Table 2.
Summary of study results and quality assessment (n = 21)
| Author, year | Results | MMAT Score |
|---|---|---|
|
| ||
| Multiple comorbidities | ||
| Birand, 2019 [33] | • Pts. who had a negative balance between their beliefs about the necessity of the medication and their concerns were less likely to adhere to the medication (OR 0.138, 95% CI 0.025–0.772) • Among all participants, 91.4% were identified as adherent post intervention (patient education on adherence and rational drug use) and 8.6% were non-adherent (P < 0.0001) • Adherent pts. showed sig. higher specific necessity belief scores compared to non-adherent pts, and non-adherent pts. showed sig. higher general overuse and harm belief scores than adherent pts. (P < 0.05) |
• 100% |
| Calip, 2017 [34] | • 37% were non-adherent to antihypertensives (out of 1,1779 users) • 75% were non-adherent to diabetes medications (out of 499 users) • 39% were non-adherent to statins (out of 1,072 users) • In adjusted models, younger age was associated with non-adherence to all three therapeutic classes • Certain cancer treatments were modestly associated with non-adherence to antihypertensives (radiation: OR 1.21, 95% CI 1.01–1.47; endocrine therapy: OR 1.27, 95% CI 1.03–1.52) and diabetes medications (chemotherapy: OR 1.69, 95% CI 1.17–2.21) • Less frequent primary care provider visits were associated with higher odds of non-adherence to antihypertensives (OR 1.70, 95% CI 1.19–2.22) • Trends showed higher Charlson comorbidity scores associated with greater adherence to diabetes medications (P < 0.001) and statins (P = 0.032) |
• 100% |
| Dashputre, 2019 [35] | • Across all 3 cancers, patients prescribed lipid-lowering agents experienced most sig. declines in adherence post-oncologic initiation (MM: – 15.6%, P < 0.0001; CML: – 13.1%, P < 0.0001; CLL/SLL: – 10.7%, P = 0.01) • D-in-D models revealed consistent and sig. differences in changes of adherence to antihypertensives (CML: 5.1% vs. 11.3%, P = 0.03; CLL/SLL: 5.2% vs. 13.9%, P = 0.007; MM: 10.4% vs. 13.1%, P = 0.09); sensitivity analyses yielded similar results • No sig. differences for those taking antidiabetic agents • Amongst those adherent to comorbid therapy in baseline, non-adherence to oral oncolytics was associated with higher odds of non-adherence to comorbid therapy in follow-up, with sig. higher odds of non-adherence to antihypertensives in follow-up across all 3 cancers (CML: OR 1.90, 95% CI 1.06–3.42; CLL/SLL: 2.17,1.23–3.82; MM: 1.53, 1.18–1.99) and higher odds of non-adherence to lipid-lowering agents for CLL/SLL (2.51,1.18–5.32) and MM (1.52, 1.04–2.22) |
• 80%; unadjusted D-in-D models |
| Drzayich Antol, 2018 [36] | • Low adherence to comorbidity medication was reported by 29.5% of pts • Pts. with a higher comorbidity level were more frequently moderately or highly adherent to their comorbidity medication regimens • Pts. w/low comorbidity medication adherence reported a median of 15 total unhealthy days compared to 10 total unhealthy days for patients w/moderate or high comorbidity medication adherence (P < 0.05) • Pts. w/low comorbidity medication adherence reported more frequent mental and physical unhealthy days than pts. w/ moderate/high comorbidity medication adherence (30.3% vs 20.2%, P < 0.001; 38.7% vs 33.6%, P = 0.049) • Pts. reporting low comorbidity medication adherence had 23.4% more unhealthy days than pts. w/ moderate/high comorbidity medication adherence (P = 0.007) • A higher comorbidity index was the only factor observed as protective against the odds of low comorbidity medication adherence |
• 100% |
| Santorelli, 2016 [37] | • During the post-baseline period, the percentage of BC pts. who were non-adherent were 26.2% for diabetes medication, 28.9% for lipid-lowering medication, and 14.2% for hypertension medication • BC pts. experienced increased odds (44%) of diabetes medication non-adherence relative to women without cancer (P = 0.02) (effect was similar in sensitivity analyses) • Odds of hypertension medication non-adherence was 24% lower for pts. with BC than those w/o cancer (P < 0.01; when PDC < 90%) • No difference between BC and comparison women in the odds of non-adherence to lipid-lowering medication • Findings of non-persistence were similar to non-adherence → probability of non-persistence with diabetes medication was higher for women w/ BC compared to women w/o cancer, while the probability of non-persistence with HTM medication was lower for women w/BC relative to comparators • Women w/BC experienced a 31% increase in the hazard for diabetes medication non-persistence relative to women w/o cancer (P = 0.02), while women w/BC experienced a 27% decrease in hazard for hypertension medication non-persistence relative to comparators (P < 0.01) • The odds of non-adherence was higher in the post-baseline period relative to the prebaseline period for both the BC and comparison women in all three cohorts |
• 100% |
| Yang, 2016 [38] | • Average adherence to non-cancer medications before cancer diagnosis was 91.4%; after ESBC treatment, average adherence decreased to 77.9% (P < 0.001) • The largest decline in adherence was observed for osteoporosis medications (83.5 to 45.5%; P < 0.001), followed by diabetes medications (79.9 to 53.1%; P < 0.001) and hyperlipidemia medications (83.2 to 57.1%; P < 0.001) • Looking at drugs for each condition, non-adherence ranged from 15.6 to 38% (P < 0.001) • Older age, insurance type, number of medications, and comorbid conditions were associated with non-adherence |
• 100% |
| Zhou, 2019 [39] | • During follow-up period, 74.1% of the allogeneic HCT recipients and 68.3% of the autologous HCT recipients experienced treatment gaps for oral diabetes meds. compared to 54.3% in chemo-only group at 12 months after transplantation • A total of 67.1% of the allo HCT recipients and 60.0% of the auto HCT recipients had treatment gaps of oral antihypertensive meds. at 12 months compared to 47.8% in chemo-only group • For pts. with dyslipidemias, 79.0% of the allo HCT recipients and 63.1% of the auto HCT recipients experienced treatment gaps or oral lipid-lowering meds. at 12 months compared to 53.2% in chemo-only group • Sig. differences in medication adherence observed in allo HCT cohort (P < 0.001) and auto HCT cohort (P = 0.017) for lipid-lowering meds, compared with chemo-only cohort • Allo HCT pts. had greater risk of discontinuation of oral diabetes meds (HR = 1.93, 95% CI 1.10–3.39), hypertension (HR = 1.75, 95% CI 1.21–2.53), and dyslipidemias (HR = 2.02, 95% CI 1.39–2.93) compared to matched chemo-only cohort • Allo HCT recipients were less likely to be adherent to antihypertensive meds. (OR = 0.58, 95% CI 0.38–0.89) and lipid-lowering meds. (OR = 0.38, 95% CI 0.22–0.65); auto HCT recipients were less likely to be adherent to lipid-lowering meds. (OR = 0.73, 95% CI 0.53–0.995) • Younger age was associated with suboptimal adherence to diabetes and hypertensive meds |
• 100% |
| Diabetes | ||
| Calip, 2015 [40] | • Compared to year – 1, mean MPR for metformin/sulfonylureas (0.86 versus 0.49, P < 0.001) and %-adherent (75.3% versus 24.6%, P < 0.001) declined during breast cancer treatment • MPR and %-adherent rose slightly during years 1–3 post diagnosis but never returned to baseline • Discontinuation rate increased from treatment to year + 1 (59.3% versus 75.6%, P < 0.001) and remained elevated during subsequent observation periods |
• 80%; unadjusted models |
| James, 2018 [41] | • No sig. difference in self-management behaviors at enrollment compared with 3-month follow-up (57% vs. 65% adherent to their oral diabetes medication) • No differences in self-management behaviors by age, race, income, cancer type, or presence of anxiety • Compared to pts. w/o avoidant thoughts, pts. w/ avoidant thoughts were less likely to adhere to diabetes medications (77% vs. 30%, P = 0.02) • Adjusted regression did not show an independent association between elevated total PTSD symptoms and adherence to medications • Pts. w/avoidant thoughts about their cancer were less likely to be adherent to their diabetes medications (OR: 0.17, 95% CI: 0.03–1.00) • No sig. associations with pts. w/ intrusive thoughts about cancer and diabetes self-mgt |
• 80%; potential for differential factors in responders and non-responders |
| Letinier, 2018 [42] | • For cancer subjects, avg. duration of oral diabetes treatment before cancer was 29.6 months • One quarter of non-cancer and half of cancer subjects definitively stopped oral diabetes medication after a first discontinuation of ≥ 90 days • Estimated cumulative non-persistence incidence probabilities were 0.39 over the year after oral diabetes treatment initiation and 0.51 over the following 3 years; a higher risk of non-persistence was observed over the first year of f/up • A cancer occurrence sig. increased the cause-specific HR of non-persistence by 93% (similar results in sensitivity analyses) • A cancer occurrence sig. increased the specific HR of non-persistence for CRC, pulmonary, and other cancer groups; association btw. breast or prostate cancer was close to the sig. threshold of 0.05 |
• 100% |
| Stuart, 2015 [43] | Overall, PDC declined after index date for OHAs (3.7%), RAAS-Is (5.3%), and statins (3.2%) for individuals with cancer compared with controls (all P < 0.001) • Overall, individuals diagnosed with cancer had larger pre-post declines than controls for OHAs (− 8.5%; P < 0.01), RAAS-I (− 10.7%; P < 0.001), and statins (− 9.3%; P < 0.01) • Declines in PDC were larger for individuals with short life expectancy relative to those with longer-term survival for RAAS-I (− 6.1%; P < 0.05) and statins (− 6.7%; P < 0.05), whereas the effect was smaller and not significant for OHAs • The PDC values for all three drug classes declined in both the LIS and non-LIS subgroups for cancer survivors relative to controls |
• 100% |
| Tan, 2016 [44] | • Average MPR among all pts. w/ cancer was 0.60 • 62.4% diabetic cancer v. 64.2% diabetic non-cancer non-adherent (no sig. difference, P = 0.24) • 37.6% diabetic, cancer pts.newly initiated on oral diabetic medication adherent to oral diabetic medications; similar adherence proportion in non-cancer control population (35.8%, P = 0.24) • Breast and prostate higher adherence trend than colon and lung cancers (no sig. difference) • More sulfonylureas and TZD (mono/combination therapy) non-adherent than metformin & DPP-4 inhibitors (P = 0.02 and P = 0.01, respectively) • Monotherapy associated w/better adherence than combination therapy (P < 0.001) • Adherence sig. associated w/ demographics and medication-related factors — not clinical status • Younger (18–54) less adherent than older (61–64) (OR = 0.70, P = 0.006) • Mail order 33% more likely adherent than retail (P = 0.02) |
• 100% |
| Zanders, 2015 [45] | • MPR increased 0.10% per month before cancer diagnosis (95% CI: 0.10, 0.10) • Sig. MPR drop at time of cancer diagnosis (− 6.3%; 95% CI: – 6.5, – 6.0) and ongoing, yet lower monthly MPR decline after cancer diagnosis (− 0.20%, 95% CI: – 0.21, – 0.20) → indicating a clear decline in medication adherence because of cancer • No sig. MPR decline at time of breast/prostate cancer diagnosis, but large MPR decline at time of other GI and pulmonary cancers (~ 0.5% each month) • Higher TNM stage associated w/greater observed medication adherence decline • Chemotherapy or radiotherapy administration no effect modification • Pts. who did not receive surgery had more pronounced drop in MPR at cancer diagnosis (− 10.8%; 95% CI: – 11.2, – 10.4) than those who did receive surgery (− 2.8%; 95% CI: – 3.1, – 2.4) • Impact of cancer on adherence was sig. for all age grps., but larger decreases in MPR observed w/increasing age • The impact of cancer diagnosis on MPR most apparent w/ sulfonylurea + metformin and insulin monotherapy or combination therapy at cancer diagnosis |
• 100% |
| Hyperlipidemia | ||
| Banegas, 2018 [46] | • Statin adherence decreased from pre- to post-cancer diagnosis (aOR: 0.91, 95% CI 0.88–0.94, P < 0001) • Statin adherence decreased from pre- to post-cancer diagnosis among breast (aOR: 0.94, 95% CI: 0.90–0.99, P = 0.011) and colorectal (aOR: 0.79, 95% CI: 0.74–0.85, P < 0.001) cancer patients • There was no difference in adherence observed among prostate cancer patients (aOR: 1.01, 95% CI: 0.97–1.05, P = 0.657) |
• 100% |
| Calip, 2013 [47] | • Mean MPR for statin use (0.78 vs. 0.68; P = 0.001) and proportion adherent (67.0 vs. 51.9%; P = 0.001) declined from baseline to cancer treatment period • Lowest MPR observed in year 2 (of treatment years) (0.63 and % adherent 35.9%) • Proportion of users that did not experience a discontinuation episode at baseline was 50.5% and greatest in the treatment period (57.7%; P < 0.001) • During treatment, non-adherent statin users had the highest mean LDL (160.4 mg/dL) and proportion not at goal LDL (91.8%) overall • Adherence did not return to baseline in subsequent years following treatment although LDL levels did • Mean HDL and proportion not at HDL goal did not differ by periods of interest or adherence levels • Adherence to statins in this population was poor, particularly in the treatment period, and lagged in returning to baseline |
• 80%; unadjusted models |
| Feng, 2021 [48] | • Each 10% increase in 1-year adherence to LLMs was associated with an 8% reduction in breast cancer mortality (fully adjusted hazard ratio (HR) = 0.92, 95% CI 0.91–0.93) • The HR for non-cancer mortality was also statistically significantly reduced (0.93, 95% CI 0.92–0.94). Findings were similar for use of any statins and lipophilic statins but were less marked for hydrophilic statins (breast cancer mortality, fully-adjusted HR = 0.96, 95% CI 0.94–0.99; non-cancer mortality, fully-adjusted HR = 0.97, 95% CI 0.94–0.99 • Similar 8% reductions between each 10% increase in 1-year adherence to LLMs, any statins, or any lipophilic statins and colorectal cancer mortality and non-cancer mortality • Reduction in colorectal cancer mortality was slightly less apparent for patients who increased 10% of 1-year adherence to hydrophilic statins (fully adjusted HR = 0.96, 95% CI 0.93–0.98) • Each 10% increase in 1-year adherence to LLMs reduced melanoma mortality and non-cancer mortality after adjustment for age (HR = 0.96, 95% CI 0.93–0.99 and HR = 0.94, 95% CI 0.92–0.96, respectively). After further adjustment for multivariables, the corresponding inverse associations were slightly attenuated for melanoma mortality (HR = 0.97, 95% CI 0.94–1.00) but slightly improved for non-cancer mortality (HR = 0.93, 95% CI 0.92–0.95). A weak reduction in melanoma mortality was observed in lipophilic statin users (fully adjusted HR = 0.99, 95% CI 0.95–1.02) • No statistically significant association in melanoma mortality among hydrophilic statin users |
• 100% |
| Hypertension | ||
| Jeong, 2015 [49] | • No significant differences in smoking, physical activity, antihypertensive medication adherence (aOR: 0.54, 95% CI: 0.19–1.54, P = 0.251), or self-reported diet control • Good medication adherence for BC survivors and non-cancer controls was 81.3% vs. 88.8%; poor medication adherence was 18.7% and 11.2% for cancer and non-cancer pts., respectively |
• 100% |
| Jo, 2015 [50] | • No significant difference in antihypertensive medication adherence among gastric cancer survivors and non-cancer controls (aOR = 1.66; 95% CI: 0.77–3.57; P = 0.195) | • 80%; approach for assessing adherence was not reported |
| Shin, 2010 [51] | • Cancer survivors less likely have appropriate medication adherence than general population (lower CMA) (54.4% vs. 57.5%; aOR, 0.85; 95% CI, 0.82–0.88) • Cancer population greater medication adherence variation based on greater interquartile range • Significant variation based on cancer type: thyroid more adherent and CRC/breast/prostate similarly adherent as general population • Factors affecting adherence: younger age (< 50), low income, rural, and treatment duration |
• 100% |
| Shin, 2012 [52] | • 92.7% of cancer survivors reported taking mediation regularly at all times; 73% of non-cancer comparison group reported taking medication regularly at all times • Cancer survivors were significantly more likely to report full adherence (aOR = 3.45; 95% CI: 2.08–5.73) • Subgroup analyses by cancer stage showed patients w/in situ or local tumors tended to report full adherence & very good perceived BP control (but no statistical significance by trend analysis) |
• 100% |
| Other CVD-related comorbidities | ||
| Cheung, 2013 [53] | • Among those that received a statin after discharge, 42 and 39% of CS and NCP, respectively, were adherent to therapy in 1997–1998 in contrast to 55 and 54%, respectively, in 2007–2008 (P < 0.001) • Of pts. prescribed a beta-blocker and all 3 medications, only NCP became increasingly adherent to therapy between 1997 and 2004 • Adherence to ACEIs/ARBs remained unchanged throughout the study period • Compared to NCP, more survivors received statins (38 vs. 31%) and b-blockers (67 vs. 59%), but fewer underwent bypass surgery (1.5 vs. 2.8%) after MI • Comorbidities (e.g., depression. lung disease) and demographics (advanced age, female) were associated w/ underuse of preventive care among survivors when compared to NCP |
• 100% |
Abbreviations:aOR adjusted odds ratio; CI confidence interval; CLL chronic lymphocytic leukemia; CML chronic myeloid leukemia; CNS central nervous system; CRC colorectal cancer; CVD cardiovascular disease; D-in-D difference in difference; GERD gastroesophageal reflux disease; GI gastrointestinal; OR odds ratio; MM multiple myeloma; MPR medication possession ratio; NHL non-Hodgkin lymphoma; NR not reported; PDC proportion of days covered; Pro prospective; PSM propensity score matching; Retro retrospective; SLL small lymphocytic leukemia