Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture

Figures & data

Figure 1. Overview of the Markov model comparing NInject with (i) spheroids of human autologous matrix-associated chondrocytes or (ii) microfracture as 1st repair. Ovals represent the Markov states within the model. Single-headed arrows indicate the potential for unidirectional transition from a Markov state to another. Double-headed arrows indicate the potential for bidirectional transitions. Recursive arrows indicate that notional patients may remain in the current state at the end of the model cycle.

Table 1. Overview of the response and failure rates depending on type of repair.

	Response rates		Failure rates
Type of repair	Rate	Definition	Rate	Definition
Ninject	94.4%^#^26	≥10 points improvement in oKOOS	0.0%^27	Reoperations after 1 year
Spheroids of human autologous matrix-associated chondrocytes	81.0%^14^,^18	"≥10 points improvement in oKOOS"^14	0.0%^14	"Require further surgery"
Microfracture	65.3%^#^26	≥10 points improvement in oKOOS	–	–
oKOOS, Overall Knee injury and Osteoarthritis Outcome Score

^#For Details, see Supplemental Material I.

Table 2. Utility values used in the Markov model (time-dependent), from Mistry et al.¹⁵.

Markov health state	Years	Utility	Reference
Successful 1st repair = NInject or spheroids of human autologous matrix-associated chondrocytes	1st year	0.760	^30
	2nd year	0.817	^30
	3rd year	0.817	^30
	4th year	0.817	^30
	5th year plus	0.817	^30
Successful 1st repair = Microfracture	1st year	0.760	^30
	2nd year	0.817	^30
	3rd year	0.817	^30
	4th year	0.817	^30
	5th years plus	0.654	^30
Successful 2nd repair = NInject or spheroids of human autologous matrix-associated chondrocytes	1st year	0.760	^30
	2nd year	0.817	^30
	3rd year	0.817	^30
	4th year	0.817	^30
	5th year plus	0.817	^30

Table 3. Utility values used in the Markov model (time-independent), from Mistry et al.¹⁵.

Markov health state	Utility	Reference
1st repair	0.654	^30
Successful 1st repair	See Table 2	^30
2nd repair	0.654	^30
No further repair	0.691	^30
Successful 2nd repair	See Table 2
1st TKR/PKR	0.615	^31^,^32
Successful 1st TKR/PKR	0.780	^31
Further TKR/PKR	0.557	^30
Successful further TKR/PKR	0.780	^31
No further TKR/PKR	0.691	^30

Table 4. Overall costs used in the Markov model.

Markov health state	Costs in GBP 2015/16 based on the STA^14^,^22	%	Costs in GBP inflated to 2021 values
1st/2nd repair (=M-ACI)	₤14,961	100%	₤16,659
Costs of cells	₤10,000	67%	–
Harvesting	₤870	6%	–
Implementation	₤2,396	16%	–
Costs for OV	₤110 (per OV) * 6 = ₤660	4%	–
Costs for RV	₤345 (per RV) * 3 = ₤1,035	7%	–
1st repair (= microfracture)	₤4,487	100%	₤4,996
Procedure costs	₤3,122	70%	–
Costs for OV	₤110 (per OV) * 3 = ₤330	7%	–
Costs for RV	₤345 (per RV) * 3 = ₤1,035	23%	–
1st TKR/PKR	₤5,786	100%	₤6,443
Procedure costs	₤5,566	96%	–
Costs for OV	₤110 (per OV) * 2 = ₤220	4%	–
Further TKR/PKR	₤9,701**	100%	₤10,801
TKR following PKR (50%*)	₤5,786 (50%*)		–
Procedure costs	₤5,566	29%	–
Costs for OV	₤110 (per OV) * 2 = ₤220	1%	–
TKR following TKR (50%*)	₤13,617 (50%*)		–
Procedure costs	₤13,397	69%	–
Costs for OV	₤110 (per OV) * 2 = ₤220	1%	–

Abbreviations. OV, outpatient visits; RV, rehabilitation visits.

The percentages refer to the respective subcategory indicated in bold.

*Equal distribution (50%/50%) of notional patients that receive a TKR after either PKR or TKR.

**(₤5,786*50%)+(₤13,617*50%) = ₤9,701.

Table 5. Total lifetime costs and quality-adjusted life-years (QALYs) for notional patients treated with NInject, spheroids of human autologous matrix-associated chondrocytes, or microfracture, and calculation of the incremental cost-effectiveness ratios (ICERs) comparing NInject to (i) spheroids of human autologous matrix-associated chondrocytes or (ii) microfracture.

Intervention	Total costs (₤)*	Total QALYs*	ICER (₤ per QALY)
Ninject	19,036	18.250	–
Spheroids of human autologous matrix-associated chondrocytes	18,772	17.874	–
Microfracture	5,517	15.623	–
Incremental
(i) Spheroids of human autologous matrix-associated chondrocytes	265	0.376	ext. dominated
(ii) NInject vs. microfracture	13,518	2.627	5,147

Abbreviations. QALY, quality-adjusted life year; ICER, incremental cost-effectiveness ratio.

*Rounding differences are possible.

Figure 2. Tornado diagram for sensitivity analyses for NInject compared to microfracture. The first five variables having the most impact on the base case ICER [₤5,147] are ranked top to bottom in the order of decreasing impact.

Note. Values to the right indicate ICER when changing base case values by +20%. Values to the left indicate ICER when changing base case values by ‒20%.

Figure 3. Scatter Plot of Monte Carlo simulation of total costs and QALYs. Red squares present results for microfracture, blue circles for spheroids of human autologous matrix-associated chondrocytes and green crosses for NInject. Due to clear representation, the scatter plot shows only 1,000 iterations of the Monte Carlo simulation.

Figure 4. Cost-effectiveness acceptability frontier.

Figure 5. Value of information analysis - Expected value of perfect information and expected value of parameter perfect information per notional patient. EVPI was based on 100,000 Monte Carlo iterations. EVPPI was based on 100 and 200 Monte Carlo iterations for the inner and outer loop, respectively. Abbreviations. Expected value of perfect information; EVPPI, expected value of parameter perfect information; NFR, no further repair; KR, knee replacement.

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