Study Characteristics
Of 1,390 articles identified by the literature searches and additional checks, 1,321 were excluded based on their titles and abstracts (Fig. 1. Study Flow Chart). Sixty-nine studies were screened in full text with 43 eliminated at this stage, leaving 26 included studies (study details in Table 1).(2, 3, 35–58) Since several of these studies used the same source survey.(3, 38, 39, 43, 45, 46, 54, 55) the total sample size of unique participants across all 26 studies is uncertain. Assuming that each study’s participant is a unique individual, the total sample size is 497,534. All but one of the studies were observational, varying from surveys to large healthcare database time series, to qualitative designs. The summary risk of bias was rated as low for eight studies, moderate for nine, and high for nine studies (details in Fig. 2).
Prevalence of Medication CRNA in Canada
Sixteen studies, excluding a medication-specific survey(56), addressed the prevalence of CRNA (n = 105,109 potential participants) (Table 1).(2, 3, 35–46, 54, 55) Using somewhat differing definitions for CRNA and different sampling frames, these studies suggested prevalence between 3.6% and 15.0%.(2, 3, 35–46, 54, 55) Ten of these studies providing more generalizable and population-level analyses (ie, not highly selected sub-groups such as the homeless or those with several chronic conditions) based on large national or international surveys suggested rates of 5.1–10.2%.(3, 36, 38–40, 43–46, 55) The Joint Canada-US Survey of Health telephone survey in 2002 included 3505 Canadian adults, 5.1% of whom reported CRNA.(36) In the International Health Policy telephone surveys, 8.0% of the sampled Canadian adults reported CRNA in 2007, and 10.2% in 2016.(38, 39, 44) The CRNA section of the Canadian Community Health Surveys (CCHS) found that 9.6% of adults who received a prescription reported CRNA in 2007 compared to 5.5% overall in 2016.(40, 46) The 2007 analysis suggested geographic variability, with higher rates of CRN in British Columbia than other regions.(46) Two studies examined different subgroups of the 2016 CCHS.(54, 55) Two additional studies estimated CRNA in specific sub-groups groups of Canadian patients, and reported rates of 10.2% in Canadians with comorbidities and 8.3% in participants with food insecurity.(37, 41)
Predictors of CRNA
Nineteen studies (n = 440,064 potential participants) provided information on the predictors of CRNA (details in Table 1).(2, 3, 35, 37–41, 43, 46–52, 54, 55, 57, 58) Thirteen studies (n = 70,636) analyzed multiple potential factors based on direct reporting from study participants. (2, 3, 35, 37–41, 43, 46, 51, 54, 55) Five additional studies (n = 369,416) involving large administrative databases used time series methods with or without pre-post analyses of policies which changed the amount of patient cost-sharing in provinces, to suggest that increased out-of-pocket expenditures for drugs is a predictor of non-adherence assumed to be CRNA.(47–50, 52)
Several factors emerged as independent predictors in the studies using multivariable analyses. In order of high to low frequency of mention, these were: high out-of-pocket expenses on medication, lower household income or financial flexibility, lack of drug insurance, younger age, poor self-reported health, province of residence, and miscellaneous (Table 2). (2, 3, 35–41, 43, 46–55, 57) The analysis of the CRNA module within the 2007 CCHS was the largest and most detailed, showing a prevalence of 11.4% for the 35 to 44 years age group compared to 4.8% for subjects older than 65 years.(40) In the multivariable analysis, odds ratios were 4.5 for lack of drug insurance, 3.3 for low household income. 20.1% of participants reporting poor health also reported CRNA compared to 10.4% of subjects reporting good health (OR 2.64, 95% CI 1.77–3.94).(40) Finally, factors which may reflect differences amongst jurisdictions including their policies, were also independent predictors. Amongst those younger than 65 years, respondents in the 2014 International Health Policy Survey (IHPS) who were from Quebec were less likely to report CRNA than those residing in Ontario (OR 0.5, 95% CI 0.3–0.8).(43) At the time, while drug insurance was compulsory in Quebec, Ontario reimbursed non-seniors only for those who were socially disadvantaged or had very high medication costs.(43) In the 2007 CCHS, residence in British Columbia where a significant portion of public drug coverage has income-based deductibles was associated with more CRNA compared with Ontario (OR 2.56, 95% CI 1.49–4.42).(40)The IHPS segment of Canadians self-identifying as First Nations, Inuit or Metis, were at higher risk of CRNA (RR 2.1, 95% CI 1.4–3.2).(39) Although the publicly funded Non-insured Health Benefits Program includes drug benefits without co-payment or deductible, these apply only to those considered ‘status Indians’ or Inuk and require providers to register with the program to avoid initial self-pay.(59)
Three studies in BC using a similar cohort with similar methodology examined the influence of increased out-of-pocket expense by analyzing the effect of changes in drug insurance coverage on adherence measured by prescription dispensing intervals.(48–50) The utilization of maintenance respiratory inhalers declined by approximately 5.8 to 12.3% (p < 0.001), the rate of full adherence to statins decreased by 5.4% (95% CI, 6.4–4.4%) but adherence to beta-blockers was only modestly reduced (approximately 1%) compared to full coverage.(48–50) Non-adherence was associated with higher out-of-pocket expenditures, with beta-blockers thought to be less affected because of their low cost compared to the other drug groups at the time of the study.(50) For statins, adherence was better in high risk patients with prior vascular events compared to the entire group.(49) An analysis of a policy change to lower seniors’ out of pocket prescription drug costs in Saskatchewan in 2007, found a small increase in optimal medication adherence after the policy change.(47)
CRNA Association with Clinical Outcomes
Only three studies measured clinical outcomes potentially related to CRNA (Table 1; n = 93,653).(52, 53, 58) The highest quality study was a recent randomized controlled trial involving patients in primary care in Ontario who reported that they did not fill a prescription or changed regimens to make their supply last longer because of the cost. The study found that the intervention group provided free, mailed prescriptions deemed essential, reported better adherence, improved perceived care, and less concern about making ends meet at 12 months follow-up. Several surrogate outcomes were followed, with improvement in blood pressure in the intervention group for those requiring anti-hypertensives but no significant improvement in A1C or cholesterol. However, there was no difference in hospitalizations, serious adverse events or death.
The introduction of a drug policy in Quebec in the nineties increased out-of-pocket costs for all residents. In one retrospective study, this led to a decrease in the overall number of drugs used per day by the elderly and by welfare recipients, including ‘essential’ medications such as aspirin and furosemide (decrease of 9.1% − 14.4%) as well as symptomatic but potentially harmful drugs such as benzodiazepines (decrease of 15.1% − 22.4%). The decline in use of essential drugs was associated with a small increase in serious adverse events including death, hospital or nursing home admission, or emergency department visits.(52) In a second retrospective study, there was no change in adherence to post-myocardial infarction medication adherence and no change in clinical outcomes after the policy compared to pre-policy.(53)