Enhancing Medication Adherence in Multiple Sclerosis Patients
Medication adherence among persons with
Multiple Sclerosis;
From observation to intervention
Team members
:
Efrat Neter
1
, Efrat Esterkin-Hubner
2
, Anat Wolkowitz
2
, Lea Glass-Marmor
2
, Ariel
Miller
2,4
1
Ruppin Academic Center, Israel
2
Multiple Sclerosis Center & Department of Neurology, Carmel Medical Center, Haifa, Israel
2, 3
Rappaport Faculty of Medicine & Research Institute, Technion Institute of Technology, Haifa, Israel
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Background
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What is MS?
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What is adherence?
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Disease-Modifying Therapies (DMTs) for persons with relapsing-remitting multiple sclerosis
(PwRRMS); Advantages & challenges
•
Observation
stage:
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Adherence to DMT and reasons for non-adherence
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Identify useful/relevant theory
•
Intervention
stage
:
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Description of Intervention
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Acceptability, Feasibility and Efficacy
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Part I - background
M
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c
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A
chronic
autoimmune
disease of the central nervous system characterized by
inflammation, demyelination, and axonal degeneration.
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MS is a
heterogeneous, multifactorial, immune-mediated
disease that is
caused by complex gene–environment interactions.
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Several sub-types; heterogeneous clinical manifestations and course
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In most patients, reversible episodes of neurological deficits (known as
relapses) that usually last for days or weeks characterize the initial phases
of the disease (relapsing MS)
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Over time, the development of permanent neurological deficits and the
progression of clinical disability become prominent
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Onset: 20-40 years old; ~0.1% prevalence (geography and latitude
dependent)
4
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T
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s
(
D
M
T
s
)
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Modify
the
course
of MS through the immune system; available for
people with relapsing-remitting multiple sclerosis (RRMS)
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Prescription by physicians is determined by: safety, efficacy,
tolerability and QoL
•
Currently many options
5
Pharmacological effects, though,
depend (also) on medication taking
behavior
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(
D
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)
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DMTs - currently a mainstay of treatment strategies to persons with RRMS (PwRRMS),
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Effective
in terms of disease progression
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limit the number of relapses,
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prevent new lesion formation,
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decrease in neuropsychological issues,
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reduce the accumulation of disability
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slow progression of disease
.
•
Adherence to DMT associated with
•
improved quality of life,
•
fewer days of work loss,
•
reduced hospitalizations, emergency visits, outpatient visits,
•
reduced annual medical care costs at the societal level.
•
Adherence especially important in a chronic condition, when disease onset is at an early age, requiring
many years of treatment.
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(
D
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Need for DMT not seem clear in times of disease inactivity or
mild course (progression is unnoticeable to PwRRMS)
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Chronic
symptoms are not reduced
by DMTs
(other/additional medications address them)
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Benefits of treatment only accrue
long-term
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Adverse side effects are
immediate
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Adherence
- the extent of
correspondence
between
medication taking
behavior
and the
recommendations
made by the provider with respect to
timing,
dosage, and
frequency
Persistence
- staying on same medication/treatment.
Switching
– moving between medications.
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S
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R
ecent meta-analysis (
Nicholas et al., 2020
)
on oral DMT
adherence:
•
before one year of treatment,
20%
of PwRRMS were
not
taking it as prescribed (i.e., non-adherence),
•
one in four
PwRRMS discontinued treatment (i.e.,
non-persistence.
•
Rates of adherence to injectable DMT ranges
25-50%
within 1-5 years
.
•
Reasons for non-adherence - WHO model.
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In MS, most studies focused on social-economic or
therapy-related factor (e.g., administration modality)
factors
.
•
Reasons were both
intentional
and
non-intentional
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Part II –
Observation
Intervention Mapping (IM) approach –
structures the road towards intervention
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1.
Compared adherence rates by
•
various
measures/methods
[electronic
pharmacy records (MPR), patient-
reported scales, and electronic
medical device (EMD]
•
across
time
•
two
administration routes
of DMTs –
oral and self-injected
2.
Examine association between
measures of adherence.
Stage 1: Measuring adherence prospectively
Patient-reported yielded the
most variance; EMD – failure
(own device and pharma’s).
Moderate consistency across
time (within-person): 84%
agreement, Kappa=0.47, < 0.70
(=criteria in test-re-test)
No difference across modalities
Moderate-to-high % agreement
between measures:
80%
agreement (MPR & PRO, translating into
Kappa=0.37)
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1.
Adherence range: 63 - 66% (depends on modality, brand,
time)
2.
Medication perceptions
– the consistent predictor of
adherence (across times, modalities)
3.
Within-person variability
Stage 1: Measuring and predicting adherence prospectively –
key findings
Stage 1: Key
determinants
of DMT non-adherence and
non-persistence identified by the needs assessment
14
)
Main theoretical
framework
chosen:
Perceptions
and
Practicalities
Approach
(PAPA)
15
Horne, R., Cooper, V., Wileman, V., & Chan, A. (2019). Supporting adherence to medicines for long-term conditions: A perceptions and
practicalities approach based on an extended common-sense model. European Psychologist, 24(1), 82–96. https://doi.org/10.1027/1016-
9040/a000353
Perceptions and Practicalities Approach
(PAPA):
motivation
and
ability
as core intrinsic attributes for adherence.
16
Perceptions and Practicalities Approach –
a detailed conceptual map of adherence
.
Horne, R., Cooper, V., Wileman, V., & Chan, A. (2019). Supporting adherence to medicines for long-term conditions: A perceptions and
practicalities approach based on an extended common-sense model. European Psychologist, 24(1), 82–96. https://doi.org/10.1027/1016-
9040/a000353
Stage 2:
Identify Intervention Objectives
17
)
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The obvious: increase adherence.
•
Target would depend on power and N.
Stage 3:
Select or design practical applications to deliver
change methods
18
)
•
Meta-analyses (Conn et al., 2016, 2017) recommendations:
•
face-to-face interventions.
•
F
ocus on behavioral strategies and less on knowledge and beliefs.
•
Medication taking interventions among
PwMS
•
focused mostly on persistence or re-initiation, not on adherence.
•
the reported interventions were tailored, using either digital tools or
motivational
interviewing (MI)
, delivered either via telephone or face-to-face.
•
studies on adherence did not find the interventions efficacious or were very small (N).
Decision: f2f Motivational interviewing;
also include education component.
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)
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a
patient-centered
,
evidence-based
psychological counseling method
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aimed at exploring and resolving
ambivalent feelings and
perceptions
regarding behavior change.
•
has grown in use across diverse health settings in order to support
behavior change,
•
including medication adherence,
•
including
among individuals with MS.
20
Part III –
Intervention
Acceptability
,
Feasibility
and initial
efficacy
study (a pilot)
21
)
Carried among
identified non-adherent individuals
,
designed as
tailored to the specific reasons of non-adherence, aiming at
empowering PwRRMS.
RQs:
1.
Did the developed intervention increased adherence?
2.
If ‘Yes’, whether changes also took place in
•
medication habit
•
beliefs about medications.
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&
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Intervention development &
implementation
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)
1.
All PwRRMS in an observational study (n=230)
screened
for
eligibility.
2.
Enrolled if
eligible
and
agreed
.
•
Eligibility criteria
:
•
being prescribed oral/injectable DMT
(Fingolimod, Dimethyl Fumarate, Interferon
beta-1a and Glatiramer Acetate, Teriflunomide
)
for > 6 months
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identification as
non-adherent
by self-reports or medication claims
records.
•
Exclusion criteria
:
•
discontinuation of the medication on which non-adherence was
identified,
•
being non-Hebrew speaking
•
Decision to participate in the intervention was determined jointly by the
PwRRMS and the attending physician.
•
91 PwRRSM were identified as eligible, 60 enrolled (Visit 1), 52 completed
the intervention (Visit 2) and 46 also completed the 12-months follow-up.
230 screened
91 eligible
62 consented,
60 enrolled
52 completed
intervention
46 completed follow-up
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)
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quasi-experimental pretest posttest
and a follow-up assessment;
•
assumed a moderate degree of recruitment consent and retention;
•
Anticipating we may end up with 40 participants at follow-up, a
power
of 0.79 was estimated to be
sufficient to identify a difference of 0.45 standard deviation (effect size) at a 0.05 significance level.
•
IRB #NCT02488343; registration (ClinicalTrials.gov) IDCMC-14-0061-CTIL)
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P
sycho-education:
•
E
ducation
carried out by the
treating neurologist,
•
B
ehavioral
, utilizing Motivational
Interviewing (MI), carried out by a
health psychologist.
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Visit 1: the neurologist
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brief explanation on MS,
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review of the participant’s medical status (show PwMS’ recent MRI),
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a review of
scientific evidence supporting the benefit
s of
specific
medication taken by the participant (delayed progression of disability,
reduced proliferation of lesions, sustained cognitive ability),
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a discussion of potential
side effects
with a focus on those
experienced by the participant and
strategies
for reducing them.
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A pre-scheduled
telephone
booster
, 7-10 days later
.
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Missed doses analyzed,
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the importance of adherence
and participant's self-efficacy
were reinforced,
•
the main behavioral change
techniques (BCTs) agreed
upon in the previous session
(Visit 1) repeated.
•
Median time 11 minutes.
Visit #1,
MI
–
•
experiences of coping w/ MS,
•
goals and hopes
for life w/ MS,
•
pros and cons
for DMT use/non-
use/partial use,
•
cases of recent missed doses
reviewed
;
•
potential strategies
for medication
adherence (e.g., participants identified
personal high-risk situations of a missed
dose);
•
a
behavioral analysis
of a typical missed
dose;
•
coming up w/
ways of preventing
circumstances leading to a missed dose.
•
Median time 30 min.
Visit #2
, MI, ~20 min,
.....
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R
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P
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PwRRMS were predominantly women,
•
A
ssessed their health as below average (Mean =
1
.95 on a 5-point scale),
•
P
hysical disability (EDSS) was relatively low-to-moderate (Mean=2.78, SD=1.99, Median=2.50, IQR=1.00 –
4.00).
•
Mean MS
duration 8.80 years.
30
Recruitment (acceptability) and retention
in the intervention
•
91/230 identified, 62 consented, and 60 actually completed MI in first
visit
•
No difference between consenters and decliners in demographics
and clinical characteristics
•
N of sessions attended
associated with
•
low SES (more session – low SES)
•
affective states (more depression and anxiety), lower QoL, worse illness perceptions
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Significant effect,
d
=0.26
Non-significant effect,
d
=0.22
Paired comparisons
using Wilcoxon
Signed-Rank
non-
parametric
test
Auxiliary outcomes:
medication’s habit and beliefs and
rating of importance and efficacy
•
Habit and beliefs
:
No significant differences were found between at Visit 1 and
Visit 2 (
P
’s > .05).
•
Importance and efficacy ‘rulers’:
•
Significant differences in between
Visit
1 and phone booster;
•
non-significant differences between
Visit 1 and Visit 2
.
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C
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Intervention is
feasible
:
•
2/3 agreed,
•
~1/2 of those identified completed;
•
more retention among the worse-off psychologically
Need for psycho-social support
evident.
•
Efficacy
:
•
Adherence increased at 6 months, then reverted at 12 months (‘triangle effect’).
•
Needs augmentation/additional boosters; blended approach recommended
•
Small effect size, congruent with meta-a
na
lysis’ results.
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Utilized an intervention mapping approach. PAP
theoretical model.
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Long follow-up uncovered a fade-off.
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L
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•
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No control group (due to small N)
•
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Communication outside clinic was restricted by HMO; policies changed since COVID.
•
E
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,
•
just-in-time response to a decrease in medication adherence;
•
could be integrated into patient support programs of pharma companies.
•
N
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.
Q
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w
o
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o
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a
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s
a
n
d
n
e
e
d
s
.
•
Intervention addressed only patient and therapy-related factors and not healthcare system and
condition-related.
Personal Note: Long Road …
•
Work started 10 years ago
•
IRB, registration, …
•
Still producing publications
•
Satisfying contribution
38
Neter, E
. & Miller, A. (2023). Using an intervention mapping approach to improve
adherence to Disease-Modifying Treatment in Multiple Sclerosis.
International Journal of
Multiple Sclerosis Care, 25 (5).
doi:
10.7224/1537-2073.2022-018
.
Neter, E
., Glass-Marmor, L., Wolkowitz, A., & Miller, A., (2022).
Medication habits
among persons with multiple sclerosis.
Multiple Sclerosis and Related Disorders, 68,
104224.
doi.org/10.1016/j.msard.2022.104224
Neter
, E., Glass-Marmor, L., Haiien, L., & Miller, A. (2021). Concordance between
persons with Multiple Sclerosis and physician on medication effect and health status.
Patient Preference and Adherence,
15
, 939-943
.
doi
:
10.21203/rs.3.rs-45699/v2
Neter
, E., Glass-Marmor, L., Wolkowitz, A., Lavi, I., & Miller, A. (2021). Beliefs about
medication as predictors to medication adherence in a prospective cohort study among
patients with Multiple Sclerosis.
BMC Neurology,
21, 136.
doi
:
10.21203/rs.3.rs-45699/v1
.
Neter
, E., Wolkowitz, A., Glass-Marmor, L., Lavi, I., Ratzabi, S., Lejbkowicz, I., & Miller,
A. (2020). Multiple modality approach to assess adherence to medications across time in
Multiple Sclerosis
. Multiple Sclerosis and Related Disorders
, 40, 101951.
doi:
10.1016/j.msard.2020.101951
.
Thanks to our participants
Thank you for listening.
39
neter@ruppin.ac.il
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Examples to dimensions/factors:
1 - age, education, marital status, having kids.
2 – access to care, out-of-pocket,
3 – lack of symptoms, severity of symptoms, addiction
4 – method of administration (pills/injections/..), time
spent on trt, number of times/day,
5 – self care/management skills, efficacy, emotions,
perceptions …..
Adherence is multi-factorial
This study explores medication adherence among individuals with Multiple Sclerosis (MS), presenting insights from observation to intervention stages. It delves into the background of MS, adherence, Disease-Modifying Therapies (DMTs), and the challenges faced. The team identifies reasons for non-adherence and implements an intervention using the Intervention Mapping (IM) approach. The content emphasizes the importance of enhancing adherence to DMTs in individuals with relapsing-remitting MS to improve outcomes.
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Medication adherence among persons with Multiple Sclerosis; From observation to intervention Team members: Efrat Neter1, Efrat Esterkin-Hubner2, Anat Wolkowitz2, Lea Glass-Marmor2, Ariel Miller2,4 1 Ruppin Academic Center, Israel 2 Multiple Sclerosis Center & Department of Neurology, Carmel Medical Center, Haifa, Israel 2, 3 Rappaport Faculty of Medicine & Research Institute, Technion Institute of Technology, Haifa, Israel 1
Content Content from observation to intervention from observation to intervention Background What is MS? What is adherence? Disease-Modifying Therapies (DMTs) for persons with relapsing-remitting multiple sclerosis (PwRRMS); Advantages & challenges Observation stage: Adherence to DMT and reasons for non-adherence Identify useful/relevant theory Intervention stage: Description of Intervention Acceptability, Feasibility and Efficacy Intervention Mapping (IM) approach structured the process of design and implementation of intervention 2
Multiple sclerosis Multiple sclerosis A chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. MS is a heterogeneous, multifactorial, immune-mediated disease that is caused by complex gene environment interactions. Several sub-types; heterogeneous clinical manifestations and course In most patients, reversible episodes of neurological deficits (known as relapses) that usually last for days or weeks characterize the initial phases of the disease (relapsing MS) Over time, the development of permanent neurological deficits and the progression of clinical disability become prominent Onset: 20-40 years old; ~0.1% prevalence (geography and latitude dependent) 4
Disease Modifying Treatments (DMTs) Disease Modifying Treatments (DMTs) Modify the course of MS through the immune system; available for people with relapsing-remitting multiple sclerosis (RRMS) Prescription by physicians is determined by: safety, efficacy, tolerability and QoL Currently many options Pharmacological effects, though, depend (also) on medication taking behavior 5
Advantages Advantages of of Disease Disease- -Modifying Therapies (DMT) Modifying Therapies (DMT) DMTs - currently a mainstay of treatment strategies to persons with RRMS (PwRRMS), Effective in terms of disease progression limit the number of relapses, prevent new lesion formation, decrease in neuropsychological issues, reduce the accumulation of disability slow progression of disease. Adherence to DMT associated with improved quality of life, fewer days of work loss, reduced hospitalizations, emergency visits, outpatient visits, reduced annual medical care costs at the societal level. Adherence especially important in a chronic condition, when disease onset is at an early age, requiring many years of treatment. 6
Challenges Challenges in Disease Disease- -Modifying Therapies (DMT) Modifying Therapies (DMT) Need for DMT not seem clear in times of disease inactivity or mild course (progression is unnoticeable to PwRRMS) Chronic symptoms are not reduced by DMTs (other/additional medications address them) Benefits of treatment only accrue long-term Adverse side effects are immediate in 7
Medication taking behavior Medication taking behavior - - Definitions Definitions Adherence - the extent of correspondence between medication taking behavior and the recommendations made by the provider with respect to timing, dosage, and frequency Persistence - staying on same medication/treatment. Switching moving between medications. 8
Adherence and persistence rates in MS Adherence and persistence rates in MS Recent meta-analysis (Nicholas et al., 2020) on oral DMT adherence: before one year of treatment, 20% of PwRRMS were not taking it as prescribed (i.e., non-adherence), one in four PwRRMS discontinued treatment (i.e., non-persistence. Rates of adherence to injectable DMT ranges 25-50% within 1-5 years. Reasons for non-adherence - WHO model. In MS, most studies focused on social-economic or therapy-related factor (e.g., administration modality) factors. Reasons were both intentional and non-intentional 9
Part II Observation 10
Intervention Mapping (IM) approach structures the road towards intervention Step Tasks Based on Establish the extent of the non-adherence; Identify behavioural and environmental determinants associated with the non-adherence Literature review; Longitudinal observational study investigating predictors of non-adherence 1 Needs Assessment Identify expected outcomes and performance objectives for intervention; Establish targeted behavioral determinants Needs Assessment (stage 1); 2 Perceptions and Practicalities Approach (PAPA); Identify Intervention Objectives 3 Select or design practical applications to deliver change methods; Select theory and evidence-based intervention methods based on pre-identified determinants Literature review; Perceptions and Practicalities Approach (PAPA); Necessity-Concerns Framework (NCF); Motivational interviewing Theory-based methods and practical strategies 4 Integrate these practical applications into an organized program; Establish the format of the intervention; Draft and refine materials (consult with intended users) Patients input; Clinicians; Research team Develop intervention Identify intended users/targets; Develop indicators and measures for assessment; Evaluation plan 5 Methods Implementation and evaluation plan 6 Results Implementation 11
Stage 1: Measuring adherence prospectively 1. Compared adherence rates by various measures/methods [electronic pharmacy records (MPR), patient- reported scales, and electronic medical device (EMD] across time two administration routes of DMTs oral and self-injected Patient-reported yielded the most variance; EMD failure (own device and pharma s). Moderate consistency across time (within-person): 84% agreement, Kappa=0.47, < 0.70 (=criteria in test-re-test) No difference across modalities Moderate-to-high % agreement between measures: 80% agreement (MPR & PRO, translating into Kappa=0.37) 2. Examine association between measures of adherence. 12
Stage 1: Measuring and predicting adherence prospectively key findings 1. Adherence range: 63 - 66% (depends on modality, brand, time) 2. Medication perceptions the consistent predictor of adherence (across times, modalities) 3. Within-person variability 13
) Stage 1: Key determinants of DMT non-adherence and non-persistence identified by the needs assessment Barriers/ Facilitators to DMT adherence/persistence Determinant Concerns, necessity, harm, overtreatment (Horne et al., 2013; Neter et al., 2021; Thach et al., 2017) Medication beliefs Side effects Main theoretical framework chosen: Perceptions and Practicalities Approach (PAPA) Reduced quality of life (Bruce & Lynch, 2011( Treatment satisfaction Thach et al., 2017; also, not MS-specific, Barbosa et al., 2012 Affective states High levels of anxiety and depression (Bruce et al., 2010; Neter et al., 2021; Schoor et al., 2019) Memory Bruce et al., 2010; Horne et al., 2019 MS knowledge, self- efficacy Conn & Ruppar, 2017; Costa et al., 2015 14
Perceptions and Practicalities Approach (PAPA): motivation and ability as core intrinsic attributes for adherence. Horne, R., Cooper, V., Wileman, V., & Chan, A. (2019). Supporting adherence to medicines for long-term conditions: A perceptions and practicalities approach based on an extended common-sense model. European Psychologist, 24(1), 82 96. https://doi.org/10.1027/1016- 9040/a000353 15
Perceptions and Practicalities Approach a detailed conceptual map of adherence. Horne, R., Cooper, V., Wileman, V., & Chan, A. (2019). Supporting adherence to medicines for long-term conditions: A perceptions and practicalities approach based on an extended common-sense model. European Psychologist, 24(1), 82 96. https://doi.org/10.1027/1016- 9040/a000353 16
) Stage 2: Identify Intervention Objectives The obvious: increase adherence. Target would depend on power and N. 17
) Stage 3: Select or design practical applications to deliver change methods Meta-analyses (Conn et al., 2016, 2017) recommendations: face-to-face interventions. Focus on behavioral strategies and less on knowledge and beliefs. Medication taking interventions among PwMS focused mostly on persistence or re-initiation, not on adherence. the reported interventions were tailored, using either digital tools or motivational interviewing (MI), delivered either via telephone or face-to-face. studies on adherence did not find the interventions efficacious or were very small (N). Decision: f2f Motivational interviewing; also include education component. 18
) Motivational interviewing Motivational interviewing a patient-centered, evidence-based psychological counseling method aimed at exploring and resolving ambivalent feelings and perceptions regarding behavior change. has grown in use across diverse health settings in order to support behavior change, including medication adherence, including among individuals with MS. 19
Part III Intervention 20
) Acceptability, Feasibility and initial efficacy study (a pilot) Carried among identified non-adherent individuals, designed as tailored to the specific reasons of non-adherence, aiming at empowering PwRRMS. RQs: 1. Did the developed intervention increased adherence? 2. If Yes , whether changes also took place in medication habit beliefs about medications. 21
Methods, Stages Methods, Stages 4 4 & & 5 5 Intervention development & implementation 22
) Participants Participants 1. All PwRRMS in an observational study (n=230) screened for eligibility. 230 screened 2. Enrolled if eligible and agreed. Eligibility criteria: being prescribed oral/injectable DMT (Fingolimod, Dimethyl Fumarate, Interferon beta-1a and Glatiramer Acetate, Teriflunomide) for > 6 months identification as non-adherent by self-reports or medication claims records. Exclusion criteria: discontinuation of the medication on which non-adherence was identified, being non-Hebrew speaking Decision to participate in the intervention was determined jointly by the PwRRMS and the attending physician. 91 PwRRSM were identified as eligible, 60 enrolled (Visit 1), 52 completed the intervention (Visit 2) and 46 also completed the 12-months follow-up. 91 eligible 62 consented, 60 enrolled 52 completed intervention 46 completed follow-up 23
) Design and Ethics Design and Ethics quasi-experimental pretest posttest and a follow-up assessment; assumed a moderate degree of recruitment consent and retention; Anticipating we may end up with 40 participants at follow-up, a power of 0.79 was estimated to be sufficient to identify a difference of 0.45 standard deviation (effect size) at a 0.05 significance level. IRB #NCT02488343; registration (ClinicalTrials.gov) IDCMC-14-0061-CTIL) 24
Procedure Procedure Telephone booster, Identification Visit 1, Baseline Visit 2, Reinforcement & conclusion of intervention, 6 months after baseline 7-10 days after baseline Education & Motivational interviewing. Psycho-education: Education carried out by the treating neurologist, Behavioral, utilizing Motivational Interviewing (MI), carried out by a health psychologist. Motivational interviewing. 25
Procedure Procedure educational educational content of intervention content of intervention Visit 1: the neurologist brief explanation on MS, review of the participant s medical status (show PwMS recent MRI), a review of scientific evidence supporting the benefits of specific medication taken by the participant (delayed progression of disability, reduced proliferation of lesions, sustained cognitive ability), a discussion of potential side effects with a focus on those experienced by the participant and strategies for reducing them. 26
Procedure Behavioral intervention Behavioral content of A pre-scheduled telephone booster, 7-10 days later. Missed doses analyzed, the importance of adherence and participant's self-efficacy were reinforced, the main behavioral change techniques (BCTs) agreed upon in the previous session (Visit 1) repeated. Median time 11 minutes. Visit #1, MI experiences of coping w/ MS, goals and hopes for life w/ MS, pros and cons for DMT use/non- use/partial use, cases of recent missed doses reviewed; potential strategies for medication adherence (e.g., participants identified personal high-risk situations of a missed dose); a behavioral analysis of a typical missed dose; coming up w/ ways of preventing circumstances leading to a missed dose. Median time 30 min. Visit #2, MI, ~20 min, ..... 27
) Materials Materials Main outcome: Medication adherence (ProMAS), assessed at baseline (Visit 1), 6 and 12 months after baseline. 18-item of adherence behaviors, (e.g., I have never changed my medicine use myself , When I am away from home, I occasionally do not take my medicines ). Internal reliabilities ? = 0.83, 0.82 and 0.83 at Visit 1, Visit 2, and follow-up, respectively. Expanded Disability Status Scale (EDSS) Other PPOs: medication habits, beliefs about medication, illness perceptions, affective states, and quality of life. Psychologist s perception of the importance the participant attached to medication adherence and perceived efficacy (importance and efficacy rulers within MI), ranging 1-10. Demographic details (age, sex, education, social-economic status, self-rated health), retrieved from the observational study. 28
Results, Stage Results, Stage 6 6 29
Participants Participants characteristics characteristics PwRRMS were predominantly women, Assessed their health as below average (Mean = 1.95 on a 5-point scale), Physical disability (EDSS) was relatively low-to-moderate (Mean=2.78, SD=1.99, Median=2.50, IQR=1.00 4.00). Mean MS duration 8.80 years. 30
Recruitment (acceptability) and retention in the intervention 91/230 identified, 62 consented, and 60 actually completed MI in first visit No difference between consenters and decliners in demographics and clinical characteristics N of sessions attended associated with low SES (more session low SES) affective states (more depression and anxiety), lower QoL, worse illness perceptions 31
Primary outcomes Primary outcomes: Self-reported medication adherence adherence Visit 1, Baseline Visit 2 (6 months after BL) Follow-up (12 months after BL) 10.69 (4.80) Mean (SD) 9.74 (4.35) 10.90 (4.67) Median 10 12 11 Paired comparisons using Wilcoxon Signed-Rank non- parametric test Non-significant effect, d=0.22 Significant effect, d=0.26 32
Auxiliary outcomes: medications habit and beliefs and rating of importance and efficacy Habit and beliefs: No significant differences were found between at Visit 1 and Visit 2 (P s > .05). Importance and efficacy rulers : Significant differences in between Visit 1 and phone booster; non-significant differences between Visit 1 and Visit 2 . 33
Conclusions Conclusions 34
Main findings Main findings and comparison with lit Intervention is feasible: 2/3 agreed, ~1/2 of those identified completed; more retention among the worse-off psychologically Need for psycho-social support evident. Efficacy: Adherence increased at 6 months, then reverted at 12 months ( triangle effect ). Needs augmentation/additional boosters; blended approach recommended Small effect size, congruent with meta-analysis results. 35
Strengths Strengths Tailored, personalized Tailored, personalized intervention to the specific participant, employing in-person sessions with 2 health professionals and demonstrating a commitment to extensive patient extensive patient- -provider communication communication Utilized an intervention mapping approach. PAP theoretical model. Long follow-up uncovered a fade-off. provider 36
Limitations Limitations Small Small sample size No control group (due to small N) Upscaling Upscaling could require structuring the intervention; less personal but maybe more digital tools Communication outside clinic was restricted by HMO; policies changed since COVID. EMA recommended EMA recommended, capturing times of need and provides options for prompts, just-in-time response to a decrease in medication adherence; could be integrated into patient support programs of pharma companies. Need to tailor intervention to decliners intervention to decliners. Qualitative work needed on reasons and needs. Intervention addressed only patient and therapy-related factors and not healthcare system and condition-related. 37
Personal Note: Long Road Work started 10 years ago IRB, registration, Still producing publications Satisfying contribution Neter, E. & Miller, A. (2023). Using an intervention mapping approach to improve adherence to Disease-Modifying Treatment in Multiple Sclerosis. International Journal of Multiple Sclerosis Care, 25 (5). doi: 10.7224/1537-2073.2022-018. Neter, E., Glass-Marmor, L., Wolkowitz, A., & Miller, A., (2022). Medication habits among persons with multiple sclerosis. Multiple Sclerosis and Related Disorders, 68, 104224.doi.org/10.1016/j.msard.2022.104224 Neter, E., Glass-Marmor, L., Haiien, L., & Miller, A. (2021). Concordance between persons with Multiple Sclerosis and physician on medication effect and health status. Patient Preference and Adherence, 15, 939-943.doi: 10.21203/rs.3.rs-45699/v2 Neter, E., Glass-Marmor, L., Wolkowitz, A., Lavi, I., & Miller, A. (2021). Beliefs about medication as predictors to medication adherence in a prospective cohort study among patients with Multiple Sclerosis. BMC Neurology, 21, 136. doi:10.21203/rs.3.rs-45699/v1. Neter, E., Wolkowitz, A., Glass-Marmor, L., Lavi, I., Ratzabi, S., Lejbkowicz, I., & Miller, A. (2020). Multiple modality approach to assess adherence to medications across time in Multiple Sclerosis. Multiple Sclerosis and Related Disorders, 40, 101951. doi: 10.1016/j.msard.2020.101951. 38
neter@ruppin.ac.il Thanks to our participants Thank you for listening. 39
Come to EHPS conference in Come to EHPS conference in Cascais, Portugal, Cascais, Portugal, September September 2 2- -6 6, , 2024 2024 40
WHO model of Medication adherence WHO model of Medication adherence Adherence is multi-factorial Examples to dimensions/factors: 1 - age, education, marital status, having kids. 2 access to care, out-of-pocket, 3 lack of symptoms, severity of symptoms, addiction 4 method of administration (pills/injections/..), time spent on trt, number of times/day, 5 self care/management skills, efficacy, emotions, perceptions .. 41
