Early health economic modelling of single‐stage cartilage repair. Guiding implementation of technologies in regenerative medicine

Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair – such as autologous chondrocyte implantation (ACI) – plus increasing healthcare costs, and market competition, are forcing a shift in focus from two‐stage to single‐stage interventions that are more cost‐effective. Early health economic models are expected to provide essential insight in the parameters driving the cost‐effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost‐effectiveness ratio (ICER) of a new investigator‐driven single‐stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost‐effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of €30 000/QALY. One‐way sensitivity analysis was performed to identify those parameters that drive the cost‐effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be €11 797, €29 741 and €6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from €147 513/QALY to €28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost‐effective treatment option for smaller defects, a single‐stage tissue engineering procedure can replace ACI to improve the cost‐effectiveness for treating larger defects, especially if clinical non‐inferiority can be achieved. Copyright © 2016 John Wiley & Sons, Ltd.

[1]  K. Otani,et al.  Healthcare Cost and Predictive Factors: High- and Low-Utilization Model Development , 2009, Health marketing quarterly.

[2]  Eric M. Samuelson,et al.  Cost-Effectiveness Analysis of Autologous Chondrocyte Implantation , 2012, The American journal of sports medicine.

[3]  Wouter J A Dhert,et al.  Single-Stage Cell-Based Cartilage Regeneration Using a Combination of Chondrons and Mesenchymal Stromal Cells , 2013, The American journal of sports medicine.

[4]  C. Ohlsson,et al.  Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. , 1994, The New England journal of medicine.

[5]  D. Kelly,et al.  Combining freshly isolated chondroprogenitor cells from the infrapatellar fat pad with a growth factor delivery hydrogel as a putative single stage therapy for articular cartilage repair. , 2014, Tissue engineering. Part A.

[6]  Brian J. Cole,et al.  Autologous Chondrocyte Implantation , 2001 .

[7]  R. Marx,et al.  Cost-Effectiveness Analysis of Early Reconstruction Versus Rehabilitation and Delayed Reconstruction for Anterior Cruciate Ligament Tears , 2014, The American journal of sports medicine.

[8]  E. Roos,et al.  The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis , 2003, Health and quality of life outcomes.

[9]  S. Fuchs-Winkelmann,et al.  Cell-free collagen type I matrix for repair of cartilage defects—clinical and magnetic resonance imaging results , 2012, Knee Surgery, Sports Traumatology, Arthroscopy.

[10]  B. Min,et al.  Histomorphochemical comparison of microfracture as a first‐line and a salvage procedure: Is microfracture still a viable option for knee cartilage repair in a salvage situation? , 2014, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  T. Ackland,et al.  A Randomized Trial Comparing Accelerated and Traditional Approaches to Postoperative Weightbearing Rehabilitation After Matrix-Induced Autologous Chondrocyte Implantation , 2012, The American journal of sports medicine.

[12]  D. Saris,et al.  Functional articular cartilage repair: here, near, or is the best approach not yet clear? , 2013, Nature Reviews Rheumatology.

[13]  J A Skinner,et al.  Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. , 2012, The Journal of bone and joint surgery. British volume.

[14]  Grazyna Adamiak,et al.  Methods for the economic evaluation of health care programmes, 3rd ed , 2006 .

[15]  F. Luyten,et al.  Cartilage Defects of the Knee : Early Treatment Matters Five-Year Outcome of Characterized Chondrocyte Implantation Versus Microfracture for Symptomatic , 2011 .

[16]  Bert R. Mandelbaum,et al.  Clinical Efficacy of the Microfracture Technique for Articular Cartilage Repair in the Knee , 2009, The American journal of sports medicine.

[17]  B. Morrey A Prospective Multicenter Study on the Outcome of Type I Collagen Hydrogel–Based Autologous Chondrocyte Implantation (CaReS) for the Repair of Articular Cartilage Defects in the Knee , 2012 .

[18]  Maarten J. IJzerman,et al.  Early assessment of medical technologies to inform product development and market access , 2011, Applied health economics and health policy.

[19]  Hong-chul Lim,et al.  Current Treatments of Isolated Articular Cartilage Lesions of the Knee Achieve Similar Outcomes , 2012, Clinical orthopaedics and related research.

[20]  S. Anders,et al.  Send Orders of Reprints at Reprints@benthamscience.net a Randomized, Controlled Trial Comparing Autologous Matrix-induced Chondrogenesis (amic ® ) to Microfracture: Analysis of 1-and 2-year Follow-up Data of 2 Centers , 2022 .

[21]  T. Ackland,et al.  Clinical and Magnetic Resonance Imaging–Based Outcomes to 5 Years After Matrix-Induced Autologous Chondrocyte Implantation to Address Articular Cartilage Defects in the Knee , 2011, The American journal of sports medicine.

[22]  Joshua D. Harris,et al.  Treatment of Cartilage Defects of the Knee: Expanding on the Existing Algorithm , 2014, Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine.

[23]  Benedict U. Nwachukwu,et al.  Cost-Effectiveness Analyses in Orthopaedic Sports Medicine , 2015, The American journal of sports medicine.

[24]  J. Frappier Economic Evaluation Of Bst-Cargel As An Adjunct To Microfracture Versus Microfracture Alone In Knee Cartilage Surgery , 2015 .

[25]  Haris S. Vasiliadis,et al.  Autologous Chondrocyte Implantation , 2010, The American journal of sports medicine.

[26]  D. Parker,et al.  Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: a systematic review. , 2015, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[27]  M. Delcogliano,et al.  Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee , 2013, Knee Surgery, Sports Traumatology, Arthroscopy.

[28]  V. Vécsei,et al.  Do meta-analyses reveal time-dependent differences between the clinical outcomes achieved by microfracture and autologous chondrocyte implantation in the treatment of cartilage defects of the knee? , 2013, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[29]  Xing Zhao,et al.  Concise Review: Unraveling Stem Cell Cocultures in Regenerative Medicine: Which Cell Interactions Steer Cartilage Regeneration and How? , 2014, Stem cells translational medicine.

[30]  D. Saris,et al.  Validation of the Knee Injury and Osteoarthritis Outcome Score (KOOS) for the treatment of focal cartilage lesions. , 2009, Osteoarthritis and cartilage.

[31]  B. Penninx,et al.  A Randomized Controlled Trial of a Tailored Primary Care Program to Reverse Excessive Alcohol Consumption , 2012, The Journal of the American Board of Family Medicine.

[32]  David Stelzeneder,et al.  Autologous collagen-induced chondrogenesis: single-stage arthroscopic cartilage repair technique. , 2013, Orthopedics.

[33]  David Morganstein,et al.  Cost of lost productive work time among US workers with depression. , 2003, JAMA.

[34]  D. Saris,et al.  Follow-up of a Prospective Randomized Trial Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture : Two-Year , 2014 .

[35]  Maximilian Rudert,et al.  A Prospective Multicenter Study on the Outcome of Type I Collagen Hydrogel–Based Autologous Chondrocyte Implantation (CaReS) for the Repair of Articular Cartilage Defects in the Knee , 2011, The American journal of sports medicine.

[36]  Maurilio Marcacci,et al.  Scaffold-based repair for cartilage healing: a systematic review and technical note. , 2013, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[37]  S. Wilson Methods for the economic evaluation of health care programmes , 1987 .

[38]  R. Gudas,et al.  Ten-Year Follow-up of a Prospective, Randomized Clinical Study of Mosaic Osteochondral Autologous Transplantation Versus Microfracture for the Treatment of Osteochondral Defects in the Knee Joint of Athletes , 2012, The American journal of sports medicine.

[39]  G. Bentley,et al.  The role of the Short Form 36 Health Survey in autologous chondrocyte implantation. , 2005, The Knee.

[40]  J. Hart,et al.  Preliminary results of a novel single-stage cartilage restoration technique: particulated juvenile articular cartilage allograft for chondral defects of the patella. , 2013, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[41]  D. Flanigan,et al.  Failures, re-operations, and complications after autologous chondrocyte implantation--a systematic review. , 2011, Osteoarthritis and cartilage.

[42]  D. Saris,et al.  Joint homeostasis. The discrepancy between old and fresh defects in cartilage repair. , 2003, The Journal of bone and joint surgery. British volume.

[43]  S. Concaro,et al.  Strategies for patient profiling in articular cartilage repair of the knee: a prospective cohort of patients treated by one experienced cartilage surgeon , 2012, Knee Surgery, Sports Traumatology, Arthroscopy.

[44]  A. Gross,et al.  Outcomes of osteochondral allograft transplantation in the knee. , 2013, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[45]  Joshua D. Harris,et al.  Trends in the surgical treatment of articular cartilage lesions in the United States: an analysis of a large private-payer database over a period of 8 years. , 2014, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[46]  David W. Levine,et al.  Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture , 2014, The American journal of sports medicine.

[47]  N. Markowitz,et al.  A ten-year follow-up , 1979 .

[48]  M. Shive,et al.  Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. , 2013, The Journal of bone and joint surgery. American volume.

[49]  P. J. Chilton,et al.  Evaluation of a predevelopment service delivery intervention: an application to improve clinical handovers , 2012, BMJ quality & safety.

[50]  D. Saris,et al.  Treatment Selection in Articular Cartilage Lesions of the Knee , 2009, The American journal of sports medicine.

[51]  M A Koopmanschap,et al.  The friction cost method for measuring indirect costs of disease. , 1995, Journal of health economics.

[52]  Peter Wood,et al.  Cost‐effectiveness analysis at the development phase of a potential health technology: examples based on tissue engineering of bladder and urethra , 2007, Journal of tissue engineering and regenerative medicine.

[53]  N. Südkamp,et al.  Autologous Chondrocyte Implantation for Treatment of Cartilage Defects of the Knee , 2012, The American journal of sports medicine.

[54]  Johan Vanlauwe,et al.  The Cost Utility of Autologous Chondrocytes Implantation Using ChondroCelect® in Symptomatic Knee Cartilage Lesions in Belgium , 2012, PharmacoEconomics.

[55]  M. Brittberg,et al.  Health economics benefits following autologous chondrocyte transplantation for patients with focal chondral lesions of the knee , 2001, Knee Surgery, Sports Traumatology, Arthroscopy.

[56]  L. Engebretsen,et al.  Knee Cartilage Defect Patients Enrolled in Randomized Controlled Trials Are Not Representative of Patients in Orthopedic Practice , 2010, Cartilage.

[57]  A. Ruano-Raviña,et al.  Spanish Experience in Autologous Chondrocyte Implantation , 2010, The open orthopaedics journal.

[58]  T Minas,et al.  Chondrocyte implantation in the repair of chondral lesions of the knee: economics and quality of life. , 1998, American journal of orthopedics.

[59]  René Verdonk,et al.  Midterm Results of the Treatment of Cartilage Defects in the Knee Using Alginate Beads Containing Human Mature Allogenic Chondrocytes , 2012, The American journal of sports medicine.

[60]  D. Cohen,et al.  Interpreting the results of cost-effectiveness studies. , 2008, Journal of the American College of Cardiology.

[61]  M. Postma,et al.  Need for differential discounting of costs and health effects in cost effectiveness analyses , 2005, BMJ : British Medical Journal.

[62]  G. Verbruggen,et al.  The combination of microfracture and a cell-free polymer-based implant immersed with autologous serum for cartilage defect coverage , 2012, Knee Surgery, Sports Traumatology, Arthroscopy.

[63]  M. Khazzam Commentary & Perspective Augmented Microfracture: Is This the Holy Grail That We Have Been Searching for in the Treatment of Cartilage Injuries? , 2013 .

[64]  Robert C. Grumet,et al.  Surgical management of articular cartilage defects in the knee. , 2009, Instructional course lectures.