Table-3.

Studies examining the impact of reference pricing (RP) on prescription drug utilization and spending, medical utilization and spending (16 studies)

Author	Study sample	Study design	Drug benefit variation	Outcomes	Key findings
Studies that examine the impact on prescription drug utilization only
Mabasa VH et al., 2006	PPI prescriptions for Canadians with private employer-sponsored drug plans (Claims data June 2002-May 2005)	Before-after with control group	One employer group adopted reference pricing for PPIs since June 2003, while other employer groups didn’t have reference pricing for PPIs through the whole study period	Number of days supplied Rx spending	Introduction of reference-based pricing for PPIs in one employer in Canada reduced plan spending on PPIs by approximately 26%. Less than one third of the reduction was attributed to average price of PPIs and more than two thirds to a decline of utilization of PPIs.
Grootendorst PV et al., 2005	British Columbia Pharmacare for the elderly (Aggregated data 1993–2001)	Time series	Pharmacare introduced two types of RP for NSAIDs: Type I in Apr 1994 and Type II in Nov 1995. Under Type I RP, generic and brand versions of the same NSAIDs were exchangeable, under Type II RP, different NSAIDs were considered interchangeable.	Rx plan spending	Imposing reference pricing among all NSAIDS (Type 2 RP) achieved more savings compared to a reference pricing among each NSAID(Type 1 RP). After Type 2 RP, annual plan expenditures for NSAID were cut by $4 million (50%). Most savings accrued from the substitution of low-cost NSAIDs for most costly alternatives. About 20 percent of savings represented expenditures by seniors who paid cost-sharing NSAIDs.
Schneeweiss S et al., 2004	British Columbia Pharmacare for the elderly (Aggregated data 1995–1998)	Before-after no control group	Introduction of reference pricing to ACE inhibitors in elderly BC residents in 1997	Rx plan spending	RP to ACE inhibitors in elderly BC residents was associated with savings of CAN $6 million among continuing users and $0.2 million among new users, during the first year of the implementation. Approximately five sixths were achieved by utilization changes and one sixth by cost shifting to patients. There were no savings through drug price changes
Marshall JK et al., 2002	BC Pharmacare beneficiaries (Aggregated data 1993–1999)	Time series	Introduction of reference pricing to H2RAs and special authority for PPIs in elderly BC residents in 1995	Number of defined daily doses per 10,000 beneficiaries OOP and plan drug spending per 10,000 beneficiaries	RP for H2RAs and special authority for PPIs reduced plan expenditures by $1.8 to $3.2 million per year for H2RAs and $5.5 million per year for PPIs. Beneficiary contributions for H2RAs increased from negligible amount to approximately 16% of total drug expenditures
Schneeweiss S et al., 2002	119,074 BC Pharmacare beneficiaries who used ACE inhibitors from 1995–1998 (Administrative data 1995–1998)	Longitudinal	Introduction of reference pricing to ACE inhibitors in elderly BC residents in 1997	Number of prescriptions Plan Rx spending Rx switching Discontinuation rates	RP for ACE inhibitors was associated with 11% reduction in use of all ACE inhibitors. But the use of overall antihypertensives was unchanged. The policy saved $6.7 million in pharmaceutical expenditures for existing users during its first 12 months. Relative to high-income patients, patients with low-income status were more likely to stop all antihypertensive therapy (OR 1.65)
Aronsson T et al., 2001	Quarterly time-series data on prices and quantities for twelve brand-name drugs and their generic substitutes from 1972–1996	Time series	Introduction of reference pricing in 1993 which specifies that any costs exceeding the price of the least expensive generic substitute by more than 10% must be borne by patients	Market share of brand-name drugs Relative price of brand-name versus generics	Introduction of reference pricing was negatively associated with market shares for three brand-name drugs while positively associated with market shares for other two. Reference pricing was also associated with decreased relative price of brand-name versus generics.
Grootendorst PV et al., 2001	BC Pharmacare for the elderly (Aggregated data 1994 – 1999)	Before-after no control group	Introduction of reference pricing to nitrates in elderly BC residents in 1995	Monthly total number of prescriptions Plan and OOP Rx spending	During three and a half years after introduction of RP for nitrates, BC Pharmacare expenditures on nitrates for the elderly declined by $14.9 million. Most of these savings were due to the lower prices that Pharmacare paid for restricted nitrates. Prescribing of reference-standard nitrates increased immediately after the policy was introduced but later dropped after nitroglycerin patch was exempted from additional charges. $1.2 million of the savings represented expenditures by senior citizens who bought restricted nitrates. There were no compensatory increases in expenditures for other anti-angina drugs
McManus P et al., 2001	Prescriptions in Australia which were under government subsidy (Claims data 1990, 1994 and 1999)	Before-after no control group	Introduction of minimum pricing policy in Australia in 1990 and generic substitution policy in 1994	Rx switching	After implementation of minimum pricing, share of generic drugs increased from zero in 1990 to 17% in 1994. Generic substitution policy further increased the share to 45% in 1999.
Narine L et al., 2001	BC Pharmacare for the elderly (Aggregated data 1994–1996)	Before-after no control group	In 1995, the BC Pharmacare introduced a reference-based pricing (RBP) system for H2 antagonists, nitrates, and NSAIDs	Plan Rx spending Total number of prescriptions Rx switching	Introduction of RBP was associated with a 44% decrease in Pharmacare drug costs. Total number of prescriptions for H2 antagonists and nitrates decreased by 5.2% and 2.5%, respectively. A significant number of patients were switching from one drug to the other after introduction of RBP.
Narine L et al., 1999	BC Pharmacare (Aggregated data 1994 – 1996)	Before-after no control group	Introduction of reference pricing to H2RAs in elderly BC residents in 1995	Annual total number of prescriptions Plan Rx spending	In the year following the introduction of RP for H2RAs, the total number of prescriptions decreased by 5.2%, the market share of reference drug increased by 410%. Pharmacare expenditures for Histamine-2 receptor antagonists decreased by 38%. There was no substantial changes in drug prices
Jonsson B., 1994	Swedish reimbursement system for drugs (Aggregated data 1992–1993)	Before-after no control group	Introduction of a reference price system on Jan 1993	Plan Rx spending OOP Rx spending	During the first three months of the introduction of a reference system in Sweden, relative to the same period in the previous year, there was a slight decrease (1.6%) in total expenditure for the reimbursement scheme (NSIB) but a 14% increase for patient co-payments.
Studies that also examine the impact on medical utilization and spending
Schneeweiss S et al., 2006	5 million BC elderly residents (Administrative data Jan 2002 to June 2004)	Longitudinal	Beginning at 2003, BC Pharmacare program only covered one PPI: rabeprazole, and imposed access restrictions on three leading PPIs	Defined daily doses per month Rx discontinuation rates Rx spending Gastrointestinal hemorrhage rates	Within 6 months after policy change, 45% of all PPI users switched to the covered PPIs, and the provincial health plan saved at least Can $2.9 millions. There were no increased use of H2 blockers, discontinuation of gastroprotective drugs or hospitalizations for hemorrhage.
Schneeweiss S et al., 2004	5,463 patients covered by British Columbia Pharmacare with at least one prescriptions for a nebulised respiratory drug in the preceding 12 months (Administrative data Sep 1997 - Aug 1999)	Randomized controlled trial Observational time series	Since March 1999, Pharmacare restricted reimbursement for nebulised respiratory medications to patients with doctor’s exemption. Patients in the intervention group in a randomized control trial were not subject to this restriction for six months.	Rx utilization Rx spending Contacts with doctors and services Emergent admissions to hospitals	both in the randomized control trial and the observational analysis found that restricting reimbursement for nebulised respiratory drugs was not associated with increase of unintended health outcomes,
Schneeweiss S et al., 2003	61,763 elderly British Columbia residents who were dihydropyridine CCBs users and covered by Pharmacare (Administrative data 1995–1997)	Longitudinal	Introduction of reference pricing to dihydropyridine CCBs in elderly BC residents in 1997	Median monthly doses Rx switching Hospital admissions ED visits Admissions to long-term care facilities	RP to dihydropyridine CCBs was associated with increased use of fully-covered dihydropyridine CCBs and reduced total medical costs by Canadian $1.6 million in the first 12 months of implementation. Overall antihypertensive use did not decline, and there were no increases in hospitalizations, ED visits or long-term care admissions.
Hazlet TK et al., 2002	20,000 British Columbia Pharmacare beneficiaries exposed to Histamine-2 receptor antagonists (H2RAs) and other antisecretory drugs from 1993 through 1996 (Administrative data 1993–1996)	Longitudinal	Introduction of reference pricing to H2RAs in elderly BC residents in 1995	Number of prescriptions filled Hospital visits ED visits Hospital admissions Length of hospital stay	RP to H2RAs in elderly BC residents was not associated with worsening health outcomes among antisecretory drug users.
Schneeweiss S et al., 2002	37,362 BC Pharmacare beneficiaries who used selective ACE inhibitors before the RP policy for ACE inhibitors (Administrative data 1995–1998)	Longitudinal	Introduction of reference pricing to ACE inhibitors in elderly BC residents in 1997	Hospital admissions ED visits Admissions to long0term care facilities RX plan spending	RP for ACE inhibitors was not associated with cessation of treatment or changes in the rates of visits to physicians, hospitalizations, admissions to long-term care facilities, or mortality. Net savings were estimated to be $6 million during the first 12 months of reference pricing