Table 1.

Studies examining the impact of co-payment, tiering or coinsurance on prescription drug utilization and spending, medical utilization and spending (65 studies)

Author	Study sample	Study design	Drug benefit variation	Outcomes	Key findings
Studies that examine the impact on prescription drug utilization only
Andersson K et al., 2006	Delivers of pharmaceuticals to the Swedish population from Jan 1986 to Dec 2002, at the chemical subgroups level ( Aggregated data from National Corporation of Swedish Pharmacies )	Time series	Three national policies (Jan 1, 1991; Jan 1, 1995 and January 1, 1999) in Sweden increasing patient drug co-payment	Total defined daily doses (DDDs) Total drug costs	Co-payment increases were not associated with changed level or slope of drug cost or volume
Dormuth CR, 2006	173,076 elderly patients with COPD or asthma in British Columbia (Pharmacy claims and administrative medical records 1997–2004)	Before-after no control group	Drug policies in three periods for BC elderly on patients’ prescription payment: 1) 100% dispensing fee up to an annual ceiling of Can $200 (before 2002); 2) $10 or $25 drug co-payment with annual ceilings of $200 or $275, depending on income (Jan 2002-Apr 2003); 3) 25% coinsurance + income based deductible + revised income-based annual ceilings(Since May 2003)	DDDs per 10,000 patient months Drug initiation and cessation	Drug policy changes in 2002–2003 for BC elderly were associated with significant reductions in the use of inhaled medications (−12.3% to −5.8%), Newly diagnosed patients were 25% less likely to initiate treatment in period 2) or 3), compared to period 1). Chronic users were 47% and 22% more likely to cease treatment during period 2) and 3), compared to period 1).
Gibson TB et al., 2006	234,685 statin users continuously enrolled in a health plan during 2001–2003 (Enrollment data, pharmacy and medical claims 2001 – 2003)	Longitudinal	Variation in statin co-payments across health plans and over time	MPR	A 100% co-payment increase lowered monthly adherence rates for statin medications by 2.6 and 1.1 percentage points among new and continuing users, respectively. Those who recently initiated satins therapy were more price-sensitive.
Goldman DP et al., 2006	62,774 adults continuously enrolled in a health plan for at least 1 year before and after initiating cholesterol therapy (Pharmacy claims and medical claims data 1997–2002)	Repeated cross-sectional	Variation in statin co-payments across health plans	MPR	A 100% co-payment increase lowered the fraction of fully compliant patients for cholesterol therapies by 10 to 6 percentage points, depending on patient risk. Eliminating co-payments for high- and medium- risk patients, while raising them (from $10 to $22) for low-risk patients is predicted to avert 79,837 hospitalizations and 31,411 ED visits annually among a national sample of 6.3 million adults on CL therapy.
Goldman DP et al., 2006	Patients with at lest two primary diagnoses for cancer, kidney disease, Rheumatoid Arthritis(RA) or Multiple Sclerosis(MS) among 1.5 million private insurance enrollees. (Pharmacy claims and medical claims data 2003–2004)	Repeated Cross-sectional	Variation in drug coverage generosity (ratio of total out-of-pocket payments relative to total payments, for a specific drug category) across health plans and over time (2003–2004)	Rx spending	A 100% increase in effective coinsurance rate was associated with 7% decrease in MS total drug spending and 21% decrease in RA drug spending. The spending reductions for cancer drugs and Kidney disease drugs were smaller: 1% and 11% respectively and were not statistically significant.
Li X et al., 2006	8,017 elderly British Columbia residents with rheumatoid arthritis (Administrative data 2001–2002)	Before-after no control group	Drug policy changes for BC elderly on patients’ prescription payment: 1) 100% dispensing fee up to annual ceilings of Can $200 (before 2002); 2) $10 or $25 drug co-payment with annual ceilings of $200 or $275, depending on income (Jan 2002-Apr 2003)	Number of prescriptions filled Physician visits	100% increase in effective drug price (the price an individual would face under the new cost-sharing policy if their consumption remained at the pre-policy level) was associated with 20% to 11% reduction in drug use, and 4% to 6% increase in physician visits, for low-income seniors and other seniors, respectively.
Taira DA et al., 2006	114,232 hypertension patients who filled prescriptions for hypertensive medications between Jan 1999 to June 2004 (Administrative data and pharmacy claims data from a MCO 1999–2004)	Repeated cross-sectional	Three co-payment levels in a tiered formulary: $5, $20, and $20–165	Adherence (MPR >= 0.8)	Relative to medications with a $5 co-payment, the odds ratio for compliance with drugs having a $20 co-payment was 0.76; for drugs requiring a $20 to $165 co-payment, the odds ratio for compliance was 0.48.
Wang J et al., 2006	47,115 adult prescription users in Medical Expenditures Panel Survey (MEPS) 1996–2001	Repeated cross-sectional	Cross-sectional variation in generosity of drug benefit (share of annual drug cost paid by insurance)	Number of filled prescriptions	Non-Hispanic blacks were less likely than non-Hispanic whites to receive essential new drugs. The number of essential new drugs acquired is negatively correlated with co-payments.
Anis AH, et al., 2005	2,968 elderly British Columbia residents with rheumatoid arthritis (Pharmacy claims data and administrative medical records 1996–2000)	Before-after no control group	Periods before and after annual drug co-payments reached the maximum, within a calendar year	Number of filled prescriptions Hospital admissions	Among elderly patients with rheumatoid arthritis and who had exceeded the maximum annual co-payment of Can $200 at least once during the period of 1997–2000, there were 0.38 more physician visits per month, 0.50 fewer prescriptions filled per month and 0.52 fewer prescriptions filled per physician visit, during the “cost-sharing” period, compared to the “free” period. Frequency of hospital admissions didn’t differ.
Contoyannis P et al., 2005	573, 426 elderly randomly selected from the population of Quebec Pharmacare beneficiaries from Aug 1993 – June 1997 (Administrative data 1993 – 1997)	Before-after no control group	Two drug policy changes in Quebec Pharmacare program: Before Aug 1996, low-income elderly had free drug coverage while other elderly paid $2 per prescription. Since Aug 1996 all paid %25 coinsurance with income-based annual ceilings. Beginning Jan 1997 a quarterly deductible was added and an annual ceiling was applied per quarter and still varied by income.	Rx spending	A 100% increase in effective drug price (the price an individual would face under the new cost-sharing policy if their consumption remained at the pre-policy level) was associated with 16% to %12% reduction in total drug spending in a given period.
Gibson TB et al., 2005	114,232 employees in two firms (Pharmacy claims and medical claims 1995–1998)	Before–after with a control group	Co-payment level in one firm changed from $2 to $2, $7 for generics and brand-name drugs, respectively; co-payment level in the other firm remained unchanged	Number of filled prescriptions Rx spending	A 100% co-payment increase in brand drugs was associated with a 4% decrease in total drug use, 27% decrease in the use of multi-source brand drugs and a 32% decrease in the use of single source brands. Total drug expenditures decreased by about 10%. Enrollees with a newly diagnosed chronic condition were less price-sensitive.
Hansen RA et al., 2005	9,819 privately insured PPI users in year 1998 (Administrative claims data 1997–1998, DTC advertising expenditure data)	Cross-sectional	Whether or not a plan has > $5 copay for a brand-name PPI prescription across multiple drug benefit plans	Rx switching	Patients paying >$5 copay for brand-name PPI prescription were 12% less likely to switch from lansoprazole to omeprazole than patients paying lower copayments.
Huskamp HA et al., 2005	36,102 children continuously enrolled for 33 months as dependents in two employer-sponsored managed care plans (Eligibility file and pharmacy claims data 1999–2001)	Before-after with control group	One employer changed formulary from 1-tier to 3-tier and increased co-payments in all tiers. The other employer had a stable 2-tier formulary	Initiation of drug therapy Discontinuation rate Rx spending OOP and plan Rx spending	Adding a third tier with a $30 co-payment decreased the probability that children received a drug for attention-deficit/hyperactivity disorder by 17%, decreased total medication spending by 20% and shifted more medication costs to patients.
Landsman PB et al., 2005	Users of nine drug classes continuously enrolled for two years in one of four managed care plans with total members of 1,630,000 (Enrollment and pharmacy claims data 1999–2001)	Before-after with control group	Three plans changed from 2-tier formulary to 3-tier formulary while one plan had a stable 2-tier formulary	MPR Discontinuation rate Rx switching Number of filled prescriptions	Patients had statistically significant decreases in MPRs in seven out of nine drug classes. A 100% co-payment increase lowered the number of monthly filled prescriptions in each of the nine drug classes. Reductions ranged from 60 percent to 10 percent.
Roblin DW et al., 2005	26,220 12-month episodes of oral hypoglycemic (OH) from 5 MCOs (Enrollment and pharmacy claims data 1997–1999)	Time series	Variations in over time co-payment increase ($0 to $10 or more) across 5 MCOs	Standard OH average daily dose (ADD) per month	>$10 co-payment increase decreased use of oral hypoglycemic (OH) medications by 18.5%. Smaller co-payment increases had no significant effect on OH spending.
Briesacher B et al., 2004	20,868 patients with arthritis, enrolled in 32 employer-sponsored drug plans and used NSAIDs during year 2000 (Pharmacy claims, medical claims and encounter data 2000)	Cross-sectional	Variation in drug tiers and co-payments for COX II selective inhibitors across drug plans	Probability of using COX II selective inhibitors	The odds of using COX II selective inhibitors were significantly lower (odds ratio 0.36) if their drug formulary designated COX II as only non-preferred products compared with patients with 1-tier drug coverage; Co-payments exceeding $15 were also associated with lower odds (0.49) of drug initiation, relative to co-payments of $5 or less. Such relationship persists even for patients who had GI comorbidities.
Crown WH et al., 2004	63,231 asthma patients with employer-sponsored drug plans (Pharmacy claims, medical claims and encounter data 1995–2000)	Repeated cross-sectional	Cross-sectional variations of drug co-payments	Initiation of Rx therapy Days of supply Controller-to-Reliever ratio of asthma drugs	The level of patient cost-sharing did not affect the use of asthma medications. However, physician/practice prescribing patterns strongly influenced patient-level treatment patterns.
Ellis JJ et al., 2004	4,802 non-Medicaid enrollees with statin prescriptions in one MCO and between Jan 1998 to Nov 2001 (Pharmacy and medical claims 1998–2001)	Repeated cross-sectional	Cross-sectional variations of drug co-payments	Cumulative multiple refill-interval gap (CMG) Discontinuation rate	The mediums duration for statin therapy were 3.9 years, 2.2 years, and 1.0 years for patients whose average monthly statin co-payments were <$10, $10–20, and>$20, respectively.
Goldman DP et al., 2004	528,969 privately insured beneficiaries aged 18–64 and enrolled from 1 to 4 years in one of 52 health plans (Pharmacy and medical claims data 1997–2000)	Repeated cross-sectional	Cross-sectional variations of indexes of drug plan generosity	Days of supply	100% co-payment increase in a two-tier plan lowered utilizations in each of 8 therapeutic classes. Reductions range from 25% to 45%. Largest reductions were for drugs with close OTC substitutes.
Kamal-Bahl S et al., 2004	149,243 hypertension patients who had prescriptions for at least one of the five classes of drugs during year 1999 (Pharmacy claims, medical claims and encounter data 1999)	Cross-sectional	Cross-sectional variations in co-payments within 1, 2, or 3 tiered formularies	Initiation of drug therapy Rx spending OOP and plan Rx spending	Lower likelihood of using ACE inhibitors and angiotensin II receptor blockers with co-payment differences of at least $10 between generic and brand drugs. A 100% increases in drug-co-payment was associated with a predicted decrease of 8.9% in total drug spending in a 1-tier plan.
Liu SZ et al., 2004	More than 3 million prescriptions for a sample of elderly patients randomly drawn from 21 hospitals in Taipei (Administrative data 1998 – 2000)	Before-after with control group	Since Aug 1999, prescription drug policy in Taiwan changed from full coverage to 20% coinsurance with a maximum of $15.625 per prescription, for prescriptions costing more than $3.125. Selected groups were exempted	Average prescription cost	Compared to the non-cost sharing group, cost sharing group experienced a lower growth of average prescription cost since drug policy change. Elderly with non-chronic diseases were more price-sensitive.
Lurk JT et al., 2004	Aggregated monthly data Nov 1999 to Dec 2002 in one safety-net provider	Before-after no control group	Over-time change in drug co-payments	Number of filled prescriptions OOP and plan Rx spending	An average $5 increase in co-payment was associated with reduced drug utilization and a $26.07 decrease in prescription drug cost to the clinic per visit per month, in an ambulatory care safety-net provider setting.
Meissner BL et al., 2004	8,463 beneficiaries continuously enrolled in a public employer health plan from 1998–1999 (Pharmacy claims data 1998–1999)	Before-after no control group	Over-time change in drug co-payments	Days of supply Number of filled prescriptions Plan Rx spending	An average $10 co-payment increase for two classes of allergy medications was not associated with significant change in combined lower-sedating antihistamines (LSA) and nasal steroids (NS). In stead, it was associated with 13% reduction in plan drug cost for allergic rhinitis patients. Unadjusted Arc elasticity is 0.39 for LSA and −0.22 for NS.
Blais L et al., 2003	34,627 Quebec residents receiving social assistance, aged 64 or less and had any prescription for medications under study (Quebec Administrative claims data 1992–1997)	Time series	Drug policy changed for Quebec elderly in 1996–1997: from zero or $2 drug co-pay to %25 coinsurance plus a income-based annual ceiling of $200-$925; A control group included privately insured individuals	Total number of prescriptions dispensed per month	Quebec drug policy change didn’t reduce the total monthly consumption for neuroleptics and anticonvulsants, but reduced total monthly consumption for inhaled corticosteroids by 37%.
Huskamp HA et al., 2003	151,222 enrollees covered by two employers and were users of one of the following three classes of drugs: ACE inhibitors, PPIs and statins (Eligibility file and pharmacy claims data 1999–2001)	Before-after with control group	Employer A changed drug co-pay from $7/$15 to $8/$15/$30; employer B changed from $6/$12 to $6/$12/$24. Enrollees from other employers with stable 2-tier benefits were chosen as control groups	Initiation of drug therapy Adherence/compliance/MPR Rx switching Discontinuation rate Rx spending OOP and plan Rx spending	Dramatic increases in drug co-payments were associated with higher rate of discontinuation with drug therapy (21% versus 11 %) and higher Rx switching to lower cost medications (49% versus 17%), in all three drug classes. A more moderate increase in drug co-payments were associated with higher Rx switching but not higher discontinuation rates. There were no consistent effects of co-payment increase on total drug spending in three drug classes
Liu SZ et al., 2003	More than 1.6 million prescriptions for a sample of elderly patients randomly drawn from 21 hospitals in Taipei (Administrative data 1998 – 2000)	Before-after no control group	Since Aug 1999, prescription drug policy in Taiwan changed from full coverage to 20% coinsurance with a maximum of $15.625 per prescription, for prescriptions costing more than $3.125. Selected groups were exempted	Rx spending	Imposing cost-sharing was associated with a 12.86% increase in total prescription drug costs in the cost-sharing group, mainly due to an increase in average drug costs per prescription (explaining 69.20% of the variance)
Nair KV et al., 2003	8,312 patients with chronic conditions in a managed care plan (Membership data and pharmacy Claims data 2000 – 2001)	Before-after with control group	Intervention group had drug benefit changing from 2-tier to 3-tier; two control groups had stable 2 or 3 tier drug benefits	Rx switching Formulary compliance rate Discontinuation rate	Moving from a two-tier to a three-tier drug benefit was associated with an increased use of generic drugs (6 to 8 percentage points) and formulary compliance.
Rector TS et al., 2003	Pharmacy claims for three therapeutic classes (ACE inhibitors, PPIs and statins) in four independent physician practice association model health plans (1998–1999)	Before-after with control group	Four health plans changed drug benefits from two-tiered plans to three-tiered plans in different quarters during 1998–1999	Use of preferred brands	Moving from a two-tier to a three-tier drug benefit led to increases in the percentage use of preferred brands for ACEI, PPI and statins by 13.3, 8.9, and 6.0 percentage points, respectively, over a 21-month period.
Ong M et al., 2003	Monthly drug-use data for three therapeutic classes (antidepressants, anxiolytics, and sedatives) from July 1990 through Dec 1999 in Sweden	Time series	Drug co-payment increases in 1995 and 1997	Defined daily doses (DDD) per 1,000 inhabitants	Permanent increases in male antidepressants and sedatives occurred before the 1995 reform; only female antidepressant use was permanently reduced by the 1997 reform.
Artz MB et al., 2002	6,237 elderly covered by Medicare (Medicare Current Beneficiary Survey 1995)	Cross-sectional	Cross-sectional variation in drug coverage generosity	Number of filled prescriptions Rx spending	Prescription drug spending increased with drug plan generosity across a range of insurance types.
Joyce G et al., 2002	420,786 primary beneficiaries aged 18–64 with employer-provided drug benefits (Pharmacy and medical claims data 1997–1999)	Repeated cross-sectional	Cross-sectional variations of drug benefits (number of tiers, co-payments and coinsurance rates)	Rx spending OOP and plan Rx spending	Doubling co-payments decreased annual drug spending by 22% to 33% and increased the fraction beneficiaries paid out-of-pocket from 17.6% to 25.6% in a two-tier plan.
Pilote L et al., 2002	22,066 Quebec elderly patients who experienced acute myocardial infarction between 1994–1998 (Quebec Administrative claims data 1994–1998)	Before-after no control group	Drug policy changed for Quebec elderly in 1996–1997: from zero or $2 drug co-pay to %25 coinsurance plus a income-based annual out-of-pocket maximum of $200-$925	Initiation of drug therapy Medication persistence Rx switching Hospital admissions, ED visits and physician visits Mortality	Quebec drug policy change didn’t reduce use for essential cardiac medications among Quebec elderly who experienced acute myocardial infarction, nor medical utilizations. The findings did not vary by sex or socioeconomic status.
Thomas CP et al., 2002	29,435 elderly with employer-based drug benefit plans for retirees (Pharmacy claims data 2001)	Cross-sectional	Variation in drug formulary tiers, co-payment and coinsurance rates across 96 health plans	Number of filled prescriptions Rx switching Prescription size(mail/retail) Rx spending OOP Rx spending	Increased patient cost-sharing and formulary restrictions were associated with lower drug spending, higher out-of-pocket costs, and a shift to lower cost medications (generics and mail-order).
Blais L et al., 2001	259,616 Quebec elderly residents who had any prescription for the medicines under study during the whole study period: Aug 1992 to Aug 1997 (Quebec Administrative claims data 1992–1997)	Time series	Drug policy changed for Quebec elderly in 1996–1997: from zero or $2 drug co-pay to %25 coinsurance with maximum OOP payment ceiling, plus a income-based annual out-of-pocket maximum of $200-$925	Total number of prescriptions dispensed per month	Quebec drug policy change didn’t reduce total number of prescriptions dispensed per month for nitrates, antihypertensive agents, benzodiazepines, and anticoagulants.
Kozyrskyj AL et al., 2001 (a)	10,703 school-aged children in Manitoba who had asthma (Administrative data Apr 1995 – Apr 1998)	Before-after with control group	Before Apr 1996, Manitoba’s drug benefit program required a fixed deductible payment of $237 per family plus 40% co-payment on prescription costs above $237. Since April 1996 this policy was replaced by income-based deductibles with low-income family pay up to 2% of their income as deductible and high-income family pay up to 3%.	Initiation of drug therapy Number of prescription filled	Implementation of income-based deductible in Monitoba’s drug benefit policy was associated with a decrease in the use of inhaled corticosteroids by high-income children with severe asthma and did not improve use of these drugs by low-income children
Kozyrskyj AL et al., 2001 (b)	12,481 school-aged children in Manitoba who had asthma (Administrative data July 1995 – March 1998)	Repeated cross-section	Same as Kozyrskyj AL et al., 2001 (a)	Initiation of drug therapy	In comparison with higher-income children with asthma, odds ratio of receiving inhaled corticosteroid prescriptions was 0.82 – 0.88 for low-income children with asthma, controlling for asthma severity, type of drug insurance, or health care utilization patterns.
Hillman AL et al., 1999	134,937 non-elderly enrollees of nine managed care plans (Pharmacy claims data 1990–1992)	Repeated cross-section	Variation of drug co-payments both across and within health plans	Initiation of drug therapy Days of supply Rx spending	Higher co-payments for prescription drugs were associated with lower drug spending in independent practice associations (IPAs) but not in network models where physicians bear financial risk for prescription drug costs.
Motheral BR et al., 1999	3,184 individuals continuously enrolled in commercial plans from 1996 to 1997 (Pharmacy claims data 1996–1997)	Before-after with control group	Enrollees in two different employer plans experienced brand copay increase from $10 to $15, while those in the control group had brand copay of $10 during the study period	Initiation of drug therapy Number of filled prescriptions Rx switching Discontinuation rate Rx spending OOP and plan Rx spending	Increasing the co-payment from $10 to $15 was associated with lower use of brand drugs, lower plan drug spending and lower total ingredient costs. But There was no statistically significant difference in overall utilization or discontinuation rates for chronic medications.
Stuart B et al., 1999	1,302 elderly and disabled Medicaid recipients (Medicare Current Beneficiary Survey 1992)	Cross-sectional	Variation of drug co-payments across state Medicaid programs	Initiation of drug therapy Number of prescriptions filled OOP Rx spending	Imposing $0.50 - $3.0 drug co-payments in state Medicaid programs reduced drug use among elderly and disabled Medicaid recipients by 15.5% in 1992. Primary effect of co-payments is to reduce the likelihood of any prescription filling (by 7.7 percentage points). Those reporting poor health status were most adversely affected by co-payments.
Grootendorst PV et al., 1997	5,743 Ontario residents aged 55–75 (Survey data)	Cross-sectional	Discontinuity in drug benefit availability: the provision of first-dollar prescription drug insurance coverage for Ontario residents at age 65	Initiation of drug therapy Number of prescriptions filled	The provision of first-dollar prescription drug insurance coverage at age 65 increased drug use, primarily among individuals with lower levels of health status. Most of the increased use was due to the increased level of use among drug users rather than an increase in the probability of use.
Hong SH et al., 1996	3,144 children enrolled in five drug benefit plans during Dec 1992 to Dec 1993 (Pharmacy claims and enrollment database 1992–1993)	Cross-sectional	Variations in drug co-payment and cost-sharing differentials between generic and brand name drugs across five drug benefit plans	Rx initiation Number of filled prescriptions Rx spending OOP Rx spending	Higher levels of cost-sharing per prescription were associated with higher drug utilization. Larger cost-sharing differentials between generic and brand name drugs were associated with higher rates of generic drug use but were not always associated with lower expenditure rates
McManus P et al., 1996	Summary statistics on total number of prescriptions (Administrative data 1987–1994)	Time series	In Nov 1990 in Australia’s Pharmaceutical Benefits Scheme (PBS), patient contribution increased from $A11 to $A15 for the general population. In Jan 1992, a $A2.50 co-payment was required for returned service men and women.	Total monthly number of prescriptions	Increasing drug co-payment was associated with decreased level of drug consumption, but not associated with a changing trend, for both the general population and the returned service men and women. The effect was larger for “discretionary drugs”, relative to “essential drugs”.
Coulson NE et al., 1995	4,508 elderly Medicare beneficiaries in Pennsylvania (Survey data linked with administrative claims data 1989)	Cross-sectional	Variation in drug coverage generosity by different insurance types among the elderly.	Number of prescriptions filled	low-income elderly (<$12,000 single or <$15,000 married) in Pennsylvania were covered by the program of Pharmaceutical Assistance Contract for the Elderly (PACE) and only paid $4 per 30 day dosage. Enrollees of the PACE program had 0.29 more prescriptions per two-week period than did elderly who had no prescription drug coverage.
Hughes D et al., 1995	Monthly statistics in England in 1969–1992 (Published government statistics)	Time series	Over-time variation of drug co-payments in UK National Health Service	Number of non-exempt dispensed prescriptions per year per capita	A 10% increase in prescription charge was associated with a 3.2% decrease in per capita utilization of drugs within the non-exempt category
Smith DG et al., 1993	Aggregated data on use and costs of prescription drugs for 212 employer-groups covered by one managed care company in 1989	Cross-sectional	Variation of drug co-payments ($1 to $8) across employer-groups	Number of filled prescriptions Rx spending OOP and plan Rx spending	Increasing co-payments from $3 to $5 was associated with a 5% decrease in the number of filled prescriptions and a 10% decrease in employer drug spending.
Ryan M et al., 1991	Monthly statistics in England in 1979–1985 (Published government statistics)	Time series	Over-time variation of drug co-payments in UK National Health Service	Number of non-exempt dispensed prescriptions per month per capita Rx spending	10% increase in prescription drug charge was associated with 1% reduction in per capita drug utilization during the period of 1979 – 1985. Approximately two thirds of the government expenditure savings were due to reduction in utilization as opposed to increased charges on per item of drugs.
Harris BL et al., 1990	43,146 beneficiaries continuously enrolled in an HMO for a four-year period (Administrative pharmacy data 1982–1986)	Before-after with control group	The intervention group experienced co-payment rates of $1.50, $1.30, $3,00 plus other benefit changes during a three-year period while the control group of the same plan had no drug co-payment during the whole period	Number of filled prescriptions Rx spending	Graduated increases in drug co-payments (from $0 to $1.50 to $3) plus other formulary restrictions were associated with 10% to 12% reductions in the number of prescriptions and 6.7% reduction in per capita drug costs
Lavers RJ 1989	Monthly statistics in England and Wales in 1971 – 1982 (Published government statistics)	Time series	Over-time variation of drug co-payments in UK National Health Service	Number of non-exempt dispensed prescriptions per month	10% increase in prescription drug charge was associated with a 2.0% to 1.5% fall in the monthly volume of non-exempt items during the period of 1971–1982,
O’Brien B, 1989	Monthly statistics in England in 1969–1986 (Published government statistics)	Time series	Over-time variation of drug co-payments in UK National Health Service	Number of non-exempt dispensed prescriptions per month	10% increase in prescription drug charge was associated with a 3.3% fall in the volume of non-exempt items during the period of 1969–1986, the reduction was 2.3% in the sub-period 1969–1977 and 6.4% in the later period 1978–1986. Cross-price elasticity on exempted items was
Foxman B, 1987	5,765 non-elderly enrollees who participated the entire second year of RAND HIE on the fee-for-service plans in six sites	Randomized trial	Participants were randomly assigned into health plans with %0, %25, %50, %95 coinsurance rates or an individual deductible plan	Number of filled prescriptions	People with free medical care used 85% more antibiotics than those required to pay some portion of their medical bills.
Birch S 1986	Annual statistics in NHS in 1979 – 1983 (Published government statistics)	Time series	NHS patient charges on pharmaceuticals increased from 1979 to 1983. Part of the population were required to pay the charges while others were exempted from the charges.	Number of items dispensed per capita per year	During the period of 1979–1982, the per capita consumption of prescriptions in non-exempt group decreased by 7.5% while the per-capita consumption in exempted group increased by 1%.
Leibowitz A et al., 1985	3,860 non-elderly enrollees who participated the entire first year of RAND HIE on the fee-for-service plans in three sites	Randomized trial	Participants were randomly assigned into health plans with %0, %25, %50, %95 coinsurance rates or an individual deductible plan	Number of filled prescriptions Rx switching Samples from physicians Rx spending	Consumers facing a 95% coinsurance rate for prescription drugs (up to a maximum dollar expenditure) spent 57% as much as those in a free-care plan.
Reeder CE et al., 1985	62,176 Medicaid recipients in South Carolina (claims data 1976–1979)	Time series	Change in Medicaid outpatient drug co-payments since Jan 1977: from $0.0 to $0.50 per prescription	Rx spending	Imposing a $0.50 co-payment for outpatient prescriptions covered by South Carolina Medicaid programs had differential effects on the utilizations of drugs in ten various therapeutic categories. Drug utilizations dropped immediately after the co-payment increase in eight out of ten classes (except analgesics and sedatives/hypnotics). In the long-term the utilization trends in four therapeutic classes were significantly changed after the co-payment increase.
Studies that also examine the impact on medical utilization and spending
Cole JA et al., 2006	12,776 CHF patients taking ACE inhibitors, Beta blockers or both in 2002 (Claims data 2002, 2003)	Cross-sectional	Variation in drug co-payments across health plans	Medication possession ratio (MPR) Total medical costs CHF-related hospitalizations	A $10 increase in drug co-payment is associated with 2.6% and 1.8% decreases in MPRs for patients taking ACE inhibitors and Beta blockers, respectively. Such decreases were associated with predicted increases of CHF-related hospitalizations by 6.1% and 8.7%. Predicted total medical costs were not affected.
Gibson TB et al., 2006	117,366 statin users continuously enrolled in a health plan during 2000–2003 (Pharmacy and medical claims data 2000–2003)	Repeated cross-sectional	Variation in statin co-payments across health plans	MPR Hospital admissions ED visits Physician visits	A $10 increase in co-payment resulted in a 1.8 and 3.0 percentage point reduction in adherence, among new and continuing statin users, respectively. For continuing users, higher statin adherence was associated with lower negative events (hospital admissions and ED visits) but not with total costs.
Mahoney JJ et al., 2005	Diabetes-related claims and drug use and cost statistics in one company (2001–2003)	Before-after no control group	One company reduced coinsurance rates on diabetes drugs to 10% (from 25% to 50%) in Jan 2002.	Adherence Rx spending Rx + Medical spending ED visits	From 2001 to 2003, adherence and use of fixed-combination therapy had increased among diabetes patients. Average total pharmacy costs had decreased by 7% and overall medical costs decreased by 6%. ED visits had decreased by 26%.
Winkelmann R, 2004	37,319 individuals in Germany (Survey data 1995–1999)	Before-after with control group	Co-payment for prescriptions increased by 6 DM in 1997. Certain groups were exempted from such an increase and served as the “control” group	Physician visits	In Germany, An additional 6 DM prescription fee reduced the number of doctor visits by 10% on average.
Fairman KA et al., 2003	7,709 enrollees in a PPO (Pharmacy and medical claims data 1997–2000)	Before-after with control group	Enrollees in the intervention group experienced a formulary change from 2-tier to 3-tier; Enrollees in the control group had stable 2-tier formulary	Number of filled prescriptions Rx Continuation rate Rx spending OOP and plan Rx spending Hospitalizations, ED visits and ambulatory visits	Moving from a two-tier to a three-tier drug benefit was associated with reduced growth in plan cost and lowered utilization of non-formulary medications, but not associated with lower growths of total prescription claims or total drug spending. The associations between adding tiers and drug continuation rates were mixed for four classes of chronic medications. Such drug benefit change was not associated with number of hospitalizations, ED visits or office visits
Balkrishnan R et al., 2001	2,411 Medicare HMO enrollees in 1998 and 1999 (Data source unknown)	Before-after no control group	In 1998, co-payments were $7/$15, for generics and brand names, separately, with quarter OOP maximum of $200. In 1999, there was unlimited coverage for generics and limited coverage for brand drugs.	Plan Rx spending Plan Rx + medical spending Physician visits	Changing to a drug policy with unlimited coverage for generics and limited coverage for brand drugs was associated with 27% decrease in plan drug costs, 4% decrease in physician visits and 5% decrease in plan total costs
Motheral BR et al., 2001	20,160 individuals continuously enrolled in a PPO from Jan 1997 to Dec 1999. (Pharmacy and medical claims data 1997–1999)	Before-after with control group	Enrollees of the intervention group had drug benefit changed from 2-tier to 3-tier. Those in the control group has stable 2-tier benefit	Initiation of drug therapy Number of filled prescriptions Rx Discontinuation rate Rx spending OOP and plan Rx spending Hospitalizations, ED visits and ambulatory visits	Moving from a two-tier benefit with co-payments of $7/$12 to a three-tier benefit with co-payments of $8/$15/$25 was associated with slower growth in prescription drug utilization and drug spending (15% vs. 22%). Adding tiers were not consistently associated with medication discontinuation rates of four chronic therapy classes, and not associated with hospitalizations, ED visits or office visits
Tamblyn R et al., 2001	149,283 Quebec residents 65 years and older or receiving welfare (Administrative data 1993–1997)	Time series	Drug policy changed for Quebec elderly in 1996–1997: from zero or $2 drug co-pay to %25 coinsurance plus a income-based annual out-of-pocket maximum of $200-$925	Mean daily drug use Serious adverse events (acute care hospitalizations, long-term care admission, or death)	Quebec drug policy change was associated with a 9% and 14% reduction in use of essential drugs, for elderly and welfare recipients respectively. Such reductions were associated with increased number of serious adverse events and ED visits. Use of less essential drugs decreased by 15% and 22%.
Berndt ER et al., 1997	3,470 privately insured individuals from 26 plans treated for depression in 1993 (Medical and pharmacy claims 1993)	Cross-sectional	Variations of drug copayment across 26 health benefit plans	Initiation of drug therapy Hospitalizations	Among depressed patients receiving outpatient treatment, higher prescription drug copayment was associated higher share of SSRI utilizations in all anti-depressant medications; higher drug copayment was not associated with higher probability of hospitalizations
Johnson RE et al., 1997(a)	Elderly HMO members during a four-year period (Administrative data 1987–1991)	Before-after with control group	Two Medicare risk groups in an HMO setting had their co-payments and coinsurance rates increased in different years during a three-year period	Initiation of drug therapy Days of supply Rx spending Health status index	Graduated increases in co-payments from $1 to $5 and coinsurance (from 50% to 70%, with a $25 max) did not reduce prescription drug utilization and costs in a consistent manner among each of twenty-two therapeutic drug classes. Health status may have been adversely affected as measured by Combined Chronic Disease Score and Diagnostic Cost Groups.
Johnson RE et al., 1997(b)	Elderly HMO members during a four-year period (Administrative data 1987–1991)	Before-after with control group	Two Medicare risk groups in an HMO setting had their co-payments and coinsurance rates increased in different years during a three-year period	Number of filled prescriptions Rx spending OOP Rx spending Hospitalizations, ED visits and ambulatory visits Rx + Medical spending	Graduated increases in co-payments from $1 to $5 and coinsurance (from 50% to 70%, with a $25 max) resulted in lower prescription drug uses and expenses, and did not affect medical care utilization and expenses in a consistent manner.
Lingle EW et al., 1987	9,966 elderly Medicare beneficiaries and not eligible for Medicaid benefits (1975 and 1979) (Medicare claims data 1975,1979)	Before-after with control group	The intervention group includes Medicare beneficiaries covered by New Jersey’s Pharmaceutical Assistance for the Aged (PAA); the control group includes beneficiaries in eastern Pensylvania	Medical utilization Plan medical spending	Re-imbursement for in-patient care for New Jersey’s PAA recipients was on average 238.50 lower than that in eastern Pensylvania. There was no significant increase in total medical costs reimbursed by Medicare among New Jersey’s PAA recipitents.