Effectiveness of a Self-care Intervention for Depression in Primary Care Patients With Chronic Physical Illnesses
Effectiveness of a Self-care Intervention for Depression in Primary Care Patients With Chronic Physical Illnesses
When patients present with both a chronic disease and depression, family physicians agree
 that treatment and follow-up is more complicated and that patients' health suffers as a
 result. Programs to help depressed patients learn skills to help manage their mood have been
 developed (depression self-care), using workbooks and audio-visual materials. The programs
 show promise, but little is known about how these self-care programs may work for patients
 with depression and chronic disease.

 Researchers are proposing a study to evaluate a depression self-care programme for patients
 age 40 and over who have at least mild depressive symptoms as well as a chronic physical
 illness and who are treated primarily by a family physician. All study participants (250
 patients selected from different family medicine clinics in Montreal) will receive a package
 of depression self-care materials which include the Antidepressant Skills Workbook, developed
 in Canada, available in French and English, and used in several provinces in depression
 self-management programs; a video on depression; a mood monitoring tool; an information
 booklet to give to family members; and information on additional resources (books, internet
 materials, and local community groups). The participants will be assigned to one of two
 groups randomly (like a coin toss): one group will receive the materials only, the other
 group will receive the materials as well as regular telephone support for up to 6 months by a
 trained coach who will answer any questions the participant may have on the materials they
 are working with.

 All participants who agree to be in the study will be interviewed three times: once at the
 beginning of the study, then at 3 months and finally at 6 months. Patients' depression scores
 will be evaluated to determine the effectiveness of the self-care programme with and without
 the support of the coach. Researchers will also look at the effect that self-care may have on
 use and costs of health services, and whether engaging in self-care has an impact on health
 behaviours (like exercise, taking medications correctly and smoking and alcohol consumption).

 All study data will be anonymous; any information that could potentially allow identification
 of a participant will be removed.
Contact principal investigator for references/citations.

 1. PRINCIPAL RESEARCH QUESTIONS AND HYPOTHESES We propose to conduct an RCT to measure the
 effectiveness of a telephone-based supported self-care intervention for depression in
 comparison to an unsupported self-care intervention among community-dwelling persons aged 40
 and over with depression (diagnoses and symptoms) and comorbid chronic physical illnesses in
 primary care settings.

 We propose to conduct a pragmatic trial that will be relevant to health policy. In keeping
 with this, we will endeavor to make the methods of recruitment and intervention delivery
 similar to those that would be used in "real-life" implementation.

 All outcomes will be assessed at the end of the intervention (6 months). Because the effects
 of the intervention on healthcare services utilization may not be seen within this time
 window, we will assess utilization and costs at both 6 and 12 months.

 Primary research question: What is the effectiveness of the supported versus unsupported
 intervention as evaluated by the severity of depressive symptoms at 6 month follow-up?

 Secondary research questions:

 1. What effects does the intervention have on the following (at 6 months unless otherwise
 specified): self-reported utilization of health-related services; utilization and costs
 of physician and hospital services at 12 months; general health status; depression
 diagnoses and treatments; severity of anxiety symptoms; activation and self-efficacy;
 health behaviors (exercise, social and leisure-time activities, smoking and alcohol
 consumption, medication adherence); self-care tool use; and patient satisfaction with
 the intervention?

 2. Are the effects of the intervention on the primary depression outcome mediated by the
 following: use of the self-care tools; activation; self-efficacy; or health behaviors?

 3. Does the effectiveness of the intervention vary by the following baseline variables:
 patient sociodemographics (age, sex, level of education, family income, language of
 intervention); physical health (physical function, multimorbidity, chronic pain); mental
 health (severity of depression, comorbid anxiety, alcohol abuse, mild cognitive
 impairment); level of activation; level of self-efficacy; type of primary care clinic;
 FP involvement in study; family involvement in chronic disease self-care; date of
 randomization, and time elapsed between screening and randomization.

 Descriptive research questions:

 1. What are patient perceptions of the support for self-care of their family member(s) or
 friend(s) who provide the most tangible and emotional support?

 2. What are family physician (FP) perceptions of the self-care intervention(s) and the
 information provided to them on the patients' depressive symptoms?

 1.1. HOW WILL THE RESULTS OF THIS TRIAL BE USED? This trial proposes an intervention designed
 to be applicable within Canadian healthcare, as modeled in Quebec urban areas. The study will
 use some aspects of the participatory research model and integrated knowledge translation,
 including input and feedback from national and local stakeholders in aging and mental health.
 An Advisory Committee has been formed, with members from various stakeholder groups: Canadian
 Coalition for Seniors' Mental Health, Action on Mental Illness Quebec. Input will be sought
 from these individuals and groups prior to, during, and after the trial, with the goal of
 optimizing use of the results in a collaboratively-developed strategic action plan for
 implementation of results for submission to stakeholders at national, provincial, and
 regional levels across Canada.

 2. TRIAL DESIGN The trial design adheres to the CONSORT criteria, the CONSORT extension for
 pragmatic trials, and guidelines for behavioral trials. The trial is a single blind,
 individually randomized, pragmatic trial of a telephone-based supported self-care
 intervention for depression compared with an unsupported self-care intervention.

 Patients will be recruited from a range of different Montreal-area primary care settings
 (including family medicine groups, CLSCs, solo and small group practices). In keeping with
 the pragmatic nature of this trial, screening/referral options will be flexible and may
 include: 1) waiting room or other screening methods; and 2) provider referral. [We will be
 conducting focus groups in September with FPs who participated in the pilot study to discuss
 other screening methods.] Eligible subjects will be invited to a face-to-face meeting with a
 research assistant at which the study will be presented and the patient will be invited to
 sign the consent form. The baseline interview will follow informed consent, and the patient
 will be randomized to one of the 2 treatment groups. Follow-up interviews will be conducted
 at 3 and 6 months post-randomization.

 2.2 PARTICIPANTS

 2.2.1 Recruitment of Clinics A purposive, convenience sample of Montreal area family medicine
 clinics within practical travel distance from the St. Mary's Research Centre will be created,
 aiming for representation from the following common types of practice: CLSC, family medicine
 group, other group, and solo practice. Clinic directors and / or individual doctors will be
 approached to determine their interest in participation.

 2.2.2 Patient Inclusion and Exclusion Criteria

 Described elsewhere in this record.

 2.2.3 Patient Recruitment Patients will be recruited in 4 steps: 1) referral of potentially
 eligible patients; 2) screening interview; 3) recruitment meeting; and 4) randomization.
 (Contact principal investigator for details).

 2.3 PLANNED TRIAL INTERVENTIONS

 Described elsewhere in this record.

 2.4 RANDOMIZATION METHOD We will randomize patients individually rather than in clusters
 (e.g, by FP). Based on our experience in the pilot study, we expect minimum contamination
 among the 2 intervention groups, and very little interaction between patients and FPs
 regarding the intervention. Patients will be randomized to the experimental and control
 interventions using randomization stratified by clinic/FP and method of recruitment
 (screening vs referral). Within each stratum, randomization sequence was created using random
 block sizes of 2 or 4 with an allocation ratio of 1:1. SAS software version 9.3 was used to
 generate and randomly assign patients to one of the two groups. Electronic or telephone-based
 randomization methods are not appropriate in the context of a face-to-face interview, often
 in the patient's home. Therefore, the planned randomization assignment will be provided in a
 sealed, opaque envelope to the RA who administers the baseline interview following the
 patient's written consent. The sealed envelope will be opened after completion of the
 interview, and the patient will be provided with the appropriate package of materials (either
 in person, or by sealed courier delivery). If the patient does not consent, or if the
 interview is never completed (patient does not present to the meeting, or is never available
 for a phone interview), the envelope will be used for the next patient within the same
 stratum.

 2.5 PREVENTION OF BIAS It will not be possible to blind subjects or their FPs to study group
 assignment. However, the patient assessments will be blinded as far as possible: follow-up
 interviewers will not be informed of the subject's study group, and will have no contact with
 either coaches or FPs. Interviewers will also specifically request that patients do not
 divulge information on the type of intervention they received.

 2.6 TREATMENT DURATION The supported intervention will be delivered for up to 6 months from
 randomization.

 2.7 FREQUENCY, DURATION AND METHOD OF FOLLOW-UP Participants will be followed up at 3 and 6
 months after enrolment using telephone interviews.

 2.8 PRIMARY AND SECONDARY OUTCOME MEASURES

 Described elsewhere in this record.

 2.9 PATIENT MEASURES We will collect patient data on the following 5 occasions: 1) at step 1
 identification of interested patients; 2) at step 2 telephone screening for eligibility; 3)
 at the baseline interview; and 4-5) at 3- and 6-month telephone follow-up interviews.
 (Contact the principal investigator for details on baseline, outcome and process of care
 measures).

 2.9.1 Adherence to the coaching intervention In the supported self-care arm, patient
 compliance with the intervention protocol will be examined using data from the coach logs and
 the 3 and 6-month summaries. Coaches will record all contacts attempted and completed,
 duration of completed contacts, topics covered, and patient progress with self-care
 intervention, the tools they recommended and problems that arose. At 3 and 6 months after
 randomization, coaches will summarize for each patient the specific tools recommended by the
 coach to date, and which tools the patient used.

 We will also measure coach adherence to the intervention protocol. Coach contacts will be
 recorded for qualitative analysis and for monitoring the fidelity of the intervention. The
 coach trainer will be responsible for monitoring the integrity of these interventions by
 rating of a 20% random sample of recorded sessions (2 sessions per patient), using a scale
 developed for the study. A random sample of 50 assessments will be selected, to include a
 total of five calls for each of the following types of call: 1)1st call, 2) 2nd call, 3)
 interim call, 4) penultimate, 5) last call.

 2.10 QUALITATIVE DATA COLLECTION AND SAMPLE SIZE During the 6 month follow-up interview,
 patients are asked open-ended questions about what they liked most about the self-care
 program and what could be improved. A sample of 40 patients' audio-recorded interviews will
 be selected to be transcribed and analyzed to help explain how process factors may have
 impacted the effectiveness of the intervention and will also help to guide future research
 and practice by informing the development of a framework for outlining processes that support
 positive self- care experiences. Using the principle of segmentation, two groups will
 comprise patients who were satisfied with the intervention (one group for each type of
 intervention) and two groups will comprise patients who were not satisfied with the
 intervention (one group for each intervention type).

 At the 6-month time point, participants will be invited to designate the family member or
 friend most involved with management of their chronic physical illness and/or mood. If the
 patient consents, we will collect this person's contact information. We will mail identified
 family members an invitation to participate in a structured interview, with 2 copies of the
 consent form, along with a pre-paid return envelope. One reminder mailing will be sent 3
 weeks after the first mailing. A research assistant will follow-up by telephone to schedule a
 1 hour telephone interview with family members who return the consent form. We estimate that
 ~30 patients will provide their family member's contact information and that ~10 family
 members will consent to participate. As we are currently preparing the next phases of this
 research program, these structured interviews will allow researchers to explore the ways in
 which family members and friends could be a source of support for people using depression
 self-care tools. Consent forms and interview guides will be approved by the ethics committee.

 2.11 SAMPLE SIZE FOR QUANTITATIVE DATA Our target sample size is 100 for each of the 2 arms.
 Assuming a 20% attrition rate over 6 months, we will recruit 125 patients into each arm, for
 a total sample size of 250. This sample size of n=100 in each group at 6 months, will give us
 sufficient power (>80%) to detect, at the 5% level of significance (2-sided test), an effect
 size of at least 0.4 for the primary outcome PHQ-9, as well as for other continuous scale
 outcomes. Cohen considers such an effect size as small to medium.

 For the binary secondary outcomes (e.g. major depression diagnoses at 6 months), in the
 "worst case scenario" (i.e. one of the two proportions is equal to 50%), a sample size of 100
 patients in each group will have 60% power to detect a difference of 15% between the two
 proportions at the 5% level of significance. The power will increase as the two proportions
 are assumed to be lower than 50%. Based on the pilot study, most of these proportions are
 likely to vary between 10% and 30%. For example in the pilot study, the proportion of major
 depression at 6 month was 23%, the power to detect the same difference of 15% will then be
 66%. The proportion of heavy use of alcohol at 6 month is 13%, the power to detect the same
 difference of 15% will then be 77%.

 The sample size calculations are conservative in that stratification (i.e. randomization
 within clinics and method of recruitment (screening or referral) and the longitudinal aspect
 of the design (repeated measurements at baseline, 3 and 6 months) are not taken into account.
 However, at the analysis stage both aspects will be taken into account; as a result, power to
 detect differences should be higher than computed above.

 2.12 PLANNED RECRUITMENT RATE AND LIKELY RATE OF LOSS TO FOLLOW-UP The sample of 250 will be
 recruited over a period of 8 months, an average of 7-8 patients per week. We estimate a
 maximum attrition rate of 20% for the primary outcome. In our pilot study, the attrition rate
 at 6 months was 55/63 (13%).

 2.13 PROPOSED QUANTITATIVE ANALYSES

 Handling of missing data on measures All the validated scores will be pro-rated, providing
 that the percentage of missing items does not exceed 25%. When more than 25% of the items are
 missing, the score will be treated as missing. The SF-12 score involves more complex scoring,
 a simple imputation algorithm will be applied in cases of missing data. When the percentage
 of missing values of a categorical variable does not exceed 1%, imputation by modal values
 will be performed. For a categorical variable for which the percentage of missing values
 exceed 1% , 'missing' will be defined as an additional level of the variable.

 Primary research question: What is the effectiveness of the supported versus unsupported
 intervention as evaluated in terms of the severity of depressive symptoms at 6 month
 follow-up? After the direct comparison of the two study groups, we will investigate possible
 clinically relevant baseline imbalances in prespecified important covariates. In the event of
 baseline imbalance, the salient patient characteristics will be included as covariates in the
 appropriate regression model. This is consistent with the recommendations in the CONSORT
 guidelines and in particular, see Altman.

 The primary outcome PHQ-9 (depression severity at 6 months) is a continuous variable measured
 at the patient level, and patients are clustered within clinics and FP. The comparison
 between treatment and control groups will be based on the linear mixed model; this will allow
 us to model the multi-level structure of the RCT by treating the clinic and the FP effects as
 random effects (random intercepts).

 A descriptive analysis of the characteristics of the drop-outs (at 3 and 6 months) will be
 performed to investigate the mechanism of missing values, in an attempt to assess the missing
 at random (MAR) hypothesis.

 Analysis of this primary outcome will be by intention-to-treat (ITT). However, a strict ITT
 analysis may be hard to achieve: for example, preliminary data suggest that a considerable
 proportion of patients drop out before the 6 month assessment (about 20 % in each group). Our
 primary method to address the missing data problem will be the Inverse Probability Weighting
 (IPW) approach. To implement IWP, we plan to use all available outcome information.

 Our choice of the IPW approach is based on several reasons. Of these the most important one
 in our situation is that IPW requires fewer assumptions. Indeed, IPW requires a model for the
 probability that an individual is a complete case; in contrast, MI requires a model for the
 distribution of the missing data given the observed data.

 Two sensitivity analyses will be conducted: 1) Analysis of available data only (completed
 information of the outcome variable at 6 month) 2) MI using available patient information;
 results across 10 imputed data sets will be combined. Note that MI will give unbiased results
 if the MAR hypothesis is correct.

 Both IPW and MI are based on a predictive model with study group and other patient
 characteristics as predictors. We will develop this model using the baseline patient
 variables.

 Note that in the results we will report the actual p-values of the tests and a confidence
 interval of 95% for the effect sizes.

 Secondary research question 1: What effects does the intervention have on the following
 outcomes (at 6 months unless otherwise specified): self-reported utilization of
 health-related services;utilization and costs of physician and hospital services at 12
 months; general health status; depression diagnoses and treatments; severity of anxiety
 symptoms; activation and self-efficacy; health behaviors (exercise, social and leisure-time
 activities, smoking and alcohol consumption, medication adherence); self-care tool use; and
 patient satisfaction with the intervention? We have selected 5 main secondary outcomes. For
 these analyses we will consider complete data only as the main approach for handling missing
 data. Baseline imbalance will be handled as for the primary outcome, adjusting for the same
 list of variables.

 For the overall costs outcomes, we will work with total costs over a period of 12 months. To
 compare treatment and control groups, we will use regression models that take account of the
 skewed and censored nature of cost data (generalized linear models, conditional density
 estimation, and hurdle models, among others). All the other main secondary outcome (all
 continuous) will be analyzed the same way as the primary outcome (linear mixed model).

 For the remaining secondary outcomes we will adopt an exploratory, flexible approach. For
 example, we will consider a Principal Component Analysis (PCA) of these outcomes in search of
 clinically interpretable dimensions, and define scores which can then be used as summary
 (secondary) outcomes.

 Secondary research question 2: Are the effects of the intervention on the primary depression
 outcome mediated by the following: use of the self-care tools; activation; self-efficacy; or
 health behaviors? Using approaches developed by Van der Weele and colleagues we will estimate
 the extent to which overall effects on the primary outcome are mediated through changes in
 the mediating variables of interest. These methods, based on potential outcomes
 (counterfactual) theory and inverse probability weighted marginal structural models, allow
 estimation of the mediating effects while preserving the structure of the randomization.
 Briefly, a marginal structural model is built for the outcome as a function of each mediator
 and randomization. The controlled direct effect of the randomized intervention, i.e., the
 effect of intervention holding the mediator(s) constant, is easily estimable from this model,
 while under further assumptions the so-called "natural" indirect effect, i.e., the effect
 mediated through individual mediators, can also be estimated.

 Secondary research question 3: Does the effectiveness of the intervention vary by the
 following baseline variables: patient sociodemographics (age, sex, level of education, family
 income, language of intervention); physical health (physical function, multimorbidity,
 chronic pain); mental health (severity of depression, comorbid anxiety, alcohol abuse, mild
 cognitive impairment); level of activation;level of self-efficacy;type of primary care
 clinic; FP involvement in study; family involvement in chronic disease self-care; date of
 randomization, and time elapsed between screening and randomization.

 In this analysis we will consider complete data only as the main approach for handling
 missing data. Also, baseline imbalance will be handled as for the primary outcome, adjusting
 for the same list of variables.

 For the pre-specified modifier variables, which we consider of primary importance, we will
 perform subgroup analyses. The remaining covariates will be introduced in the regressions and
 the corresponding interaction effects with treatment will be tested. For covariates with
 significant (p< 0.1) interactions we will conduct stratified analyses.

 2.14 PROPOSED FREQUENCY OF ANALYSES No interim analyses of outcomes will be conducted.
 Baseline characteristics of experimental and control groups (age, sex, PHQ-9 score, chronic
 diseases) will be monitored, in order to detect and rectify possible important imbalances
 occurring by chance.

 2.15 PLANNED SUBGROUP ANALYSES The role of 5 selected modifiers will be examined in sub-group
 analyses: age, level of education, depression diagnosis, cognitive impairment, and perceived
 family support with chronic disease self-care. [Despite the importance of sex as a modifier,
 we do not plan sub-group analysis by sex because of the small sample of men enrolled in the
 study.]

 • Age We hypothesize that the supported intervention will be equally effective as the
 unsupported intervention in the following age groups: 40-54, 55-64, 65+. To our knowledge,
 there is no evidence to date that age per se modifies the effectiveness of self-care
 interventions. Age was not associated with improvement in PHQ-9 scores in our pilot study.

 We hypothesize that the supported intervention will be more effective than the unsupported
 intervention among participants with the following patient characteristics:

 -  Depression diagnosis Prior research on differences in effectiveness of depression
 self-care intervention suggests that a diagnosis of major depression will be associated
 with greater effectiveness of the intervention. The metaanalysis by Gellatly found that
 RCTs with patients with pre-existing depression (vs those at-risk) was associated with
 greater effectiveness. Jerant studied an intervention to enhance patient self-efficacy
 for self-managing chronic illness, and found that individuals with more depressive
 symptoms were more likely to experience self-efficacy gains. We will analyze the
 following sub-groups: major depression, minor depression, neither.

 -  Higher level of education We hypothesize that participants with higher education will
 benefit more from the intervention. People with less education have higher rates of
 discontinuation of self-care interventions. A nurse-administered minimal psychological
 intervention for depressive symptoms among diabetics found that the intervention was
 effective only in higher-educated persons. We will analyze the following education
 sub-groups: university, high school, less than high school)

 -  Absence of cognitive impairment People with cognitive impairment may have greater
 difficulty in understanding the self-care materials. In our pilot study, greater
 cognitive impairment was associated with less improvement in the PHQ-9 outcome. We will
 examine participants with a BOMC score of 5-9 (versus less than 5).

 -  Greater perceived family support with chronic disease self-care. We hypothesize that
 participants who receive more frequent help from family or friends with chronic disease
 self-care will benefit more from the intervention. Studies of self-management for
 chronic physical illnesses have found a positive relationship between social support and
 self-care, especially for diabetes, and for dietary behavior. In our pilot study, we
 found that patients' use of the behavioral tools was positively associated with
 patients' report of support from family/friends for the depression intervention, and
 with family/friend reports of assistance with instrumental activities of daily living.
 We propose to examine 3 sub-groups defined by the mean frequency per week of assistance
 in 5 self-care activities (healthy eating, exercise, medications, symptom monitoring,
 medical care): 1) never, 2) rarely- some days, and 3) many days - almost every day.

 Additional potential modifiers will be analyzed using exploratory techniques, as described in
 section 2.15, secondary research question 3: sex, family income, language of intervention,
 physical function (PCS), multimorbidity, chronic pain, severity of depression symptoms (PHQ-9
 score), comorbid anxiety, alcohol abuse, level of activation; level of self-efficacy; type of
 primary care clinic; FP involvement in study; date of randomization, and time elapsed between
 screening and randomization.

 2.16 PROPOSED QUALITATIVE ANALYSIS Contact principal investigator for details.

 3 TRIAL MANAGEMENT Contact principal investigator for details.

 3.1 ETHICAL ISSUES In accordance with relevant guidelines in the Tri-Council Policy Statement
 and in the Plan d'action ministériel en éthique de la recherche et en intégrité scientifique,
 study protocols, consent procedures and forms will be submitted to institutional research
 ethics committees. Patient identifiers will be removed before entering into databases for
 analysis.

 Staff and trainees who have patient contact will be trained to identify potential risks to
 study participants, including suicidality, severe depression and cognitive impairment.

 Suicidality. Depressed patients may bring up suicidal thoughts during research interviews
 (including the screening interview) or during coach contacts. Staff (interviewers or coaches)
 are trained to follow-up in those cases and determine whether the patient has any intent or
 plan to act on these thoughts. If a patient expresses any intent to act on suicidal thoughts,
 staff will:

 1. Ask whether we may inform the FP of the subject's feelings. If the subject consents, the
 FP office will be contacted immediately.

 2. Ask whether the subject would like to speak with the study psychologist (see 3.1). If
 the subject consents, subject's contact information will be provided to the study
 psychologist who will follow-up within 24h.

 3. All subjects will be provided with the telephone numbers of the emergency psychiatry
 nurse at St. Mary's Hospital and will be provided with the number of Suicide Action
 Montreal's hotline. Subjects will be encouraged to use these numbers.

 Subjects with suicidal plans identified at the screening interview will be excluded from the
 study. Subjects with suicidal plans during follow-up will be withdrawn from the study.

 Severe depression. The following protocol will be followed for subjects who have severe
 depressive symptoms (PHQ-9 score of 20 or more) at enrollment into the study:

 1. subjects will be informed that they have severe depressive symptoms and will be
 encouraged to see their family doctor;

 2. if the subject consents, the FP will be informed and an appointment arranged; and

 3. the subject will be provided with the telephone number of the St. Mary's Hospital
 Emergency Psychiatry Nurse.

 Cognitive impairment. For subjects with cognitive impairment during the telephone screening
 interview, we will:

 Ask whether we may inform the FP of the subject's possible memory problems. If the subject
 consents, the FP office will be notified.
Inclusion Criteria:

 -  aged 40 or more;

 -  with one or more doctor-diagnosed chronic physical illnesses or chronic pain at least
 6 months duration;

 -  and with persistent depressive symptoms (≥ 1 month)

 Exclusion Criteria:

 -  PHQ-9 score of less than 5,

 -  resident in a nursing home,

 -  suicidal,

 -  receiving CBT from any health professional,

 -  unable to read in either English or French,

 -  more than mild cognitive impairment,

 -  any other impairment that would prevent them from participating in telephone
 interviews