Table 1.
Factors associated with adherence and persistence to active cancer treatment in older adults diagnosed with cancer
| Author, publication date (reference) | Which cancer treatments were included in the study? | Definition of non-adherence used or adherence/non-persistence used or persistence | Measurement of non-adherence/ non-persistence | Adherence /persistence rate | Statistical analysis used to examine factors associated with non-adherence /non-persistence | Which variables were included in the statistical analysis? | Factors associated with non-adherence (−) or higher adherence (+) | Factors associated with non-persistence (−) or higher persistence (+) |
|---|---|---|---|---|---|---|---|---|
| Barcenas et al. [36] | Chemotherapy | Non-adherence: having received one to three cycles of anthracyclines. Adherent: having received four or more cycles of anthracyclines | Claim codes in the administrative databases | Adherence rate: 83% | Logistic regression analysis | Age at diagnosis, race, marital status, educational level, poverty level, SEER region, year of diagnosis, lymph node involvement, tumour size, tumour grade, PR and ER receptor status, surgery type, Charlson comorbidity index, radiation therapy and number of hospitalizations | Age >75 years (−), black race (−), unmarried status (−), two different SEER-regions (−), those diagnosed in 2000 or earlier (−), number of hospitalizations (more hospitalizations had larger impact on non-adherence) (−) | NA |
| Barron et al. [37] | Tamoxifen (hormonal therapy) | Tamoxifen non-persistence was defined as 180 consecutive days of no tamoxifen supply after the index date (=first prescription) without alternative hormonal therapy during that time | Prescription refill data | Persistence rate: 77.9% at 1 year of treatment and 64.8% at 3.5 years of treatment | Cox proportional hazard regression analysis | Variables in univariate analysis with p< 0.1 were selected in the multivariable model and included age, types of prescription drug usage, number of having dementia/Parkinson disease, mean number of pharmacological agents per month | Age >75 compared with 45–54 years (−), using antidepressant medication at tamoxifen initiation (−), and having dementia/Parkinson disease (−), greater than one pharmacological agents per month a year before tamoxifen initiation (+) | |
| Demissie et al. [38] | Tamoxifen (hormonal therapy) | Women who were taking tamoxifen were classified at the second follow-up interview as either still taking tamoxifen (yes) or no longer taking tamoxifen (no) | Self-report during a telephone follow-up interview, questions not specified | Adherence: 85% at 21 months after surgery for breast cancer follow-up | Logistic regression analysis | All study variables were included in one model and then removed if not contributing. Two models were run: tamoxifen use at follow-up as outcome, and tamoxifen discontinuation at follow-up as outcome (n = 26, model underpowered) | No factor was associated with discontinuation of tamoxifen. Age (younger age +), stage 2 (+), ER positive status (+) and number of physicians (higher number +) and excellent ability (+) to communicate were all associated with tamoxifen use | |
| Dobie et al. [39] | Chemotherapy | Adherence: having received 5 months/cycles (one cycle a month) of chemotherapy within 9 months of diagnosis (liberal definition) and having received 6 months/cycles (one cycle a month) of chemotherapy within 9 months of diagnosis (conservative definition) | Claim codes in the administrative databases | Adherence rate using a conservative definition and full study sample: 78% | Logistic regression analysis | Race, age, sex, ethnicity, marital status, location of residence, and age-and race-specific household income and SEER registry were included in all models plus variables with P< 0.09 or those that significantly improved model fit | older age (−), female (−), readmission to hospital (−), recurrence of cancer (−) were associated with lower chemotherapy completion rates | |
| Fesinmeyer et al. [40] | Radiation therapy (RT) | Complete course of radiation: at least 30 treatments for those who did not have surgery before RT, at least 25 treatments for those who had prior surgery. An interruption or gap was defined as lapses of >4 but <31 days between RT treatments | Claim codes in the administrative databases | 70.4 of surgical patients and 52% of nonsurgical patients completed RT without interruptions/gaps | Logistic regression analysis, a separate model was calculated for each of the five tumour sites (larynx, nasal cavity, oral cavity, pharynx and salivary gland) | Each model included the receipt of surgery relative to radiation (yes/no and within 30 days), tumour stage, comorbidity, age, sex, race, urban versus rural residence | For oral cavity tumours: surgery within 30 days before RT (+), Charlson of 0(+), not chemo (+). For pharynx: surgery within 30 days of RT (+) and no chemo (+) and regional tumour (+). For laryngeal: surgery within 30 days of RT (+), no chemo (+), local tumours (+) and Charlson of 0 (+). For nasal cavity or salivary gland tumour: surgery within 30 days (+) | |
| Fink et al. [41]a | Tamoxifen (hormonal therapy) | Self-reported no longer taking tamoxifen, regardless of reason for stopping at 3, 6, 15 and 27 months after breast cancer surgery | Self-reported use during telephone interviews | Adherence: 83% at 1 year and 79% at 2 years of treatment | Logistic regression analysis | Predictors that were significant in univariate analyses were selected for inclusion as well as confounders not further specified | Decision balance scale score (having neutral or negative beliefs about the value of tamoxifen (−)) and number of positive nodes (−) | |
| Guth et al. [42]b | Hormonal therapy | Patients were divided into subgroups: those who did not initiate therapy (including those for whom therapy was not recommended/ was recommended but never began/refused) and those who initiated therapy (into discontinuation due to death/breast recurrence and/or distant metastasis, serious medical reasons other than breast cancer, therapy adverse effects, and other reasons) | Data were collected from the charts of follow-up consultations during which patients were asked about the treatments | Of the 325, 287 initiated endocrine therapy and One hundred and ninety-one of 287 (66.6%) completed 5-year therapy. Of the 96 who discontinued therapy, 31 were non-adherent (10.8%) | Logistic regression analysis | Only univariate analysis was conducted | Location of follow-up (GP follow-up (−)) | |
| Guth et al. [43]b | Hormonal therapy | Patients were divided in subgroups: those who did not initiate therapy (including those for whom therapy was not recommended/ was recommended but never began/refused) and those who initiated therapy (including those who completed 5 year therapy, those who completed >5 years, and those who discontinued due to drug-related side-effects and those who discontinued for other reasons such as death/recurrence/other serious medical reasons than breast cancer) | Data were collected from the charts of follow-up consultations during which patients were asked about the treatments | Non-persistence rate 37/400 (9.3%) | Descriptive analysis | NA | Of the 37 who were non-persistent, 24 discontinued because of side-effects, and 13 for other reasons including lack of motivation (5), lack of faith in therapy (2), misinformation by physician (2), errors regarding length of therapy (1), insurance reasons (1), denial of cancer diagnosis (1) and alcohol dependency/ psychiatric illness (2) | |
| Guth in press et al. [44]b | Hormonal therapy | A patient was classified as compliant when she started with the treatment. A patient was classified as persistent when they took their medication for at least 36 months |
Data were collected from the charts of follow-up consultations during which patients were asked about the treatments | In the 80+ group, 87% were compliant and in the 60–79 group 95.5% were compliant. In the group 80+, 83% were persistence and in the group 60–79 88% were persistent. | Descriptive analysis | NA | Of those in the 80+ non-persistent, 13% were non- persistent due to side-effects and 4% for other reasons (2 lack of motivation). Of those aged 60–79, 7% were non-persistent due to side-effects and 5% due to other reasons (nine lack of motivation /resistance, one misinformation by physician, and two alcohol dependency/ psychiatric disease. In the older group, medications were more often discontinued by the physician for serious side-effects | |
| Hoskin et al. [45] | Radiation therapy | No definition provided | Not described | Non-adherence rate is 17/322 | Descriptive analysis | NA | Seventeen patients were non-adherent: three refused to wear the mask needed for the treatment, one was hospitalized for reasons not related to treatment, one was hospitalized for adverse effects of treatment and for ten no reason was defined | |
| Kimmick et al. [46] | Hormonal therapy | Prescription rate: at least one pharmacy filled prescription for a hormonal therapy agent within 1 year of diagnosis. Adherence: a Medication Possession Ratio (MPR) >80%. MPR is defined as the total days covered by the medication/total days needing the medication. Non-persistence = a gap of ≥90 days between medication refills |
Using prescription fill and refill data | Rate of prescription fill was 64% and 70% for those with hormone receptor-positive tumours. The mean MPR was 0.75. Adherence rate: 60% had a MPR of >80% during the first year after the initial prescription. The persistence rate was 80% | Logistic regression analysis | Age, race, comorbidity, number of prescription medications, stage, hormone receptor status, type of surgery, adjuvant chemo received, RT received, urban or rural residence, type of hospital. A separate model for adherence and persistence was calculated | Marital status (non-married (+). | Marital status (non-married +), Charlson comorbidity index of 3 compared with 0 (+), having a regional stage compared with local stage (+). |
| Lash et al. [47]a | Tamoxifen (hormonal therapy) | Self-reported discontinuation of tamoxifen, regardless of reason for stopping at 3, 6, 15, 27, 29, 51 and 63 months after breast cancer surgery | Self-reported use of tamoxifen during telephone interviews | After 5 years, 100 women (31%) had stopped taking Tamoxifen, 16 of those had restarted in the 5 year period | Cox proportional hazard regression analysis | Age, sex, estrogen receptor (ER) status, presence of tamoxifen side-effects, and number of prescription drugs | More prescription medications at baseline (−), new medication during follow-up (−). Severe side-effects at baseline and during follow-up (−). Positive views of tamoxifen (+) | |
| Lau et al. [48] | Chemotherapy and surgery | No definition was provided | Not reported | Twenty-five of 36 (69.4%) were adherent | Not reported, seems descriptive analysis only | NA | For two patients who received only one cycle the reasons are lack of immediate treatment effect, for nine patients who had completed chemo but refused the surgery they had a misconception that after chemo and they had been told their tumour had shrunk, because they were no longer in pain they could wait and perhaps avoid the surgery altogether. | |
| Neugut et al. [49] | Aromatase inhibitors (hormonal therapy) | Non-persistence: a supply gap of minimum 45 days and with no subsequent refills before the end of the study period. Non-adherence: a Medication Possession Ratio of less 80% | Using prescription refill data | Of those aged ≥65 , 24.7% were non-persistent and 8.9% were non-adherent over the 2-year study period | Logistic regression analysis | All study variables (out of pocket costs, number of other prescriptions, type of specialist, age, race, marital status, income, region of United States, and comorbidities) were included. Two models were calculated: one for adherence and one for persistence | A co-payment of $30–89.99 and $90 and more (−) | A co-payment of $30–89.99 and $90 and more (−). Age 84 and over (−), prescription of AI written by primary care specialist or different specialist (−), and increased number of prescriptions (−) |
| Owusu et al. [50] | Tamoxifen (hormonal therapy) | Tamoxifen discontinuation was operationalized as ever discontinuing tamoxifen for >60 days during the initial 5-year tamoxifen prescription | Prescription refill data | Forty-nine percent discontinued Tamoxifen before the 5 year completion | Cox proportional hazard regression analysis | All variables that were significant predictors of tamoxifen discontinuation at P< 0.10 were included in model which included age at diagnosis, race, lymph node involvement, estrogen and progesterone receptor status, and primary therapy received | Aged 75–80 or aged ≥80 compared to those <70 years, ER indeterminate status vs. ER+ (−), having received a breast-conserving surgery without radiation (−) | |
| Partridge et al. [51]c | Chemotherapy/molecular-targeted therapy | Non-persistence: coming off therapy without completing the protocol specified treatment. Non-adherence, if fewer than 80% of doses expected were recorded by the MEMS. A missed dose of capecitabine was defined as no redosing within 20 h of the previous dose, when another dose was planned as per protocol. A dosing violation was defined as taking a dose <8 h or >16 h but <20 h from the previous dose. | MEMS | Eighty-three of patients were persistent. Average adherence across all cycles was 78% | Logistic regression analysis | Age, ethnicity, performance status, tumour size, hormone receptor status | Node-negative disease (−), received mastectomy (−) | The 26 (17%) who did not complete the protocol: 17 had toxicity/adverse effects or complications, 5 withdrew from the study and 2 had disease progression/ relapse and 2 died |
| Partridge et al. [52] | Tamoxifen (hormonal therapy) | Adherence: the proportion of eligible days during the 365 days following the first tamoxifen prescription. Patients with ≥80% days covered is adherent. | Prescription refill data | The overall adherence rate during the first year was 87%. Seventy-seven percent had filled prescriptions to cover ≥80% of the year and were classified as adherent | Logistic regression analysis | All variables were included in multivariable model which included age, race, surgery, visit to oncologist in past year, Charlson Comorbidity Score, other prescription drug use, number of outpatient services use and days hospitalized in the first year | Age 85 and older (−), non-White race (−), having had a mastectomy (−), having seen a seen a medical oncologist before starting tamoxifen (+), increasing Charlson scores (+). | |
| Regnier Denois et al. [53] | Chemotherapy/molecular-targeted therapy | Patient reported non-use of treatment | Focus group and individual interviews | Rate is NR, the majority of patients indicated that they never had forgotten their treatment | NA | NA | Patients reported that a change in their daily routine (such as outing in town, visiting friends or going on holiday) was associated with forgetting their medication (−), side-effects (−), not understanding the prescription (−). Timing of dosages was adjusted for convenience reasons | |
| Ruddy et al. [54]c | chemotherapy/molecular targeted therapy | Persistence with CMF: being prescribed six cycles of at least one of the three CMF drugs. Adherence to oral cyclophosphamide was calculated using the number of doses taken according to the medication calendars divided by the number of doses prescribed. Non-adherent was <80% of expected doses (11 or fewer of the 14 doses per cycle) |
Self-report using medication calendars and case-report forms filled out by study investigators | Sixty-five percent were persistent with CMF. Adherence with cyclophosphamide was 95% | Logistic regression analysis | The significant univariate variables were entered in a stepwise forward model predicting persistence which included only node status and hormone receptor status. A separate model was constructed to examine which grade 3 and 4 side-effects were associated with persistence, the final model included fatigue, vomiting and febrile neutropenia | Non-adherence was not modelled due to the small number of patients who were classified as non-adherent | Node negativity (−) and hormone receptor positive tumours (−), fatigue (−)and febrile neutropenia (−) |
| Shaheen et al. [55] | Luteinizing hormone-releasing hormone agonist (LHRH) | Non-compliance: missing 1 or more injections. Delay: more than 2 weeks after the scheduled time for the injection | Data collected from chart | Fifty-six perecnt were adherent, and 24% had a delay for one or more injections | Descriptive analysis | NA | Reasons for missing appointments were patients were confused about the treatment, long waiting times in clinics, having to travel a long distance to the clinic, clinic was closed due to holidays, and pain and bleeding at injection site | |
| Winterhalder et al. [56] | Chemotherapy/molecular-targeted therapy | Adherence: fully adherent to recommended dosage and intake interval for the duration of treatment | Self-reported intake of capecitabine using diaries which were completed daily | Ninety-one percent were fully adherent. The adherence rate among those with no adverse effects was 95%, and for those with three or more side-effects the adherence was 66.7%) | Not reported | Not reported. | The reasons for making mistakes included forgetting treatment (n = 9), side-effects (n = 4), and misunderstanding instructions (n = 3) There was a trend that those with less adverse events were more adherent (only P = 0.07 provided) |
|
| Ziller et al. [57] | Tamoxifen and anastrazole (hormonal therapy) | A patient was adherent when self-reported and if an MPR of ≥80% was achieved | Self-reported adherence measured using a questionnaire (questions not specified). Prescription checks were done using the charts. | Self-reported adherence 100%, MPR adherence 80% for tamoxifen and 69% for anastrazole using prescription information from charts | Logistic regression analysis | Only univariate models were calculated. Factors examined included age, job training, family risk, having children, tolerability to treatment, medication interruption, side-effects and quality of life | There was no significant predictor for adherence to tamoxifen or anastrazole. |
aThese two publications used data from the same prospective observational cohort study.
bIn these three publications part of the study sample selected from the clinical database is overlapping.
cThese two publications used data from the same companion study of a randomized clinical trial.
RT, radiation therapy; MEMS, microelectronic monitoring system; NA, not applicable; NR, not reported; CMF, cyclophosphamide methotrexate 5-fluorouracil.