Patterns of analgesic adherence predict health care utilization among outpatients with cancer pain

Figures & data

Table 1 Baseline variables

Variable type	Variable	Range	n (%)	Mean (SD)
Sociodemographic	Age, years (n=191)	23–75		53.8 (11.2)
	Education (n=191)	Elementary	3 (1.6)
		High school	62 (32.5)
		College/trade school	94 (49.2)
		More than college	32 (16.7)
	Employment status (n=191)	Employed full-time outside the home	40 (20.9)
		Employed part-time outside the home	11 (5.8)
		Employed full-time in the home	4 (2.1)
		Employed part-time in the home	4 (2.1)
		Retired	41 (21.5)
		Unemployed	24 (12.6)
		Other	67 (35.1)
	Health literacy, (n=191)	3–15		13.1 (2.6)
	Income, US$ (n=191)	<10,000	26 (13.6)
		10,000–20,000	24 (12.6)
		>20,000–30,000	18 (9.4)
		>30,000–50,000	31 (16.2)
		>50,000–70,000	34 (17.8)
		>70,000–90,000	23 (12.0)
		>90,000	35 (18.3)
	Primary insurance (n=190)	Private	99 (52.1)
		Medicare	37 (19.5)
		Medicaid	24 (12.6)
		Multiple	24 (12.6)
		VA/other	6 (3.2)
	Marital status (n=191)	Married	103 (53.9)
		Separated	14 (7.3)
		Divorced	28 (14.7)
		Widowed	8 (4.2)
		Never married	38 (19.9)
	Race (n=191)	Black/African-American	79 (41.4)
		White	112 (58.6)
	Social support, (n=191)	0.17–9.00		3.7 (2.1)
	Social support satisfaction (n=191)	1–6 (very dissatisfied–very satisfied)		5.6 (0.8)
Illness	Cancer stage (n=191)	I	20 (10.5)
		II	28 (14.7)
		III	34 (17.8)
		IV	60 (31.4)
		Unknown or unsure	49 (25.7)
	Time since cancer diagnosis, months (n=191)	1–120		37.4 (35.8)
	Charlson Comorbidity Index (n=191)	0–13		4.3 (2.7)
	General health (n=191)	Excellent	9 (4.7)
		Very good	23 (12.0)
		Good	58 (30.4)
		Fair	68 (35.6)
		Poor	33 (17.3)
	Physical health not good, days within last 30 (n=191)	0–30		14.6 (10.7)
	Mental health not good, days within last 30 (n=191)	0–30		9.6 (10.8)
	Past history of substance abuse (n=191)	No	157 (82.2)
		Yes	34 (17.8)
	Presence of chronic kidney disease (n=191)	No	103 (53.9)
		Yes	88 (46.1)
	Presence of depression (n=191)	No	110 (57.6)
		Yes	81 (42.4)
Pain, function, and pain treatment	Duration of cancer pain, months (n=175)	0–120	29.9 (31.0)
	Worst pain in last week (n=191)	0–10 (no pain–pain as bad as you can imagine)	6.8 (2.4)
	Average pain in last week (n=191)	0–10 (no pain–pain as bad as you can imagine)	4.9 (2.0)
	Least pain in last week (n=191)	0–10 (no pain–pain as bad as you can imagine)	3.3 (1.9)
	Pain-related functional interference score (n=191)	0–70 (does not interfere–completely interferes)	34.6 (15.8)
	Pain relief with medications (n=191)	1–10 (10%–100%)	7.3 (2.0)
	Hours pain medications effective (n=191)	Does not help at all	1 (0.5)
		1	6 (3.1)
		2	15 (7.9)
		3	27 (14.1)
		4	48 (25.1)
		5	82 (42.9)
		>12	12 (6.3)
	Pain Management Index (n=191)	−2	4 (2.1)
		−1	12 (6.3)
		0	83 (43.5)
		1	61 (14.7)
		2	28 (14.7)
		3	3 (1.6)
	Total number of analgesics prescribed (n=191)	1	41 (21.5)
		2	103 (54.9)
		3	36 (18.9)
		4	11 (5.8)
	Total number of coanalgesics prescribed (n=191)	0	149 (78.0)
		1	35 (18.3)
		2	7 (3.7)
	WHO analgesic step, index medication (n=191)	Step 1	18 (9.4)
		Step 2	20 (10.5)
		Step 3	153 (80.1)
	Prescription of long-acting opioids (n=191)	No	82 (42.9)
		Yes	109 (57.1)
	How often prescribed medication taken per day (n=191)	Not every day	2 (1.0)
		1–2 times	71 (37.2)
		3–4 times	81 (42.4)
		5–6 times	29 (15.2)
		>6 times	8 (4.2)
	Number of analgesic side effects, MSEC (n=191)	0–8		3.9 (2.4)
	Severity of side effects, MSEC (n=191)	8–80 (not severe–extremely severe)		25.5 (15.9)
	Number of complementary alternative modalities used (n=191)	0–8		2.1 (1.7)
Analgesic attitudes and barriers	CBC type of analgesic (n=191)	≤25%	155 (81.2)
		>25% and ≤50%	17 (8.9)
		>50% and ≤75%	19 (9.9)
	CBC pain relief with analgesics (n=191)	≤25%	83 (43.5)
		>25% and ≤50%	67 (35.1)
		>50% and ≤75%	41 (21.5)
	CBC type of side effects (n=191)	≤25%	145 (75.9)
		>25% and ≤50%	43 (22.5)
		>50% and ≤75%	3 (1.6)
	CBC severity of side effects (n=191)	≤25%	132 (69.1)
		>25% and ≤50%	41 (21.5)
		>50% and ≤75%	18 (9.4)
	CBC out-of-pocket cost of analgesics (n=191)	≤25%	180 (94.2)
		>25% and ≤50%	10 (5.2)
		>50% and ≤75%	1 (0.5)
	Analgesic barriers, BQ-II (n=191)	0–96		66.2 (20.2)
	BQ-II physiological effect severity (n=191)	0–51		30.6 (11.1)
	BQ-II fatalism severity (n=191)	0–15		6.2 (3.5)
	BQ-II communication severity (n=191)	0–28		11.3 (5.2)
	BQ-II harmful effects severity (n=191)	0–30		18.1 (7.3)
Subjective adherence	I sometimes forget to take my pain medicine, MMAS (n=191)	No	127 (66.5)
		Yes	64 (33.5)
	I am sometimes careless about taking my pain medicine (n=191)	No	158 (82.7)
		Yes	33 (17.3)
	When I feel better, I sometimes stop taking my pain medicine (n=191)	No	104 (54.5)
		Yes	87 (45.5)
	If I feel worse when I take the pain medicine, sometimes I stop taking it (n=191)	No	165 (86.4)
		Yes	26 (13.6)

Abbreviations: BQ, Barriers Questionnaire; CBC, choice-based conjoint analysis; MMAS, Morisky Medication Adherence Scale; MSEC, Medication Side-Effects Checklist; SD, standard deviation; VA, Veterans Administration; WHO, World Health Organization.

Figure 1 Adherence patterns for selected patients, including observed cap opening rates per day per dose, fitted mean adherence curve, and lower and upper unit error-bound curves.

Figure 2 Plots of mean adherence and adherence-variability centroids for adherence types.

Table 2 Description of adherence types

Cluster	n (%)	Adherence types		Average dose adherence
		Mean adherence	Adherence variability
1	46 (24.0)	High	Low to moderately low	96.1
2	32 (16.7)	High to moderately high	Low to moderate	85.3
3	34 (17.7)	High to moderately high	Moderate	82.4
4	31 (16.1)	Moderate	Moderately low	39.1
5	19 (9.9)	Low	Low	11.2
6	30 (15.6)	Moderately high to low	Very high to very low	43.0
Total	191 (100)

Table 3 Individually significant risk factors for hospitalization

Variable type	Variable	Risk factora	At-risk group, n (%)	P-valueb	OR	95% CIb
Sociodemographic	Age, years	≤50 vs >50	65 (34.0)	0.040	2.25	1.04–4.85
	Employment status	Employed at home part-time, unemployed, or other vs employed outside home full- or part-time, employed at home full-time, or retired	95 (49.7)	0.003	3.72	1.58–8.78
	Health literacy	≤12 vs >12	55 (28.8)	0.016	2.63	1.20–5.73
	Primary insurance	Medicaid, other, VA, none, or multiple vs private, Medicare, or missing	137 (71.7)	0.036	2.31	1.06–5.07
	Social support	≤4.67 vs >4.67	141 (73.8)	0.026	4.06	1.18–14.0
Illness	General health	Poor vs better	33 (17.3)	0.026	2.69	1.13–6.41
Pain, function, and pain treatment	Worst pain (last week)	≤5 vs >5	50 (26.2)	0.045	2.26	1.02–5.00
	WHO analgesic step (index medication)	Strong opioid vs nonopioids or weak opioids	153 (80.1)	0.050	4.39	1.00–19.3
	Severity of analgesic side effects	≥15 vs <15	137 (71.7)	0.038	3.21	1.07–9.65
Analgesic attitudes and barriers	BQ-II item: weakens immune system	≥3 vs <3	50 (26.2)	0.001	3.68	1.67–8.10
	BQ-II item: confusion from pain medicine cannot be controlled	≥3 vs <3	32 (16.8)	0.019	2.83	1.18–6.77
	BQ-II item: body becomes used to effects	≥1 vs <1	145 (75.9)	0.044	3.58	1.04–12.4
	BQ-II item: can harm immune system	≥3 vs <3	44 (23.0)	0.012	2.83	1.26–6.33
	BQ-II item: makes you say or do embarrassing things	≥1 vs <1	80 (41.9)	0.012	2.75	1.26–6.02
	BQ-II item: if doctors have to deal with pain, they won’t concentrate on curing the disease	≥1 vs <1	44 (23.0)	0.003	3.34	1.50–7.47
	BQ-II item: can harm immune system	≥3 vs <3	41 (21.5)	0.001	3.80	1.69–8.56
	BQ-II item: won’t work as well if you need it later	≥3 vs <3	64 (33.5)	0.033	2.31	1.0–5.00
	BQ-II: physiological effect severity	≥41 vs <41	40 (20.9)	0.045	2.35	1.02–5.40
	BQ-II: harmful effect severity	≥20 vs <20	77 (40.3)	0.018	2.55	1.17–5.53
Subjective adherence	Analgesic adherence typec	Inconsistent (clusters 1–5) vs consistent (cluster 1)	146 (76.4)	<0.001	4,630	2,839–7,549
	Dose adherence	≤84.2% vs >84.2%	115 (60.2)	0.027	2.74	1.12–6.70

Notes:

a Reference category follows “vs”;

b based on standard Wald χ² tests, except where otherwise indicated;

c P-values based on robust empirical Wald z-tests. ORs and CIs are very large because no patients without the risk factor were hospitalized.

Abbreviations: BQ, Barriers Questionnaire; CI, confidence interval; OR, odds ratio; VA, Veterans Administration; WHO, World Health Organization.

Table 4 Multiple risk-factor model for hospitalization

Variable type	Variable	Risk factora	At-risk group, n (%)	P-valueb	OR	95% CIb
Sociodemographic	Age, years	≤50 vs >50	65 (34.0)	0.002	4.51	1.74–11.6
	Health literacy	≤12 vs >12	55 (28.8)	0.003	4.40	1.67–11.6
Illness	–
Pain, function, and pain treatment	WHO analgesic step (index medication)	Strong opioid vs nonopioids or weak opioids	153 (80.1)	0.009	7.81	1.67–36.6
Analgesic attitudes and barriers	BQ-II item: can harm your immune system	≤3 vs <3	44 (23.0)	0.002	4.79	1.79–12.8
Objective analgesic adherence	Analgesic adherence typec	Inconsistent vs consistent	146 (76.4)	<0.001	17,049	9,557–30,414

Notes:

a Reference category follows “vs”;

b based on robust empirical Wald z-tests;

c ORs and CIs are very large because no patients without the risk factor were hospitalized.

Abbreviations: BQ, Barriers Questionnaire; CI, confidence interval; OR, odds ratio; WHO, World Health Organization.

Table 5 Multiple pairwise risk-factor interaction model for hospitalization

Interaction term 1		Interaction term 2		At-risk group, n (%)	P-valueb	OR	95% CIb
Variable	Risk factora	Variable	Risk factora
WHO analgesic step (index medication)	Strong opioid vs nonopioids or weak opioids	Adherence adherence type	Inconsistent vs consistent	111 (58.1)	0.001	16.50	3.17–85.7
Employment status	Employed at home part-time, unemployed, or other vs employed outside home full- or part-time, employed at home full-time, or retired	BQ-II item: if doctors have to deal with pain, they won’t concentrate on curing the disease	≥1 vs <1	44 (23.0)	0.006	5.06	1.59–16.1
Social support	≤4.67 vs >4.67	BQ-II item: can harm immune system	≥3 vs <3	41 (21.5)	0.010	4.09	1.40–12.0
Insurance type	Medicaid, other, VA, none, or multiple vs private, Medicare, or missing	BQ-II item: makes you say or do embarrassing things	≥1 vs <1	80 (41.9)	0.003	8.04	2.03–31.9
Age, years	≤50 vs >50	Severity of analgesic side effects	≥15 vs <15	50 (26.2)	0.009	4.23	1.43–12.5
Health literacy	≤12 vs >12	Severity of analgesic side effects	≥15 vs <15	46 (24.1)	0.016	3.84	1.29–11.4

Notes:

a Reference category follows “vs”;

b based on standard Wald χ² tests.

Abbreviations: BQ, Barriers Questionnaire; CI, confidence interval; OR, odds ratio; VA, Veterans Administration; WHO, World Health Organization.

Table 6 Individually significant risk factors for inconsistent adherence

Variable type	Variable	Risk factora	At-risk group, n (%)	P-valueb	OR	95% CIb
Sociodemographic	Age, years	≤61 vs >61	139 (72.8)	0.004	2.85	1.41–5.78
	Education	College, trade school, or less vs more than college	159 (83.2)	0.045	2.29	1.02–5.16
	Income, US$	≤$50,000 vs >$50,000	99 (51.8)	0.014	2.39	1.19–4.77
	Race	Black vs white	79 (41.4)	0.004	3.14	1.45–6.80
Illness	Time since cancer diagnosis, months	≤66 vs >66	150 (78.5)	0.010	2.67	1.27–5.64
	Physical health not good, days within last 30	≤29 vs 30	152 (79.6)	0.045	2.19	1.02–4.69
Pain, function, and pain treatment	Duration of cancer pain, months	≤31 vs >31 or missing	122 (63.9)	0.018	2.27	1.15–4.49
	WHO analgesic step (index medication)	Nonopioids or weak opioids vs strong opioid	38 (19.9)	0.018	4.41	1.29–15.1
	Prescription of long- acting opioids	No vs yes	82 (42.9)	0.002	3.41	1.57–7.39
Analgesic attitudes and barriers	BQ-II item: body becomes used to effects	5 vs <5	40 (20.9)	0.030	3.36	1.12–10.0
	BQ-II item: very addictive	5 vs <5	48 (25.1)	0.042	2.63	1.03–6.66

Notes:

a Reference category follows “vs”;

b based on standard Wald χ² tests.

Abbreviations: BQ, Barriers Questionnaire; CI, confidence interval; OR, odds ratio; WHO, World Health Organization.

Table 7 Multiple risk-factor model for inconsistent adherence

Variable type	Variable	Risk factora	At-risk group, n (%)	P-valueb	OR	95% CIb
Sociodemographic	Age, years	≤61 vs >61	139 (72.8)	0.003	3.38	1.54–7.45
Illness	–
Pain, function, and pain treatment	Prescribed long-acting opioids	No vs yes	82 (42.9)	0.005	2.83	1.36–5.87
Analgesic attitudes and preferences	–

Notes:

a Reference category follows “vs”;

b based on standard Wald χ² tests.

Abbreviations: BQ, Barriers Questionnaire; CI, confidence interval; OR, odds ratio.

Table 8 Multiple risk-factor and pairwise interaction model for inconsistent adherence

Interaction term 1		Interaction term 2		At-risk group, n (%)	P-valueb	OR	95% CIb
Variable	Risk factora	Variable	Risk factora
Duration of cancer pain	≤31 vs >31 or missing	BQ-II item: very addictive	5 vs <5	25 (13.1)	<0.001	7,298c	3,829–13,912c
Income, US$	≤50,000 vs >50,000	Physical health not good, days within last 30	≤29 vs 30	85 (44.5)	0.009	2.88	1.31–6.33
Education	College, trade school, or less vs more than college	Age, years	≤61 vs >61	55 (28.8)	0.009	2.66	1.27–5.54
WHO analgesic step (index medication)d	Nonopioids or weak opioids vs strong opioid	–	–	38 (19.9)	0.031	4.11	1.13–14.9

Notes:

a Reference category follows “vs”;

b based on robust empirical Wald z-tests;

c OR and CI very large because all patients without the risk-factor interaction had consistent adherence;

d a non-interaction risk factor.

Abbreviations: CI, confidence interval; OR, odds ratio; BQ, Barriers Questionnaire; WHO, World Health Organization.