The cost of care is driven by a large number of market influences both related and unrelated to the quality of treatment provided. Macroeconomic considerations that are the result of underlying economic conditions can play as much a role in cost of care as microeconomic considerations such as the cost of the materials or manufacture of some piece of technology. As such cost cannot be considered a measure of success in a bubble, but can be a piece of the puzzle as we struggle to understand which treatments should be embraced and which should be abandoned. The field of cost effectiveness analysis has given us a way to quantify which medical interventions are worthwhile and should be considered in any health policy decision.
As this is an international conference, we cannot look at cost purely from a USA, or even EU perspective. Macroeconomic considerations such as cost of living, real estate costs, income rates, tax policy, and many others can influence the cost of a given medical intervention in a given geographic region. Likewise, the cost of an individual medical technology will be largely influenced by these macroeconomic forces in the country where the technology is being produced. Likewise, the microeconomic issues related to the country of origin can also have a large influence on cost. However, in reality, these considerations are beyond the scope of our main question: should cost be a measure of success, except to say that cost needs to be considered in this context.
The most reasonable way to consider cost in the measurement of the success of a medical intervention is through cost effectiveness analysis where the effectiveness of treatment is balanced against its cost. In this area of research, a modestly effective intervention that is very expensive may, in fact, be less desirable than a less effective intervention that is much less expensive. At risk of evoking cries of “death panels”, these economic considerations are a reality for any modern medical system.
At its most basic level, cost effective analysis involves dividing the cost of an intervention in monetary units by the expected health gain measured in units such as number of lives saved. Some analyses use other units to measure health gain, such as years of life lost. Another common practice is to discount both health gains and costs in distant years, so that interventions with an immediate impact are deemed more valuable. To add further nuance to cost-effective analysis, other measures have been implemented that distinguish between added years of life in perfect health and added years of life with some health impairment. For example, the quality-adjusted life year (QALY) measures both the additional years of life gained by an intervention and the improved health that is enjoyed as a consequence.
Measures like QALY allow for comparison between interventions that are aimed directly at reducing mortality and those that reduce the severity of illness and improve quality of life. Despite this improvement, there are still challenges to using cost-effective analysis. To start, comparable units are required to measure costs; generally, market exchange rates are used to simulate actual financial constraints. Researchers also need to outline the health interventions being analyzed in detail, and decide how narrowly or broadly associated costs will be defined. Definitions of interventions, scope of costs, and prices to be included can greatly alter interpretation of the cost-effectiveness ratio.
When there is a large difference in the cost-effectiveness ratio of two interventions, policy decisions can be straightforward. When only small differences exist, closer analysis may be necessary, and cost-effectiveness analysis is not as helpful. Cost-effectiveness analysis is also more powerful when interventions that address the same disease or risk factor are compared. In this scenario, other factors still need to be taken into account, like differential access to interventions across populations, disease burden, upfront costs, coverage of existing interventions, and local prices and availability of inputs.
It is not unusual to hear orthopaedic surgeons comment that restorative procedures such as autologous chondrocyte implantation or osteochondral allografts are expensive. However, what should matter is not the cost of the procedure, but its cost-effectiveness.
Cost-effectiveness analysis includes all costs and all benefits, over an appropriate duration, which can be as long as a lifetime. Costs should consider not just the cost of the procedure, but also the costs of alternative treatments, if ACI or OCA was not available, in order to produce the net costs. Depending on age and symptoms, the alternative may be a less effective intervention, with less durability and so return of symptoms. The cost and timing of knee arthroplasty should also be considered. In economics, a cost postponed is a cost reduced, because of discounting. So an intervention that postponed TKA may result in cost-saving to offset the initial procedure cost.
The benefits should be summarised as quality adjusted life years (QALYs), taking account of relief of symptoms and return to usual activities, such as sport or occupation, and hence quality of life, ideally using a generic measure such as EQ5D, to allow comparison with other uses of scarce health care funds.
Cost-effectiveness is reported as the cost per QALY. Thresholds vary amongst countries. In the UK the starting threshold used by the National Institute for Clinical Excellence (NICE) is £20,000 per QALY, but treatments with higher costs per QALY are funded. A key criterion is strength of evidence of clinical effectiveness.
Autologous chondrocyte implantation in the knee.
In the UK, ACI has been approved by NICE subject to certain restrictions, based on the cost per QALY (which means that some unapproved uses might be approved if the price of the cells was reduced). Approval required several appraisals, and took many years because of the need for long-term data, and for trials – the earliest evidence came from case series. This presentation will include an account of the NICE ACI saga.
Osteochondral allografts in the knee
ESSKA commissioned us to do a health technology report on the use of allografts in the knee. The report has been published on the ESSKA website with short versions in the June 2019 issue of the journal KSSTA. We concluded that osteochondral allografting in the knee was highly cost-effective, but that conclusion was based on case series and historical natural history studies.
We concluded that meniscal allograft implantation was probably cost-effective but the available evidence was insufficient to be sure, being mainly from uncontrolled case series and one pilot RCT.
Evidence needs in knee interventions – some key points;
Case series do not usually provide sufficient evidence for cost-effectiveness analysis. We need data on outcomes for the best alternative care so we need more trials, of sufficient duration
We need to identify short-term (e.g. 2-4 years) outcomes that are reliable guides to long-term (20 year) outcomes
It is not enough to say that treatment A is better than treatment B – we need to know how much better A is (the “effect size”)
There are tried and tested outcome measure such as KOOS but for economic analysis we need generic “utility” measures such as EQ5D, in order to provide results in the common currency of cost per QALY. Decisions for funders of care involve assessing costs and benefits of investing in the whole spectrum of possible care. So orthopaedics has to compete with, e.g., new cancer drugs.
There are several new forms of ACI coming, including one-stage versions – we need proper trials set up as soon as data on proof of concept are available.
We need a longer-term trial of meniscal allograft implantation against optimised conservative care.
We need trials of OCA versus ACI
Most of the existing studies come from centres of excellence. Will their results be replicated in routine care?
It would be good to have some multi-centre and indeed multinational trials
Conclusion. Some orthopaedic interventions that might be perceived as expensive, are cost-effective.
Mistry H, Connock M, Pink J, Shyangdan D, Clar C, Royle P, Court R, Biant LC, Metcalfe A, Waugh N. Autologous chondrocyte implantation in the knee: systematic review and economic evaluation. Health Technology Assessment 2017/21/ number 6
Waugh N, Mistry H, Metcalfe A, Colquitt J, Loveman E, Royle P, Smith NA. . Allografts in reconstruction of the posterior cruciate ligament: a health economics perspective. Knee Surg Sports Traumatol Arthrosc. 2019/27/1810-16. doi: 10.1007/s00167-019-05477-4.
Waugh N, Mistry H, Metcalfe A, Loveman E, Colquitt J, Royle P, Smith NA, Spalding T. Meniscal allograft transplantation after meniscectomy: clinical effectiveness and cost-effectiveness. Knee Surg Sports Traumatol Arthrosc 2019/27/1825-46 doi.org/10.1007/s00167-019-05504-4
Waugh N, Mistry H. A brief introduction to health economics. Knee Surg Sports Traumatol Arthrosc. 2019/27/1704-1707. doi: 10.1007/s00167-019-05372-y.
Mistry H, Metcalfe A, Colquitt J, Loveman E, Smith NA, Royle P, Waugh N. Autograft or allograft for reconstruction of anterior cruciate ligament: a health economics perspective. Knee Surg Sports Traumatol Arthrosc. 2019/27/1782-90. doi: 10.1007/s00167-019-05436-z.
Mistry H, Metcalfe A, Smith N, Loveman E, Colquitt J, Royle P, Waugh N. The cost-effectiveness of osteochondral allograft transplantation in the knee. Knee Surg Sports Traumatol Arthrosc. 2019/27/1739-53. doi: 10.1007/s00167-019-05392-8.
Our review of the use of allografts in knee reconstructions was funded by the European Society of Sport Traumatology, Knee Surgery and Arthroscopy.
Autologous chondrocytes transplantation is the best documented cartilage repair modality both regarding clinical outcome and biological cartilage repair tissue quality. But the high cost (20-30.000 USD) of cultured cell-based techniques such as autologous chondrocyte implantation (ACI) and new tissue engineered products for articular cartilage repair have limited their use in most countries. Microfracture is the standard cost-effective cartilage repair modality, but the technique has limitations in which lesions that can respond to microfracture treatment, the repair tissue quality and longevity of the clinical outcome.
This has led to increased focus on development of cost-effective cartilage repair methods that avoid cultured cell products and that can improve or out-perform the clinical outcome of standard microfracture treatment. At the present state the following cartilage repair treatment methods have aimed to fulfil the goals of cost-effective cartilage repair
Microfracture enhancing scaffolds
To overcome the disadvantages of microfracture and ACI, a new treatment option has evolved: the single-step scaffold-based treatment of cartilage defects. During this approach, a matrix is implanted in the area of the damaged cartilage to cover the blood
clot after a bone marrow stimulation technique (e.g. microfracture). This technique is also called autologous matrix-induced chondrogenesis (AMIC). The scaffolds are implanted arthroscopically or by a mini-arthrotomy for ‘‘in situ’’ repair, permitting the ingrowing of
mesenchymal stem cells (MSCs) to differentiate into the chondrogenic lineage.
Numerous techniques for microfracture enhancement have been developed. Collagen and hyaluronic acid scaffold application on top of the microfractured area.(de Girolamo 2019) Also, different hydrogels that are applied on top of the microfractured area are development. These hydrogels are based on chitosan, collagen or fibrinogen.(Shive 2015) Several of the microfracture enhancers have demonstrated midterm clinical usage with clinical outcome improvement similar to ACI.
Cost of microfracture enhancer from 1000-2500 USD
Bone marrow cell transplantation
One-step cell-based repair techniques with scaffold associated multipotent cells sourced from bone marrow aspirate concentrate (BMAC) have demonstrated excellent medium-term outcomes in large lesions of comparable size to those treated by 2-step cultured chondrocytes cell-based procedures.(Gobbi 2019). The technique is based on external cells stimulation of cartilage repair by transplanting concentrated bone marrow cells mixed with PRP seeded on a scaffold and fixed with fibrin glue in the cartilage defect. The concept of repair is that the stemcells in marrow cell concentrate can in combination with the growth factors in the platelet rich plasma initiate formation of cartilage repair tissue.
The cost of bone marrow cell transplantation (kits for BMAC and PRP concentration 500 USD)
Autologous cartilage chips implantation
Implantation of Articular Cartilage Chips (ACC) is a principle to implant mature hyaline cartilage into a cartilage defect. This method has been investigated in osteochondral defects in knee where the bone defect were transplanted with autologous cancellous bone from the tibia and the cartilage layer was recreated by cartilage chips from cartilage biopsies taken from the intercondylar notch, the lateral femoral condyles edge or other low weight bearing area, and the cartilage biopsies were chopped into small cartilage chips <0.25-0.5 cm3. The chips are implanted and embedded in fibrin glue.
One clinical study has presented outcome data for the technique. In the study eight patients with osteochondral defects due to osteochondritis dissicans were treated with the combine bone and cartilage chips transplantation. (Christensen 2015) At one-year follow-up subjective outcome improved for IKDC from 39 preoperatively to 68 at one year. Also, KOOS and Tegner scores improved. Healing response based on MR MOCART scores improved from 23 to 53. All patient demonstrated good subchondral bone healing based on CT scanning.
The cost of autologous chips transplantation (0 USD)
Gobbi A, Whyte GP. Long-term Clinical Outcomes of One-Stage Cartilage Repair
in the Knee With Hyaluronic Acid-Based Scaffold Embedded With Mesenchymal Stem
Cells Sourced From Bone Marrow Aspirate Concentrate. Am J Sports Med. 2019
Christensen BB, Foldager CB, Jensen J, Lind M. Autologous Dual-Tissue
Transplantation for Osteochondral Repair: Early Clinical and Radiological
Results. Cartilage. 2015 Jul;6(3):166-73.
Shive MS, Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J,
Méthot S, Vehik K, Restrepo A. BST-CarGel® Treatment Maintains Cartilage Repair
Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled
Trial. Cartilage. 2015 Apr;6(2):62-72.
de Girolamo L, Schönhuber H, Viganò M, Bait C, Quaglia A, Thiebat G, Volpi P.
Autologous Matrix-Induced Chondrogenesis (AMIC) and AMIC Enhanced by Autologous
Concentrated Bone Marrow Aspirate (BMAC) Allow for Stable Clinical and Functional
Improvements at up to 9 Years Follow-Up: Results from a Randomized Controlled
Study. J Clin Med. 2019 Mar 21;8(3). pii: E392. doi: 10.3390/jcm8030392.