Economic impact and chronic obstructive pulmonary disease outcomes of a comprehensive inhaler to nebulization therapy protocol implementation in a large multi-state healthcare system

Figures & data

Table 1. Current FDA-approved inhalers available on the US market^a.

Inhaler	Active ingredients	Type	Inhaler size (actuations)
Short-acting beta2-agonists (SABAs)
Albuterol HFA^d^,^g	Albuterol sulfate 120 mcg (90 mcg albuterol)	MDI	200
Primatene Mist HFA^b	Epinephrine 0.125 mg	MDI	160
ProAir Digihaler^c	Albuterol sulfate 117 mcg (90 mcg albuterol)	DPI	200
ProAir HFA	Albuterol sulfate 120 mcg (90 mcg albuterol)	MDI	200
ProAir RespiClick	Albuterol sulfate 117 mcg (90 mcg albuterol)	DPI	200
Proventil HFA	Albuterol sulfate 120 mcg (90 mcg albuterol)	MDI	200
Ventolin HFA	Albuterol sulfate 120 mcg (90 mcg albuterol)	MDI	60, 200
Xopenex HFA	Levalbuterol sulfate 59 mcg (45 mcg levalbuterol)	MDI	200
Levalbuterol HFA^d	Levalbuterol tartrate 59 mcg (45 mcg levalbuterol)	MDI	200
Long-acting beta2-agonists (LABAs)
Arcapta Neohaler	Indacaterol maleate 75 mcg	DPI	30
Serevent Diskus	Salmeterol xinafoate 50 mcg	DPI	28, 60
Striverdi Respimat	Olodaterol HCl 2.5 mcg	Mist	60
Short-acting muscarinic antagonists (SAMAs)
Atrovent HFA	Ipratropium bromide 17 mcg	MDI	200
Long-acting muscarinic antagonists (LAMAs)
Incruse Ellipta	Umeclidinium bromide 62.5 mcg	DPI	7, 30
Seebri Neohaler	Glycopyrrolate 15.6 mcg	DPI	6, 60
Spiriva HandiHaler	Tiotropium bromide 18 mcg	DPI	5, 30, 90
Spiriva Respimat	Tiotropium bromide 1.25 mcg, 2.5 mcg	Mist	10, 28, 60
Tudorza Pressair	Aclidinium bromide 400 mcg	DPI	30, 60
Short-acting muscarinic antagonist (SAMA)/short-acting beta2-agonists (SABAs)
Combivent Respimat	Ipratropium bromide/albuterol sulfate 20/100 mcg	Mist	120
Inhaled corticosteroids (ICSs)
Alvesco HFA	Ciclesonide 80 mcg, 160 mcg	MDI	60
ArmonAir RespiClick^d	Fluticasone propionate 55 mcg, 113 mcg, 232 mcg	DPI	60
Arnuity Ellipta	Fluticasone furoate 50 mcg, 100 mcg, 200 mcg	DPI	14, 30
Asmanex HFA	Mometasone furoate 100 mcg, 200 mcg	MDI	120
Asmanex Twisthaler	Mometasone furoate 110 mcg, 220 mcg	DPI	14, 30, 60
Flovent Diskus	Fluticasone propionate 50 mcg, 100 mcg, 250 mcg	DPI	28, 60
Flovent HFA	Fluticasone propionate 44 mcg, 110 mcg, 220 mcg	MDI	120
Pulmicort Flexhaler	Budesonide 90 mcg, 180 mcg	DPI	60, 120
Qvar Redihaler HFA	Beclomethasone dipropionate 40 mcg, 80 mcg	MDI	120
Inhaled corticosteroid (ICS)/long-acting beta2-agonists (LABAs)
Advair Diskus^h	Fluticasone propionate/salmeterol 100/50 mcg, 250/50 mcg, 500/50 mcg	DPI	14, 60
Advair HFA	Fluticasone propionate/salmeterol 45/21 mcg, 115/21 mcg, 230/21 mcg	MDI	60, 120
AirDuo RespiClick^d	Fluticasone propionate/salmeterol 55/14 mcg, 113/14 mcg, 232/14 mcg	DPI	60
Breo Ellipta	Fluticasone furoate/vilanterol 100/25 mcg, 200/25 mcg	DPI	14, 30
Dulera	Mometasone furoate/formoterol fumarate dihydrate 100/5 mcg, 200/5 mcg	MDI	60, 120
Symbicort HFA	Budesonide/formoterol fumarate dihydrate 80/4.5 mcg, 160/4.5 mcg	MDI	60, 120
Wixela Inhub^e	Fluticasone propionate/salmeterol 100/50 mcg, 250/50 mcg, 500/50 mcg	DPI	60
Long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonists (LABAs)
Anoro Ellipta	Umeclidinium bromide/vilanterol 62.5/25 mcg	DPI	7, 30
Bevespi Aerosphere	Glycopyrrolate/formoterol fumarate 9/4.8 mcg	MDI	28, 120
Duaklir Pressair^f	Aclidinium bromide/formoterol fumarate 400/12 mcg	DPI	30, 60
Stiolto Respimat	Tiotropium bromide/olodaterol HCl 2.5/2.5 mcg	Mist	10, 28, 60
Utibron Neohaler	Glycopyrrolate/indacaterol 15.6/27.5 mcg	DPI	6, 60
Inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonists (LABAs)
Trelegy Ellipta	Fluticasone furoate/umeclidinium/vilanterol 100/62.5/25 mcg	DPI	14, 30

^a Information derived from McKesson and package inserts provided by inhaler manufacturers.

^b Over-the-counter (OTC) inhaler. FDA approved 8 November 2018.

^c First FDA-approved inhaler with built in sensors to monitor use and inspiratory flow via Bluetooth Wireless Technology. FDA approved 21 December 2018. Availability via Early Experience programs in 2019. National launch planned for 2020.

^d Generic or “branded-generic” Teva Pharmaceuticals inhalers. AirDuo Respiclick and ProAir HFA also available as authorized generics.

^e FDA approved 30 January 2019. Mylan Pharmaceuticals. Therapeutically equivalent generic of Advair Diskus.

^f FDA approved 29 March 2019. Circassia Pharmaceuticals/AstraZeneca. National launch planned for second half 2019.

^g Authorized generics available 2019. PAR Pharmaceuticals (authorized generic for Proventil HFA). Prasco Laboratories (authorized generic for Ventolin HFA). Teva Pharmaceuticals (authorized generic for ProAir HFA).

^h Authorized Advair generic available 2019. Prasco Laboratories. Only available in 60 dose DPIs.

Table 2. Inhaler to nebulization protocol.

Ordered inhaler^a	Nebulized regimen
Short-acting beta2-agonists (SABAs)^c	Albuterol Neb 1.25 mg–2.5 mg same frequency
Short-acting muscarinic antagonists (SAMAs)^c	Ipratropium 0.5 mg Neb same frequency
Long-acting muscarinic antagonists (LAMAs)^c	Ipratropium 0.5 mg Neb Q6H
Long-acting beta2-agonists (LABAs)	Arformoterol 15 mcg Neb BID
Short-acting muscarinic antagonist (SAMA)/short-acting beta2-agonists (SABAs)^c	Ipratropium/albuterol 0.5 mg/2.5 mg Neb same frequency
Long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonists (LABAs)^c	Ipratropium 0.5 mg Neb Q6H + arformoterol 15 mcg Neb BID
Inhaled corticosteroids (ICSs)	Budesonide 0.25 mg–0.5 mg BID^b
Inhaled corticosteroid (ICS)/long-acting beta2-agonists (LABAs)	Budesonide 0.25 mg–0.5 mg BID^b + arformoterol 15 mcg Neb BID
Inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonists (LABAs)^c	Budesonide 0.5 mg Neb BID + ipratropium 0.5 mg Neb Q6H + arformoterol 15 mcg Neb BID

^a Refer to Table 1. Primatene Mist HFA (OTC) not included.

^b Dose utilized dependent on inhaler and dosage.

^c If patient already on ipratropium/albuterol SVN, do not add ipratropium and/or albuterol component to avoid duplications.

Table 3. Annual net drug expenditures and inhaler purchases of each facility: inhalers, nebulized medications and total combined.

Campus	34OB^b	Beds	Phase^d	INHALER PRE ($)	INHALER PY1 ($)	INHALER PY2 ($)	NEB Pre ($)	NEB PY1 ($)	NEB PY2 ($)	Total PRE ($)	Total PY1 ($)	Total PY2 ($)	Reduction PY1 ($)^f	Reduction PY2 ($)^f	INH Pre^i	INH PY1^i	INH PY2^i
1^a	340B-DSH	657	1	389,123	81,071	35,482	162,204	267,895	303,050	551,327	348,965	338,532	−202,362 (36.7%)	−212,795 (38.6%)	7857	3826	3157
2^e	340B-DSH	561	2	437,266	85,638	25,164	113,379	258,666	210,944	550,644	344,304	236,108	−206,340 (37.5%)	−314,536 (57.1%)	8050	2965	1261
3	340B-DSH	157	3	80,371	5998	2484	56,664	89,852	83,367	137,035	95,850	85,851	−41,185 (30.1%)	−51,184 (37.4%)	975	134	102
4^c	NON-340B	434	4	307,077	5403	7490	75,236	203,258	239,035	382,313	208,661	246,525	−173,652 (45.4%)	−135,788 (35.5%)	2777	128	167
5^e	NON-340B	384	4	361,098	9627	19,559	33,655	130,816	185,081	394,753	140,443	204,640	−254,310 (64.4%)	−190,113 (48.2%)	4079	169	247
6	NON-340B	20	4	14,683	91	74	4646	5962	12,919	19,329	6053	12,993	−13,276 (68.7%)	−6336 (32.8%)	287	−31^h	4
7	340B-DSH	61	4	15,971	1797	852	6820	17,539	28,303	22,791	19,336	29,154	−3455 (15.2%)	6364 (27.9%)	459	76	27
8^c	NON-340B	359	5	200,390	−2130^h	994	111,498	260,107	272,843	311,888	257,977	273,837	−53,911 (17.3%)	−38,052 (12.2%)	1802	27	53
9^c	NON-340B	111	5	32,847	303	375	31,628	54,793	56,301	64,475	55,096	56,676	−9379 (14.6%)	−7798 (12.1%)	336	13	20
10^g	340B-DSH	729	5	369,425	12,913	4669	125,451	311,415	278,226	494,876	324,328	282,895	−170,548 (34.5%)	−211,980 (42.8%)	5110	511	347
11	340B-DSH	146	5	58,362	−8450^h	1068	14,407	39,221	28,248	72,770	30,771	29,316	−41,999 (57.7%)	−43,454 (59.7%)	1098	−35^h	127
12	340B-CAH	25	5	20,842	−2191^h	199	6197	9357	8440	27,039	7165	8640	−19,874 (73.5%)	−18,399 (68.1%)	302	28	35
13	340B-CAH	25	5	11,514	565	296	1702	5592	4385	13,217	6157	4681	−7060 (53.4%)	−8536 (64.6%)	151	49	34
14	340B-DSH	311	5	136,867	6405	3942	50,158	122,172	116,035	187,025	128,578	119,977	−58,448 (31.3%)	−67,049 (35.9%)	3126	468	418
15	340B-DSH	22	5	19,186	−444^h	1384	1196	6283	6197	20,382	5839	7582	−14,543 (71.4%)	−12,800 (62.8%)	277	110	113
16	340B-CAH	25	5	13,267	6520	3219	2164	3844	2307	15,432	10,364	5526	−5068 (32.8%)	−9906 (64.2%)	239	119	53
17	340B-DSH	165	5	52,696	3312	3619	4113	22,166	22,657	56,809	25,478	26,275	−31,332 (55.2%)	−30,534 (53.7%)	1137	342	351
18	340B-DSH	378	5	145,255	13,642	6051	9909	76,705	89,335	155,163	90,346	95,387	−64,817 (41.8%)	−59,777 (38.5%)	3201	607	572
19	340B-CAH	18	5	10,577	−2887^h	376	1407	2651	2657	11,985	−236	3032	−12,220 (102%)	−8952 (74.7%)	116	1	13
20	340B-CAH	25	5	9202	4621	3213	1512	1068	466	10,714	5689	3680	−5025 (46.9%)	−7035 (65.6%)	154	97	83
21	340B-SOLE	44	5	12,990	309	2499	5192	8908	10,925	18,182	9217	13,424	−8965 (49.3%)	−4758 (26.2%)	131	22	32
22	340B-CAH	25	5	4623	438	437	1548	2494	5195	6171	2932	5632	−3239 (52.5%)	−539 (8.7%)	106	19	24
23	340B-CAH	25	5	11,741	−1064^h	710	3224	6839	10,239	14,964	5775	10,949	−9190 (61.4%)	−4016 (26.8%)	238	30	63
24	340B-CAH	25	5	3844	550	139	1998	4944	4111	5842	5495	4250	−347 (5.9%)	−1592 (27.3%)	87	34	33
25	340B-CAH	25	5	8913	−585^h	167	1920	2636	2305	10,833	2052	2472	−8781 (81.1%)	−8361 (77.2%)	142	27	29
26^e,g	340B-DSH	166	6	56,467	12,852	10,519	9834	44,083	50,376	66,301	56,935	60,894	−9366 (14.1%)	−5407 (8.2%)	2020	434	434
27^g	340B-DSH	478	6	381,102	88,438	73,429	54,646	214,986	169,238	435,747	303,425	242,667	−132,322 (30.4%)	−193,080 (44.3%)	5938	2054	1473
Totals				3,165,699	322,741	208,410	892,307	2,174,253	2,203,184	4,058,006	2,496,995	2,411,594	−1,561,011 (38.5%)	−1,646,411 (40.6%)	50,195	12,224	9272

^a Initial pilot facility of author. Shared campus with pediatric hospital with combined pharmacy cost center.

^b 340B Program eligible hospitals, Disproportionate Share Hospitals (DSHs), Critical Access Hospitals (CAHs), Sole Community Hospital (SOLE).

^c Common Canister facilities.

^d Go Live dates: phase 1 (5 January 2016), phase 2 (18 January 2016), phase 3 (11 April 2016), phase 4 (16 August 2016), phase 5 (20 September 2016), phase 6 (1 November 2016).

^e Facilities with inpatient psychiatric units.

^f Reduction in total drug costs in US dollars and percentage decreases are compared to the 12 month pre-implementation periods for each facility and in aggregate. All US dollars rounded to nearest whole dollar.

^g Academic medical centers, prior EPIC platform facilities.

^h Negative number due to facility crediting back more existing supply post-implementation than purchased during the 12 month period.

ⁱ Net inhalers purchased.

Table 4. Twelve-month arformoterol and budesonide nebulized medication expenditures: total costs and percentage of total overall system respiratory drug costs.

Comparison period	Arformoterol	Units^a	Budesonide^b	Units^a	Combined
Pre-implementation	144,161 (3.6%)	791	433,524 (10.7%)	2223	577,686 (14.2%)
PY1	645,721 (25.9%)	5115	1,211,229 (48.5%)	6961	1,856,950 (74.4%)
PY2	687,796 (28.5%)	5599	1,214,502 (50.4%)	7262	1,902,299 (78.9%)

^a One unit = one box of 30 nebulized doses.

^b NDC:00487-9601-01 (0.25 mg/2 mL UD) and NDC:00487-9701-01 (0.5 mg/2 mL UD) – Nephron Pharmaceuticals.

Table 5. Total system net inhaler purchases.

Inhaler	Pre	% of total	PY1	% of total	PY2	% of total
Fluticasone/salmeterol (Advair Diskus)	13,320	26.5	332	2.7	217	2.3
Flutcasone/salmeterol (Advair HFA)	4763	9.5	156	1.3	162	1.8
Fluticasone (Flovent Diskus)	488	1.0	82	0.7	74	0.8
Fluticasone (Flovent HFA)	3695	7.4	1030	8.4	559	6.0
Tiotropium (Spiriva)	10,823	21.6	937	7.7	124	1.3
Albuterol (Ventolin/Proventil/Proair HFA)	15,872	31.6	9557	78.2	8090	87.3
Ipratropium (Atrovent)/ipratropium/albuterol (Combivent)	705	1.4	52	0.4	13	0.1
Other^a	529	1.1	78	0.6	33	0.4
Totals	50,195	100.0	12,224	100.0	9272	100.0

^a Mometasone (Asmanex HFA), fluticasone/vilanterol (Breo Ellipta), mometasone/formoterol (Dulera), formoterol (Foradil), budesonide (Pulmicort Flexhaler), beclomethasone (Qvar RediHaler), salmeterol (Serevent Diskus), budesonide/formoterol (Symbicort HFA), levalbuterol (Xopenex HFA).

Table 6. Potential roles of respiratory therapists.

Small volume nebulization (SVN – continuous and regular)

Respiratory assessment and treatment protocols

Lung expansion therapy (Metaneb, EZ pap, flutter)

Vest therapy

Chest percussion

Conscious sedation standby

Arterial blood gases (draws and analyzing)

Bi-pap therapy

Bronchoscopy assist

Ventilator management (ICU and interventional radiology)

Nitric oxide administration

Airway management

Rotoprone airway management

Intubation (neonatal intensive care unit–NICU)

Intubation assist

Altitude studies (NICU)

Extubation

Trach changes (pediatric)

Trach management/care

Trach education(pediatric)

PICC and arterial placement and management

Extracorporeal membrane oxygenation (ECMO)

Pulmonary function tests (PFTs – bedside and complete)

MRI ventilator management

Transports

Nitric studies (cath lab)

Pentamidine and antibiotic nebulization treatments

Code/rapid response

Equipment cleaning and set-up

Pediatric cardiac patient care

Ambulation studies

Electrocardiograms (EKGs)

Asthma education

COPD assessment/education

Table 7. Comparison of system patient volumes, case mix index, chronic obstructive pulmonary disease readmissions, and length of stay.

Variable	Pre-Implementation	PY1	PY2
No. adjusted patient days	2,001,246	2,057,408	2,058,104
CMI-COPD^a	1.05	1.08	1.06
COPD 30 day readmission – overall	15.7% (n = 4939)	14.7% (n = 5550)	14.5% (n = 5321)
COPD 30 day readmission – Medicare	15.1% (n = 3129)	13.6% (n = 3603)	15.2% (n = 3363)
COPD LOS – overall	4.5	4.7	4.9

^a DRGs 190, 191, 192.

Table 8. Campus 1 respiratory outcomes data.

Variable	Pre-implementation	PY1	PY2	PY3
CMI – COPD^a	1.05	1.06	1.05	N/A
COPD 30 day readmission – overall	21.0% (n = 656)	17.5% (n = 612)	17.7% (n = 896)	14.5% (n = 634)
COPD 30 day readmission – Medicare	20.8% (n = 346)	14.4% (n = 327)	15.9% (n = 511)	14.5% (n = 337)
COPD LOS – overall	5.1	5.1	5.3	5.3
Pediatric asthma LOS	1.8	1.9	1.8	N/A^b
Pediatric asthma readmissions – 30 day	2.1% (n = 329)	2.2% (n = 314)	2.9% (n = 305)	N/A^b
Pediatric asthma % status asthmaticus	48.6%	51.9%	44.6%	N/A^b

^a DRGs 190, 191, 192.

^b Pediatric inhaler to neb protocol implemented one year after adult protocol.