- Chamie K, Saigal CS, Lai J, Hanley JM, Setodji CM, Konety BR: Litwin MS; Urologic Diseases in America Project: Compliance with guidelines for patients with bladder cancer: Variation in the delivery of care. Cancer. 2011, 117: 5392-5401. 10.1002/cncr.26198.View ArticlePubMedPubMed CentralGoogle Scholar
- Lebeau M, Mathoulin-Pélissier S, Bellera C, Tunon-de-Lara C, Daban A, Lipinski F, Jaubert D, Ingrand P: Migeot V; REPERES Group: Breast cancer care compared with clinical Guidelines: an observational study in France. BMC Publ Health. 2011, 11: 45-10.1186/1471-2458-11-45.View ArticleGoogle Scholar
- Ozminkowski RJ, Wang S, Marder WD, Azzolini J: Short-run associations between medical care expenditures and adherence to clinical practice guideline-based measures for diabetes. Value Health. 2000, 3 (Suppl 1): 29-38.View ArticlePubMedGoogle Scholar
- Cabana MD, Rand CS, Powe NR, Wu AW, Wilson MH, Abboud PA, Rubin HR: Why don't physicians follow clinical practice guidelines? A framework for improvement. JAMA. 1999, 282: 1458-1465. 10.1001/jama.282.15.1458.View ArticlePubMedGoogle Scholar
- Reichardt P, Blay JY, Mehren M: Towards global consensus in the treatment of gastrointestinal stromal tumor. Expert Rev Anticancer Ther. 2010, 10: 221-232. 10.1586/era.09.171.View ArticlePubMedPubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/82/prepub
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