A systematic literature review of the clinical and health economic burden of schizophrenia in privately insured patients in the United States

Figures & data

Figure 1 PRISMA flowchart depicting search strategy and outcomes of the systematic literature review.

Abbreviation: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Table 1 Patient characteristics

Study	No. of patients commercially insured (%)a	Age (mean) (years)	Sex (%)	US regionb
Carney et al^Citation13	1,074 (100)	40.2	M: 47.0; F: 53.0	Iowa residents only
Cloutier et al^Citation11	31,698 (29.6)	N/A	N/A	Nationally representative
Dodds et al^Citation25	18 (37.5)	22.2	M: 89.6; F: 10.4	Connecticut residents only
Fisher et al^Citation20	4,156 (100)	40	M: 53.1; F: 46.9	Nationally representative
Fitch et al^Citation26	8,985 (100)	N/A	N/A	Nationally representative
Gianfrancesco et al^Citation31	3,807 (100)	41.2	M: 38.8; F: 61.2	Nationally representative
Gibson et al^Citation15	1,392 (17.6)	42.8	M: 38.0; F: 62.0	Northeast: 8.6% North Central: 33.0% South: 36.4% West: 21.6% Unknown region: 0.4%
Haynes et al^Citation12	94 (4.1)	41.8	M: 61.6; F: 38.4	California, Colorado, Connecticut, Florida, Maryland, and North Carolina
Joshi et al^Citation16	2,713 (100)	40.2	M: 47.3; F: 52.7	Midwest: 29.0% Northeast: 13.5% South: 44.1% West: 13.4%
Khaykin et al^Citation6	42 (12.3)	N/A	M: 58.3; F: 41.7	Northeast: 8.6% Midwest: 26.4% South: 35.0% West: 30.0%
Kim et al^Citation17	84 (23.9)	43.4	M: 44.4; F: 55.6	N/A
Lafeuille et al^Citation27	386 (3.5)	LAI: 42.1 Oral: 42.4	LAI vs. oral M: 56.4 vs. 55.4 F: 43.6 vs. 44.6	South: 41.2% Midwest: 25.1% West: 17.6% Northeast: 16.1%
Lang et al^Citation7	7,528 (26.7)	47.9	M: 47.0; F: 53	N/A
Lin et al^Citation10	3,004 (81.9)	LAI: 41.7	LAI vs. oral	LAI vs. oral
Offord et al^Citation18		Oral: 37.1	M: 51.8 vs. 50.3 F: 48.2 vs. 49.7	Northeast: 11.2% vs. 11.3% North Central: 47.0% vs. 29.5% South: 32.0% vs. 33.5% West: 9.4% vs. 24.9%
McCombs et al^Citation23	5,909 (100)	41.3	M: 37.6; F: 62.4	N/A
Nicholl et al^Citation14	3,187 (80.4)	Recently diagnosed patients: 28.1 Chronic patients: 45.4	Recently diagnosed vs. chronic M: 56.7 vs. 48.2 F: 43.3 vs. 51.8	Recently diagnosed vs. chronic Northeast: 20.8% vs. 24.4% Midwest: 56.9% vs. 54.6% South: 10.9% vs. 10.5% West: 11.3% vs. 10.6%
Offord et al^Citation2	1,462 (100)	Nonadherent: 38.6 Adherent: 39.9	N/A	Nonadherent vs. adherent Northeast: 11.2% vs. 10.2% North Central: 31.6% vs. 34.3% South: 36.9% vs. 31.1% West: 19.6% vs. 23.6% Unknown: 0.7% vs. 0.9%
Panish et al^Citation28	562 (100)	43.5	M: 37.7; F: 62.3	New England: 2.5% Mid-Atlantic: 4.8% East North Central: 7.8% West North Central: 15.1% South Atlantic: 36.5% East South Central: 3.9% West South Central: 16.0% Mountain: 9.8% Pacific: 3.6%
Pyenson et al^Citation19	4,665 (50.3)	39.4	M: 50; F: 50	N/A
Peng et al^Citation24	147 (100)	42.6	M: 53.7; F: 46.3	N/A
Rost et al^Citation22	N/A 3,359 outpatient visits	N/A	M: 54.1; F: 45.9	Northeast: 33.0% Midwest: 16.9% South: 29.6% West: 20.5%
Stensland et al^Citation29	N/A Only numbers of psychiatric hospitalizations available	N/A	N/A	N/A
Wang and Farley^30c	1.89 million	N/A	M: 49 vs. F: 51	Atypical AP vs. typical AP Northeast: 24.08% vs. 30.33% Midwest: 23.51% vs. 23.66% South: 34.34% vs. 25.76% West: 18.08% vs. 20.26%
Wilson et al^Citation21	414	36.5	M: 49.4; F: 50.6	California

Notes:

a The percentage represents the share of commercially insured patient population that accounts for the total study population.

b Some percentages do not sum to 100 because of rounding.

c Patients were not included in health resource utilization calculations.

Abbreviations: AP, antipsychotic; F, female; LAI, long-acting injectable AP; M, male; N/A, not available.

Table 2 Medication adherence

Study	Adherence index	Patient subpopulation of interest	AP adherence
Haynes et al^Citation12	SCAP-HQa	Nonremitted vs. remitted cohort	SCAP-HQ nonadherent: Baseline: 1.48 vs. 1.36 1 year: 1.43 vs. 1.33 2 years: 1.39 vs. 1.30 3 years 1.3 vs. 1.30
Joshi et al^Citation16	MPR PDC	Incident schizoaffective disorder vs. prevalent schizoaffective disorder	MPR ≥ 80%: 44.9% vs. 58.7% (p < 0.001) PDC ≥ 80%: 33.6% vs. 48.5% (p < 0.001)
Kim et al^Citation17	MMASb	With (vs. without) copayment burden	Adherence (MMAS < 2): 58.4% vs. 68.7% (p = 0.049) Complete adherence (MMAS = 0): 28.5% vs. 46.7% (p = 0.001)c
Lang et al^Citation7	MPR Maximum continuous gap in treatment	N/A	Percentage with MPR < 80%: 44.6% Maximum continuous gap in treatment (days): 38.8
Offord et al^Citation2	MPR	Early nonadherent (vs. early adherent) cohort	MPR: 0.22 vs. 0.73 (p < 0.0001)
Offord et al^Citation18	MPR	LAI (vs. oral AP) users	MPR: 0.67 vs. 0.56 (p < 0.001)
Pyenson et al^Citation19	Compliance rated	No subpopulation of interest	Average compliance rate: 61.0%

Notes:

a Scores ranged from 1 to 5, with higher scores indicating worse medication adherence, by patient ratings.

b The MMAS consists of four yes/no questions that assess adherence to prescribed medication. These questions assess forgetfulness about taking medication, carelessness about taking medication, stopping medication when feeling better, and stopping medication when feeling worse. The score is the sum of “yes” responses, with a range of 0–4. A score of ≥2 is associated with a high likelihood of medication nonadherence. Throughout the analyses, respondents with a score of ≥2 were classified as nonadherent and those with a score of 0 or 1 were classified as adherent. In addition, complete adherence was defined as a score of zero.

c All significant p-value comparisons are indicated.

d $\text{Compliance rate}=\frac{\text{Days’ supply of SGAs in a year}}{\text{Days of insurance coverage}}$.

Abbreviations: AP, antipsychotic; LAI, long-acting injectable AP; MMAS, Morisky Medication Adherence Scale; MPR, medication possession ratio; PDC, proportion of days covered; SCAP-HQ, Schizophrenia Care and Assessment Program Health Questionnaire; N/A, not applicable; SGA, second-generation AP.

Table 3 Health resource utilization (HRU) and costs for privately insured US patients with schizophrenia: comparisons across all studies

Study	Data source	Time frame	Patient subpopulation of interest	All-cause HRU and costs
				Hospitalization	ED visit	Costs
Cloutier et al^Citation11	Truven MarketScan Commercial Claims Database	2013	Patients with schizophrenia	N/A	N/A	Per-capita costs: Medication = $3,500 Outpatient = $2,468 Inpatient = $5,160 ED = $871 Other medical = $281 Total = $12,461a
Fitch et al^Citation26	Truven MarketScan Commercial Claims Database	2007–2011	Patients with (vs. without) SCZ	Annual inpatient admissions per 1,000 patients: 636 vs. 48	Annual ED visits per 1,000 patients: 2,270 vs. 158	Mean cost PPPM: Inpatient cost: $762 vs. $97 Outpatient cost: $592 vs. $239 Prescription drug cost: $452 vs. $83
Offord et al^Citation18	Truven MarketScan Commercial Claims Database	January 1, 2005–September 30, 2010	LAI vs. oral AP	Mean difference in the number of hospitalizations: –0.90 ± 1.77 vs. 0.02 ± 1.49 Mean difference in the total LOS (days): –10.3 ± 23.2 vs. 0.7 ± 16.7 days	N/A	N/A
Early nonadherent vs. early adherent
Offord et al^Citation2	Truven MarketScan Commercial Claims Database	January 1, 2006 to September 30, 2009	Early nonadherent (vs. early adherent) to oral APs	Number of hospitalizations, mean ± SD: 0.57 ± 1.08 vs. 0.38 ± 0.90 Total LOS (days in hospital), mean ± SD: 5.0 ± 13.6 vs. 3.0 ± 8.6	N/A	All-cause hospitalization cost: $5,850 vs. $4,211 (p = 0.024) SCZ-related hospitalization cost: $2,952 vs. $1,969 (p = 0.0465) Total annual per-capita cost $5,358 vs. $6,660 (p = 0.021) Total annual pharmacy per- capita cost: $1,549 vs. $3,684 (p < 0.0001)
Nicholl et al^Citation14	PharMetrics Integrated Database	1998–2007	Recently diagnosed patients vs. chronic patients	% hospitalized: 22.3% vs. 12.4% (p < 0.0001) Mean number of days in hospital: 5.1 vs. 3.0 (p = 0.0065)	% of patients: 24.6% vs. 17.5% (p < 0.0001) Mean number of admissions: 0.48 vs. 0.36 (p = 0.0019)	Total mean annual per-capita health care cost: $20,654 vs. $15,489 (p < 0.0001)
Peng et al^Citation24	Thomson Medstat MarketScan Commercial Claims and Encounters databases	January 1, 2004–March 31, 2008	6-month pre- vs. 6-month post- depot initiation	Proportion hospitalized for any reason: 53.7% vs. 29.9% Days hospitalized for any reason, mean: 8.0 vs. 5.3	N/A	Total per-capita health care costs: $7,884 after LAI vs. $11,111 before LAI (p < 0.05) Psychiatric hospitalization costs: $2,538 after LAI vs. $5,384 before LAI (p < 0.05)
Wilson et al^Citation21	Claims database analysis of a private insurer	June 2001–May 2004	Newly diagnosed patients vs. previously diagnosed patients	N/A	N/A	Total: $15,282 vs. $12,029 (p = 0.09) Total inpatient services: $7,745 vs. $4,440 (p = 0.03) Total prescriptions: $3,165 vs. $4,548 (p = 0.002)

Note:

a All costs not included in total.

Abbreviations: AP, antipsychotic; ED, emergency department; LAI, long-acting injectable AP; LOS, length of stay; N/A, not available or not applicable; PPPM, per patient per month; SCZ, schizophrenia.

Table S1 Search terms and outcomes

Index	Description	Search terms
1	Patients	schiz* AND (“insurance” OR “insured” OR “commercially insured” OR “privately insured” OR “employer sponsored insurance” OR “beneficiary” OR “beneficiaries” OR “hmo” OR “ppo” OR “epo” OR “pos” OR “hdhp” OR “truven” OR “claim database” OR “ims” OR “United Health Care” OR “uhc” OR “kaiser*” OR “magellan” OR “blue cross blue shield” OR “WellPoint” OR “wellcare” OR “Aetna” OR “Cigna” OR “Highmark” OR “hcsc”)
	Patients (subgroup: early diagnosis)	“early diagnos*” OR “early” OR “newly diagnos*” OR “first episode”
	Patients (subgroup:adolescents and young adults)	“adolescent* OR “young”
2	Treatment	“antipsychotic” OR “antipsychotics” OR “depot” OR “LAI” OR “long-acting” OR “injectable” OR “oral medication”
3	Clinical burden	“relapse” OR “hospitalization” OR “hospital*” OR “admission*” OR “emergency” OR “er” OR “functioning” OR “cognition” OR “brief psychiatric rating scale” OR “bprs” OR “positive and negative syndrome scale” OR “panss” OR “clinical global impression” OR “cgi” OR “personal and social performance” OR “psp” OR “short form (36) health survey” OR “sf-36” OR “global assessment of functioning (gaf) scale” OR “gaf” OR “quality of life” OR “qol” OR “treatment satisfaction” OR “comorbid” OR “comorbidity” OR “comorbidities” OR “remission” OR “remit” OR “outpatient” OR “inpatient” OR “discontinuation” OR “adherence”
4	Economic burden	“relapse” OR “hospitalization” OR “Financial burden” OR “burden” OR “Economic*” OR “cost of illness” OR “cost” OR “finance” OR “financial” OR “resource” OR “utilization” OR “budget” OR “expenditure” OR “expense” OR “money” OR “spending” OR “price” OR “Indirect work loss” OR “absenteeism” OR “Presenteeism” OR “work productivity” OR “work loss” OR “activity impairment”
5	Patient adherence	“adherence” OR “nonadherence” OR “non-adherence” OR “adherent” OR “nonadherent” OR “compliance” OR “non-compliance” OR “noncompliance” OR “compliant” OR “non-compliant” OR “concordance” OR “non-concordance” OR “medication concordance” OR “persistence” OR “non-persistence” OR “nonpersistence” OR “persistent” OR “nonpersistent” OR “Proportion of Days Covered” OR “Continuous Measure of Medication Acquisition” OR “Continuous Multiple Interval Measure of Oversupply” OR “Medication Possession Ratio” OR “Medication Refill Adherence” OR “Continuous Measure of Medication Gaps” OR “Continuous, Single Interval Measure of Medication Acquisition” OR “Proportion of Days Covered” OR “Refill Compliance Rate” OR “Medication Possession Ratio, modified” OR “Dates Between Fills Adherence Rate” OR “Compliance Rate”
6	Publication type	“Journal Article” OR “Review”
7	Publication time period	2006–2016
Combined search strategies
8	Patient + treatment + publication type + year + English only	(1) + (2) + (6) + (7) + English only
9	Patient + clinical burden + publication type + year + English only	(1) + (3) + (5) + (6) + (7) + English only
10	Patient + economic burden + publication type + year + English only	(1) + (4) + (6) + (7) + English only

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