Economic outcomes among Medicare patients receiving bioengineered cellular technologies for treatment of diabetic foot ulcers

Figures & data

Figure 1. Selection of BLCC/HFDS and CC patients. BLCC: bioengineered living cellular construct; CC: conventional care; DFU: diabetic foot ulcer; HBO: hyperbaric oxygen; HFDS: human fibroblast-derived dermal substitute; HMO: health maintenance organization. *Total patient population includes all Medicare beneficiaries in the 5% Standard Analytic File with at least one medical claim in 2000–2012. †Includes patients with at least two distinct claims with a diabetes diagnosis (ICD-9-CM: 249.xx, 250.xx) and at least one claim with a foot ulcer diagnosis (ICD-9-CM: 707.10, 707.14 707.15, 707.19, 707.8, 707.9) on or after the first diabetes diagnosis at any time in 2000–2012 (the date of foot ulcer diagnosis was considered as the DFU diagnosis date). ‡Patients were required to have at least one claim for the specified skin substitute within 12 months following a DFU diagnosis (as defined above). Patients were not permitted to have a claim for the specified treatment during the 12 months preceding the treatment. §Patients were required to have no claims for skin substitutes at any time in 2000–2012 and were required to have at least one claim with either a DFU diagnosis, DFU-related procedure (debridement, drainage and incision, offloading, negative pressure wound therapy, HBO procedure), or a podiatrist visit. ||The study period was defined as the 12 months prior to and 18 months following the start of new treatment (index date) for the BLCC/HFDS patients, and following a random DFU-related claim (as defined above) meeting all sample selection criteria for the conventional care patients.

Table 1. Patient characteristics during the 12 months prior to the index date: BLCC vs CC.

	Pre-match characteristics			Post-match characteristics
	BLCC (n = 921)	CC (n = 19,758)	p*	BLCC (n = 502)	CC (n = 502)	p†
Demographics
Age,‡ mean (SD)	76.4 (7.2)	76.3 (7.5)	0.5856	75.4 (6.7)	75.4 (6.7)	0.7547
Male, %	46.8	46.3	0.7493	49.8	48.6	0.7087
Comorbidities, %
Diabetes with chronic complications	70.4	49.7	<0.0001	69.5	69.9	0.8907
Peripheral vascular disease	66.3	38.6	<0.0001	61.6	63.7	0.4711
Atherosclerosis	42.8	21.0	<0.0001	39.8	40.4	0.8504
Congestive heart failure	41.4	32.8	<0.0001	42.0	38.0	0.1986
Dermatophytosis of nail	39.0	34.1	0.0022	37.1	36.3	0.8003
Renal disease	31.8	22.2	<0.0001	31.9	29.7	0.4531
Obesity	19.8	12.4	<0.0001	18.1	18.5	0.8711
Depression	16.6	16.3	0.7781	14.5	16.7	0.3365
Any malignancy including leukemia and lymphoma	12.9	12.5	0.6763	12.7	14.1	0.5245
Deep vein thrombosis	9.2	5.2	<0.0001	8.8	10.6	0.3346
Phlebitis	6.1	3.1	<0.0001	5.6	7.2	0.3017
Wound severity measures
Quarters of active ulceration,§ mean (SD)	2.1 (1.5)	1.4 (1.6)	<0.0001	1.9 (1.5)	1.9 (1.5)	0.9470
Unique ulcer diagnoses,|| mean (SD)	3.2 (2.4)	1.2 (1.6)	<0.0001	2.7 (2.3)	2.8 (2.7)	0.5373
DFU-related infection,¶ %	60.3	30.9	<0.0001	55.8	57.4	0.5978
Lower-limb amputation, %	8.0	3.2	<0.0001	8.6	8.0	0.7357
DFU-related medical costs,# mean (SD)	$17,406 ($27,201)	$4,612 ($14,535)	<0.0001	$15,248 ($26,236)	$15,940 ($27,315)	0.7943
Physician experience measures, mean (SD)
Advanced wound care patients	1.7 (1.6)	0.1 (0.4)	<0.0001	1.4 (1.1)	1.2 (1.5)	0.0033
Foot ulcer claims	51.1 (58.6)	18.0 (27.9)	<0.0001	46.0 (49.1)	48.4 (48.5)	0.1637
HBO claims	9.0 (25.9)	1.2 (8.3)	<0.0001	7.9 (22.6)	8.8 (25.0)	0.1863

BLCC: bioengineered living cellular construct; CC: conventional care; DFU: diabetic foot ulcer; HBO: hyperbaric oxygen; SD: standard deviation.

*Calculated using Wilcoxon-rank sum tests for continuous variables and chi-square tests for categorical variables.

†Calculated using Wilcoxon signed-rank tests for continuous variables and McNemar’s tests for categorical variables.

‡Age was evaluated as of the quarter preceding the index date.

§Quarters of active ulceration was calculated as the number of quarters from the earliest DFU diagnosis in the 12-month baseline period to the index date.

||A unique ulcer diagnosis was defined as any occurrence of a chronic skin ulcer 5-digit ICD-9-CM code (707.xx).

¶DFU-related infections include cellulitis, osteomyelitis, periostitis, gangrene, and other infections of lower extremity bone.

#DFU-related medical costs include costs for claims with at least one DFU or DFU-related infection diagnosis, an amputation procedure, a DFU-related treatment (i.e. debridement, drainage and incision, offloading, negative pressure wound therapy, HBO), or a podiatry visit. Dollar values were inflated to 2012 USD using the medical care component of the Consumer Price Index.

Table 2. Patient characteristics during the 12 months prior to the index date: HFDS vs CC.

	Pre-match characteristics			Post-match characteristics
	HFDS (n = 443)	CC (n = 19,758)	p*	HFDS (n = 222)	CC (n = 222)	p†
Demographics
Age,‡ mean (SD)	74.3 (6.6)	76.3 (7.5)	<0.0001	73.9 (6.2)	73.9 (6.3)	0.4618
Male, %	62.3	46.3	<0.0001	58.1	68.0	0.0326
Comorbidities, %
Diabetes with chronic complications	88.5	49.7	<0.0001	83.8	84.7	0.7855
Peripheral vascular disease	64.8	38.6	<0.0001	56.8	61.3	0.3173
Atherosclerosis	44.7	21.0	<0.0001	38.3	37.8	0.9215
Congestive heart failure	43.6	32.8	<0.0001	37.4	37.4	1.0000
Dermatophytosis of nail	42.0	34.1	0.0005	38.7	46.8	0.0804
Renal disease	39.1	22.2	<0.0001	32.0	38.7	0.1356
Depression	17.4	16.3	0.5279	18.0	14.4	0.3017
Obesity	17.2	12.4	0.0030	16.2	20.7	0.2450
Any malignancy including leukemia and lymphoma	14.2	12.5	0.2664	12.2	15.3	0.3452
Deep vein thrombosis	7.2	5.2	0.0556	5.4	9.0	0.1573
Phlebitis	4.1	3.1	0.2649	1.8	0.9	0.4142
Wound severity measures
Quarters of active ulceration,§ mean (SD)	2.2 (1.5)	1.4 (1.6)	<0.0001	2.0 (1.5)	2.0 (1.6)	0.5290
Unique ulcer diagnoses,|| mean (SD)	2.8 (2.3)	1.2 (1.6)	<0.0001	2.4 (2.1)	2.5 (2.6)	0.8128
DFU-related infection,¶ %	61.4	30.9	<0.0001	53.6	56.8	0.5469
Lower-limb amputation, %	15.8	3.2	<0.0001	13.5	11.7	0.5716
DFU-related medical costs, # mean (SD)	$18,412 ($30,834)	$4,612 ($14,535)	<0.0001	$14,279 ($25,175)	$12,835 ($24,012)	0.3796
Physician experience measures, mean (SD)
Advanced wound care patients	1.6 (1.1)	0.1 (0.4)	<0.0001	1.4 (1.1)	1.1 (1.5)	0.0019
Foot ulcer claims	49.7 (41.7)	18.0 (27.9)	<0.0001	48.6 (43.4)	41.7 (40.0)	0.0327
HBO claims	7.5 (24.6)	1.2 (8.3)	<0.0001	8.5 (28.9)	5.4 (19.4)	0.7121

CC: conventional care; DFU: diabetic foot ulcer; HBO: hyperbaric oxygen; HFDS: human fibroblast-derived dermal substitute; SD: standard deviation.

*Calculated using Wilcoxon-rank sum tests for continuous variables and chi-square tests for categorical variables.

†Calculated using Wilcoxon signed-rank tests for continuous variables and McNemar’s tests for categorical variables.

‡Age was evaluated as of the quarter preceding the index date.

§Quarters of active ulceration was calculated as the number of quarters from the earliest DFU diagnosis in the 12 month baseline period to the index date.

||A unique ulcer diagnosis was defined as any occurrence of a chronic skin ulcer 5-digit ICD-9-CM code (707.xx).

¶DFU-related infections include cellulitis, osteomyelitis, periostitis, gangrene, and other infections of lower extremity bone.

#DFU-related medical costs include costs for claims with at least one DFU or DFU-related infection diagnosis, an amputation procedure, a DFU-related treatment (i.e. debridement, drainage and incision, offloading, negative pressure wound therapy, HBO), or a podiatry visit. Dollar values were inflated to 2012 USD using the medical care component of the Consumer Price Index.

Table 3. Healthcare resource use and costs during the 18-month follow-up period among BLCC/HFDS patients vs respective matched CC patients.

	BLCC vs matched CC comparison			HFDS vs matched CC comparison
	BLCC (n = 502)	CC (n = 502)	p*	HFDS (n = 222)	CC (n = 222)	p*
Lower-limb amputations, %	11.8	16.3	0.0350	18.9	24.3	0.1904
Above knee	2.0	5.6	0.0020	1.4	5.0	0.0325
Below knee	3.0	5.8	0.0269	4.5	6.8	0.3173
Foot	8.2	9.2	0.5688	16.2	16.7	0.9013
Total medical resource use, mean (SD)
Inpatient days	10.6 (19.9)	15.9 (25.7)	<0.0001	9.9 (16.2)	17.2 (27.2)	0.0010
Emergency department visits	4.4 (5.7)	6.5 (10.6)	<0.0001	5.2 (7.6)	7.0 (8.6)	0.0079
Outpatient/physician visits	139.0 (83.1)	118.6 (89.8)	<0.0001	137.9 (77.3)	118.8 (81.0)	0.0055
Home health days	3.0 (3.9)	2.9 (3.9)	0.5237	2.7 (3.8)	2.6 (3.6)	0.6666
Other visits	13.0 (12.3)	15.5 (16.3)	0.0841	15.2 (13.7)	16.3 (15.7)	0.5586
Total medical costs,† mean (SD)	$62,809 ($61,662)	$68,062 ($76,360)	0.4885	$66,063 ($58,246)	$73,054 ($81,858)	0.8380
Inpatient	$18,340 ($32,830)	$26,868 ($44,841)	0.0021	$17,164 ($27,208)	$31,648 ($48,314)	0.0005
Emergency department	$587 ($950)	$852 ($1,742)	0.0013	$774 ($1,681)	$896 ($1,364)	0.0074
Outpatient/physician	$25,527 ($25,539)	$18,427 ($25,205)	<0.0001	$31,560 ($26,854)	$19,613 ($23,698)	<0.0001
Home healthcare	$9,739 ($14,752)	$9,815 ($17,020)	0.7588	$8,037 ($12,680)	$8,500 ($15,423)	0.9250
Other	$8,617 ($14,859)	$12,100 ($18,844)	0.0085	$8,527 ($14,229)	$12,397 ($21,087)	0.2460
Total medical costs (excluding product and application costs),† mean (SD)	$59,025 ($60,773)	$68,062 ($76,360)	0.7076	$55,953 ($54,922)	$73,054 ($81,858)	0.0814

BLCC: bioengineered living cellular construct; CC: conventional care; HFDS: human fibroblast-derived dermal substitute; SD: standard deviation.

*Calculated using Wilcoxon signed-rank tests for continuous variables and McNemar’s tests for categorical variables.

†Dollar values were inflated to 2012 USD using the medical care component of the Consumer Price Index.