Adherence Clinic
1 Study Details
1.1 Study title
Pharmacist Interventions to Improve Specialty Medication Adherence: A Randomized Controlled Trial
1.2 Background
The effectiveness of specialty medications in complicated clinical conditions depends on adherence to therapy. Patient-tailored adherence interventions may be able to improve adherence in non-adherent patients.
1.3 Objectives
Primary Objective
- Assess effectiveness of patient-tailored intervention on improving 8-month PDC
Secondary Objectives
- Describe the rates and reasons for non-adherence
1.4 Methods
Single center, pragmatic, randomized controlled trial of usual care compared with usual care plus patient-tailored adherence interventions.
Patients were enrolled May 10, 2019 through August 10, 2021
Patients randomized to the intervention arm undergo a baseline assessment to clarify reasons for non-adherence and subsequently receive patient-tailored interventions based on their specific reasons
438 patients enrolled and trial will be ongoing from 10 May 2019 to the first half of 2020 with 8 months of follow-up for each patient.
Primary outcome: PDC calculated at 8 months post-enrollment
1.4.1 Exclusion Criteria
- PDC > 90% in previous 4 months or previous 12 months.
The PDC for the exclusion criteria was calculated in order to enrich the sample for non-adherent patients. The baseline PDC secondary outcome was calculated independently and uses the same algorithm as used to calculated the prospective PDC outcome. Due to the slightly different methods, some patient’s baseline PDCs are greater than 90%.
1.5 Outcomes
6, 8, and 12 month post-enrollment follow-up PDC
12 month pre-enrollment baseline PDC
Baseline Assessment Results
1.6 PDC Calculations
Medication adherence is estimated by calculating the proportion of days covered (PDC) from participants’ fill data from the electronic healthcare record.
Unlike other adherence estimates such as medication possession ratio, PDC accounts for oversupply and cannot be greater than 100%
A PDC of 1 indicates perfect adherence while a PDC of 0 indicates no use of medication.
\(PDC=\frac{\text{Sum of days covered in timeframe}}{\text{Number of days in time frame}}\)
Days covered within a time frame is a term used to indicate availability of a prescribed daily dose on a given day.
The availability of medication is tracked using a moving array of each day’s supply that accounts for overfills by moving extra medication within a fill period to the start of the first exhaustion date of the given medication
Oversupply is truncated at the end of the time frame and each day in the denominator is limited to have a maximum of 1 day’s supply.
For this study, the time frame is defined as the time period from the start of the first fill to the first day of the last fill.
Three different time-frames were specified for PDC calculations in this analysis
12 month retrospective baseline PDC: The time frame starts at the first medication fill within 1 year before trial enrollment and ends at the start of the last fill prior to trial enrollment
6, 8, and 12 months prospective PDC: The time frame starts at the first medication fill after trial enrollment and ends at the start of the last fill before 6, 8, or 12 months after trial enrollment.
2 Descriptive Statistics
2.1 Demographics and Characteristics
Demographics and characteristics | ||
N |
N=439 |
|
---|---|---|
Age | 439 | 40 53 64 (51 ±18) |
Sex | 439 | |
Male | 32% (140) | |
Female | 68% (299) | |
Race | 439 | |
White | 82.0% (360) | |
Black or African American | 13.4% ( 59) | |
Other | 2.1% ( 9) | |
NA | 2.5% ( 11) | |
Insurance | 439 | |
Commercial | 58.1% (255) | |
Medicare | 34.9% (153) | |
Medicaid | 7.1% ( 31) | |
None | 0.0% ( 0) | |
Other | 0.0% ( 0) | |
Medication Route | 439 | |
Injectable | 70% (307) | |
Oral | 30% (132) | |
Duration of Therapy | 439 | |
< 1 year | 33.0% (145) | |
>= 1 year | 66.5% (292) | |
NA | 0.5% ( 2) | |
Clinic | 439 | |
Adult Misc | 13.0% ( 57) | |
Adult Rheumatology | 34.6% (152) | |
Lipids | 17.1% ( 75) | |
MS | 19.6% ( 86) | |
Pediatric | 7.1% ( 31) | |
Pulmonary | 8.7% ( 38) | |
Clinic Level | 439 | |
High | 25.3% (111) | |
Medium | 33.3% (146) | |
Low | 41.2% (181) | |
NA | 0.2% ( 1) | |
Patient portal use | 439 | |
No | 33% (143) | |
Yes | 67% (296) | |
Baseline PDC 12m | 439 | 0.78 0.87 0.90 (0.81 ±0.12) |
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD. N is the number of non-missing values. Numbers after proportions are frequencies. |
3 Reasons for Non-adherence
The reasons for the non-adherence for the patients that participated in the randomized trial and the reasons for the misidentified non-adherent patients (none of which are in the RCT data) are displayed below.
3.1 Non-adherent Patients
3.1.1 Total Occurrences - Non adherent
The table gives the total number of occurrences for each non-adherence reason, but does not account for patients having intersections of multiple reasons.
Count (n= 299) | |
---|---|
Financial | 8 (2.7%) |
Clincial | 25 (8.4%) |
Health Literacy or comprehension | 19 (6.4%) |
Memory | 82 (27.4%) |
Unreachable | 60 (20.1%) |
Unresponsive | 32 (10.7%) |
Pharmacy/Clinic Error | 15 (5%) |
Social Issues | 23 (7.7%) |
No known reasons | 35 (11.7%) |
3.1.2 Upset plot - Non adherent
The upset plots are an alternative to a venn diagram and can be helpful when a set size is large. This upset plot gives the total number of occurrences for each non-adherence reason in the bottom left corner of the figure and is labeled “set size”. The “intersection size” graph on the top of the figure indicates the total number of occurrences for every intersection between the different reasons. The intersection is indicated by the dots at the bottom portion of the figure. The figure is not exhaustive and excludes low count intersections.
3.2 Misidentified Patients
775 patients were flagged as non-adherent when there was a reason for their non-adherence - these are referred to as “misidentified patients”. Two of misidentified patients were randomized into trial, but they were randomized before the cutoff date and were excluded. The following tables and charts summarize the count and patterns of the misidentified non-adherence reasons.
3.2.1 Total Occurences - Misidentified
The table gives the total number of occurrences for each non-adherence reason, but does not account for patients having intersections of multiple reasons.
Count n=(775) | |
---|---|
Clinical | 250 (32.3%) |
Non-VUMC fill | 136 (17.5%) |
Medication discontinuation | 167 (21.5%) |
Drug dosage form incongruency | 29 (3.7%) |
Temporary insurance laspse | 54 (7%) |
Switched to alternate GPI of same med | 87 (11.2%) |
No longer seeing VUMC | 16 (2.1%) |
Held for pandemic | 9 (1.2%) |
Other | 45 (5.8%) |
Delay in starting therapy | 1 (0.1%) |
Out of country | 0 (0%) |
3.2.2 Upset plot - Misidentified
The upset plots are an alternative to a venn diagram and can be helpful when a set size is large. This upset plot gives the total number of occurrences for each non-adherence reason in the bottom left corner of the figure and is labeled “set size”. The “intersection size” graph on the top of the figure indicates the total number of occurrences for every intersection between the different reasons. The intersection is indicated by the dots at the bottom portion of the figure. The figure is not exhaustive and excludes low count interestions.
3.3 Reasons for non-adherence by clinic
3.3.1 Barplot
3.3.2 Heatmap
4 Randomized Pharmacist Intervention
4.1 Descriptive Statistics
4.1.1 Interventions
A total of 355 interventions were performed on 190 patients (29 out of the 219 patients in the intervention group did not have interventions). The distribution of the number of interventions per patient in the intervention group is displayed below.
Interventions per patient | ||
N |
N=219 |
|
---|---|---|
Intervention Count | 219 | 1.0 1.0 2.0 (1.6 ±1.4) |
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD. N is the number of non-missing values. |
4.1.2 Contact attempts
Contacts per patient in treatment group | ||
N |
N=219 |
|
---|---|---|
Contacts per patient | 219 | 2.0 5.0 10.0 ( 6.7 ± 5.6) |
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD. N is the number of non-missing values. |
Total count of each contact type | ||
N |
N=1475 |
|
---|---|---|
Contact type | 1475 | |
Mailed letter | 3.3% ( 49) | |
Phone call- Left voicemail | 34.0% (502) | |
Phone call- No voicemail or contact | 17.1% (252) | |
Phone call- Spoke to patient | 34.2% (504) | |
Sent email | 4.8% ( 71) | |
Sent MHAV message | 6.6% ( 97) | |
N is the number of non-missing values. Numbers after proportions are frequencies. |
4.2 Outcomes
4.2.1 Post-enrollment PDC
4.2.1.1 Table
Prospective PDC Measurements | ||||
N |
Usual Care N=220 |
Intervention N=219 |
P-value |
|
---|---|---|---|---|
Baseline PDC 12m | 439 | 0.78 0.86 0.89 (0.81 ±0.12) | 0.78 0.87 0.90 (0.82 ±0.12) | 0.21 |
Prospective 6mo PDC | 397 | 0.76 0.90 0.98 (0.84 ±0.17) | 0.84 0.95 1.00 (0.90 ±0.13) | 0.003 |
Prospective 8mo PDC | 401 | 0.75 0.88 0.97 (0.83 ±0.17) | 0.84 0.94 0.99 (0.89 ±0.13) | <0.001 |
Prospective 12mo PDC | 402 | 0.72 0.87 0.95 (0.82 ±0.17) | 0.82 0.93 0.98 (0.88 ±0.13) | <0.001 |
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD. N is the number of non-missing values. Test used: Wilcoxon test . |
4.2.1.2 Density plots
5 8 Month PDC Outcome
5.1 Univariate
Prospective 8 Month PDC | ||||
N |
Usual Care N=220 |
Intervention N=219 |
P-value |
|
---|---|---|---|---|
Prospective 8mo PDC | 401 | 0.75 0.88 0.97 (0.83 ±0.17) | 0.84 0.94 0.99 (0.89 ±0.13) | <0.001 |
a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. x ± s represents X ± 1 SD. N is the number of non-missing values. Test used: Wilcoxon test . |
5.2 Ordinal logistic regression
5.2.1 Visualization
5.2.2 Table
95% Confidence interval
|
||||
---|---|---|---|---|
Variable | Odds Ratio | Lower | Upper | p-value |
Treatment group (Usual care reference) | ||||
Intervention | 1.82 | 1.28 | 2.59 | <0.001 |
12 Month Baseline PDC | ||||
Per 10 unit increase | 1.43 | 1.23 | 1.65 | <0.001 |
Age | ||||
Per 10 year increase | 1.13 | 0.97 | 1.31 | 0.111 |
Administration method (Injectable reference) | ||||
Oral | 1.25 | 0.78 | 2.01 | 0.361 |
Sex (Male reference) | ||||
Female | 1.07 | 0.71 | 1.60 | 0.746 |
Race (White reference) | ||||
Black or African American | 1.50 | 0.88 | 2.56 | 0.134 |
Other | 2.92 | 0.82 | 10.36 | 0.098 |
Duration of treatment (Less than one year reference) | ||||
Greater than or equal to 1 yearr | 1.24 | 0.83 | 1.85 | 0.302 |
Insurance (Commercial reference) | ||||
Medicare | 0.97 | 0.62 | 1.52 | 0.901 |
Medicaid | 1.22 | 0.50 | 2.97 | 0.661 |
Clinic (Rheumatology reference) | ||||
Adult Miscellaneous | 1.61 | 0.91 | 2.87 | 0.104 |
Lipids | 2.11 | 1.21 | 3.67 | 0.008 |
Multiple Sclerosis | 2.15 | 1.24 | 3.70 | 0.006 |
Pediatric | 2.09 | 0.75 | 5.84 | 0.158 |
Pulmonary | 1.35 | 0.65 | 2.82 | 0.420 |
Online portal use (Inactive reference) | ||||
Active | 1.13 | 0.76 | 1.67 | 0.545 |
5.3 8 month PDC by treatment group and clinic
5.3.1 Median difference in PDC pre and post-intervention by clinic
Clinic | Usual Care | Intervention |
---|---|---|
Adult Rheumatology | 0.02 (n=78) | 0.07 (n=74) |
Adult Misc | 0.03 (n=32) | 0.09 (n=25) |
MS | 0.09 (n=39) | 0.1 (n=47) |
Lipids | 0.08 (n=39) | 0.09 (n=36) |
Pulmonary | 0.05 (n=18) | 0.09 (n=20) |
Pediatric | 0.04 (n=14) | 0.07 (n=17) |
All | 0.06 | 0.09 |
2.2 Social Determinants of Health
N=439