Background Adherence is an active process wherein the patient acts in collaboration with the
medical and paramedical staff in order to improve his/her health. Adherence to medication
comprises of implementation and persistence and it is estimated to be around 50% in various
chronic illnesses. Lack of persistence is the greater impediment to adherence in most cases
(drops to approximately 60% over the course of a year). Non-adherence to prescribed treatment
increases the frustration of both the patient and provider and can increase health care
costs, including unnecessary hospitalizations and illness exacerbation.
A review of the World Health Organization (WHO) on adherence to therapy reveals a dynamic and
complex issue associated simultaneously with several factors: social and economic factors,
factors related to the health care team/system, characteristics of the disease,
characteristics of the disease therapies and patient-related factors. In this latter category
of patient-related issues this review identifies the following as major barriers: lack of
information and skills, low motivation and self-efficacy, and lack of support for behavioral
changes. Other patient related issues that influence adherence include patients' attributes:
affective attributes (depression and anxiety) and cognitive attributes (illness- relevant
cognition, perceptions of disease factors, and beliefs about treatment). The review
emphasizes that low adherence is not a given fact and because of its vast significance, the
WHO targeted it as "the best investment for tackling chronic conditions effectively" .
Phillips, Leventhal & Leventhal propose to add two processes that occur after behavior
initiation that are theorized to contribute to prediction of long term medication adherence:
'coherence' of patients' beliefs from experiences with treatment and habit development.
Multiple Sclerosis (MS) is the most common neurologic disease affecting young adults and can
lead to severe physical disability and handicap.
Research on adherence in MS indicates adherence rates similar to those of other chronic
illnesses, namely hovering around 50% two years after beginning of treatment. Patients who
fail to properly adhere to their Disease Modifying Therapies (DMTs) regimen may be at
increased risk for the development of new central nervous system lesions, exacerbation, and
poorer quality of life.
Plausible reasons for the low adherence rates in MS mentioned in the literature include
patients' attributes, condition attributes and therapy related factors:
Among patients' attributes, the research indicates 2 affective attributes that can be related
to low adherence in MS: high prevalence of depression and anxiety. Research on cognitive
attributes indicates an association between illness' perception, perceptions of medication
and adherence in general, but to our knowledge, there's no research directly addressing this
issue. To our knowledge, there's no research on habit strength and adherence, although habit
strength was found predictive of low adherence in asthma patients and in patients with
hypertension.
Among the condition-related factors that should be considered in MS adherence are the
relapsing-remitting nature of the disease (medicines sometimes prescribed when the patient
feels well). There is evidence that patients with few observable symptoms are typically less
likely to adhere to complex medication regimens. Hancock and co-researchers found that
patients with relatively stable disease were more likely to demonstrate poor medication
adherence and poor appointment adherence.
Among the therapy related factors, 32% of non-adherence can be explained by the injection
mode of delivery. Until recently the only available DMTs in MS included three preparations of
beta interferon and glatiramer acetate. These therapies are all injected on a regular basis
and associated with immediate undesirable results: painful site reactions, flu-like symptoms,
increased spasticity, depression, and fatigue in a significant percentage of patients. In
addition, the non-direct effect of the agents (unlike painkillers) might be one of the
explanations for poor adherence. Recently, the FDA approved new DMTs for MS that are taken
orally. Although it is plausible that adherence rates would improve with medications taken
orally as opposed to injected medicines, there is some evidence to the contrary: for
instance, Mohr and co-researchers found that soreness at injection site was related to
continuing therapy; and Cramer found that patients with diabetes tend to be more adherent to
injected therapy than to oral drugs. Thus, adherence factors may be different in injected and
oral therapy, and it is important to study adherence in these two modalities.
We propose adherence to medication as a mediating variable between adjustment to MS and
health outcomes. To our knowledge, there is no research addressing directly the issue of
psychological interventions to promote adherence in MS. Significance This study will examine
factors known in the literature as affecting adherence to therapy in MS or in other chronic
illnesses in order to create a personal profile of adherence. This profile will allow the
development of interventions tailored to the personal needs and barriers of patients
regarding adherence. Improved adherence is expected to ensure treatment efficacy and may
prevent irreversible tissue damage, resulting in prevention of accumulating functional
disability. This work may serve as a model for the study of adherence to therapy and the
development of interventions in other chronic diseases.
Design 400 patients treated with or planned to begin treatment with injected or oral therapy
approved by the Israeli Ministry of Health for the treatment of MS will be recruited in
"Carmel" MS Center.
The proposed study will consist of 4 phases:
1. Personal profile
- - In order to better understand therapy adherence in patients with MS,
a personal profile of patient's attributes, condition and history of therapy, which
takes into account the factors related to adherence mentioned above, will be gathered
through questionnaires.
This profile will be called MyMS_PASS (My Multiple Sclerosis
Perception Adherence Scoring System).
2. Implementation and persistence -This phase includes tracking for 9 to 12 months the
patients' personal profiles, habits and coherence between expectations and reality.
3. Intervention
- - According to the profiles assigned in phase 1 and the rates of adherence
to therapy assessed in phase 2, all patients with the lowest adherence rates to therapy
will be offered an intervention in the modality of Motivational Interviewing (MI) with a
small psycho-educational component.
The intervention will be tailored to the person's
factors found as barriers to adherence. All non-adherent patients will be enrolled in an
intervention, and their adherence
- - pre and post intervention - will be compared.
The
intervention will be applied by a health psychologist. The content of 5-10% of the
meetings will be recorded in order to afford fidelity analysis (i.e., that the
intervention delivered was as intended).
4. Evaluation of the intervention- Interventions will be evaluated by determining adherence
to therapy and other relevant variables at baseline and at the end of the study for all
participants in the study. Adherence to therapy before and after the intervention in the
study and the control groups will be compared.
Study visits for data collection: Visit 1: Baseline- evaluation of illness and medication
perception, adherence and habits.
Visit 2: About 6 months after beginning of follow-up- evaluation of illness and medication
perception, adherence, habits and experiences with psychological interventions Visit 3: About
9 to 12 months after beginning of follow-up- Evaluation of adherence to therapy and of the
factors related to adherence. By the end of this period intervention will be offered to
patients that exhibit low adherence rates.
Visit 4: About 12 months after initiation of the intervention. Evaluation of adherence,
habits, depression and anxiety and quality of life, for all participants in the study.
Proposed questionnaires:
1. Personal Information Questionnaire. 2. Brief Illness Perception Questionnaire (BIPQ)
3. Beliefs about Medicines Questionnaire (BMQ)
4. Multiple Sclerosis Treatment Experience Questionnaire (MS-TEQ)
5. The Self-Report Habit Index (SRHI)
6. Questions about psychological intervention. 7. Adult Dispositional Hope Scale (ADHS)
8. Hospital Anxiety and Depression Scale (HADS)
9. The World Health Organization Quality Of Life (WHOQOL-BREF)
10. Clinical questionnaire (EDSS) (for clinician)
11. Clinical follow-up questionnaire (EDSS) (for clinician)
12. Probabilistic Medication Adherence Scale (ProMAS)
Study Population MS patients visiting the MS center clinic at the Carmel Medical Center,
treated or planned to begin treatment with injected or oral DMT for MS.
. Patients Recruitment MS patients visiting the MS center clinic at the Carmel Medical Center
and responding to the inclusion criteria will be invited to participate in this study.
Participants will receive an explanation from Prof. Miller, or the attending neurologist
authorized by Prof Miller to do so, on the study aims and protocol. Patients who agree to
participate will sign an informed consent. Information regarding their personal and family
medical history, including data such as education and occupation, demographic and ethnicity
data will be collected via questionnaires. In addition, several questionnaires related to
adherence to treatment and patient's perception of treatment, disease and health will also be
filled by the participants during the study visits, as described in the table "Proposed
questionnaires" above. Medical staff will fill clinical questionnaires detailing patient
clinical status including adverse events at each study visit. Data will also be collected
from medical records, as necessary. Data collected through participants and physician filled
forms and from medical records will be stored coded in an Excel data base.
Ethical Issues Data collection and handling will be coded to assure privacy of participants
and will be handled by Prof. Ariel Miller and his authorized staff only. All the keys to the
codes will be locked. Participants' follow-up and visits to the clinic will continue as
usual. Patients' treatment will not be influenced by the study.
Intervention to promote adherence to therapy will be managed by a M.Sc. health therapist.
Ethical issues of the profession will be strictly kept.
Data Management Data collected through participants and physician filled forms and from
medical records will be stored coded in a data base. The database is password protected. Prof
Ariel Miller and his authorized staffs are responsible for its update and data verification.
Data Analysis Data analysis will be performed using the SPSS statistical package version 22.0
(SPSS Inc., Chicago, Illinois, USA). Comparisons of continuous characteristics of adherent
and non-adherent patients will be performed by Student's t-test or Mann-Whitney test,
according to data distribution. Categorical variables will compared using Chi square test or
Fisher's exact test for small sample.
To examine initiation and persistence of adherence to medication among patients, McNemar test
or Paired T test or Wilcoxon signed ranks test will be applied as appropriate.
Multivariable Logistic regression model will be used to examine the association between
illness perception and medication perception to adherence, controlling for background
variables such as depression, anxiety, time since diagnosis and medical condition. Odd Ratio
and 95 % confidence intervals will be calculated from the model.
The relationship between the variables in MyMS_PASS and the rates of adherence will be
assessed by multiple logistic regression.
Multivariable Logistic regression model will be used to assess the influence of interventions
on adherence, controlling for other parameters.
The association between the intervention and other continuous study parameters such as
motivation, goals, habit formation, and quality of life will be tested with T-test or
Mann-Whitney test.
Repeated measures tests will be employed to examine the effect of intervention on illness and
medication perception over time.
All p values will be two-sided, and statistical significance is defined as p<0.05.
