Primary outcome
The primary end point for the trial was patient-reported depression severity, as measured by the PHQ-933
at 4 months’follow-up. Each item is scored from 0 to 3; thus, PHQ-9 scores can range from 0 to 27, with higher scores indicating more severe depression. Total scores from 0 (non-depressed) to 27 (severely depressed) were calculated based on the nine PHQ-9 items. These data were collected via self-report on the follow-up questionnaires. Any participants who did not return a completed questionnaire were sent a reminder, and those participants who did not respond were telephoned by one of the study team’s researchers to ask them to complete the PHQ-9 over the telephone. Missing items were replaced with the mean of the remaining items if one or two items were missing.
The PHQ-9 data were collected at baseline and randomisation (at the diagnostic interview), as well as at 4, 12 and 18 months’follow-up. Scores at baseline and randomisation are reported inChapter 5,Baseline characteristics. When analyses were adjusted for initial PHQ-9 score, the score at randomisation was used. The primary end point for the CASPER plus trial was at 4 months’follow-up. At that point, treatment differences in the magnitude of a standard effect size of 0.35 were sought, which is of moderate size for psychological interventions and in line with collaborative care effects observed in other studies. Cohen50
classifies a standard effect size of 0.3 as a small to medium effect size, and this is in line with NICE guidelines for depression, which adopts a similar grading of clinical significance. Four months was selected
as the primary end point, because it would occur soon after the end of the planned treatment but allow some additional time in the event that it was not possible to see participants on a weekly basis for practical reasons (e.g. holidays).
Secondary outcomes
The secondary outcome measures used were:
l depression severity and symptomatology at 12 and 18 months (PHQ-9)
l binary depression severity at 4, 12 and 18 months (PHQ-9), using scores of≥10 to designate moderate depression caseness
l quality of life at 4, 12 and 18 months (SF-12 and EQ-5D-3L) l psychological anxiety at 4, 12 and 18 months (GAD-7) l mental health medication at 4, 12 and 18 months
l physical health problems at baseline, 4, 12 and 18 months (PHQ-15) l psychological resilience at baseline, 4, 12 and 18 months (CD-RISC2) l mortality at 4, 12 and 18 months.
Short Form questionnaire-12 items
The SF-1234is a generic health status measure and a short form of the Short Form questionnaire-36 items
health survey. It consists of 12 questions measuring eight domains (physical, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) rated over the past month. Questions have three or five response categories, and responses are summarised into a physical component summary (PCS) score and mental component summary (MCS) score. The PCS and MCS scores range from 0 (the lowest level of health) to 100 (the highest level of health) and were designed to have a mean score of 50 in a representative sample of the US population. Therefore, scores>50 represent above average health status, and vice versa. The SF-6D was estimated from responses to the SF-12 questionnaire and provided health-state utilities to inform cost–utility analysis.
EuroQol-5 Dimensions, 3 levels
The EQ-5D-3L35is a standardised measure of current health status developed by the EuroQol Group
for clinical and economic appraisal. The EQ-5D-3L consists of five questions each assessing a different quality-of-life dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension is rated on three levels: no problems (score=1), some problems (score=2) and extreme problems (score=3). A weighted summary index can be derived to give a score between 1 (perfect health) and 0 (death). For the purpose of the clinical effectiveness analysis, only scores of the individual dimensions were utilised. Health-state utilities (along with SF-6D) were estimated to potentially inform the cost–utility analysis; however, the SF-6D was ultimately found to be more sensitive to change in this cohort.
Generalised Anxiety Disorder-7 items scale
The GAD-736is a brief measure of symptoms of anxiety based on diagnostic criteria described inDiagnostic
and Statistical Manual of Mental Disorders-Fourth Edition.43It consists of seven questions and is calculated
by assigning scores of 0, 1, 2 and 3 to the response categories of‘not at all’,‘several days’,‘more than half the days’and‘nearly every day,’respectively. GAD-7 total score for the seven items ranges from 0 to 21. Scores of 5, 10 and 15 represent cut-off points for mild, moderate and severe anxiety, respectively.
Patient Health Questionnaire-15 items
The PHQ-1537is a 15-item physical health problems questionnaire. Each health issue is rated as 0 (not
bothered), 1 (bothered a little) or 2 (bothered a lot). Items are added to form a scale from 0 to 30, higher scores indicating worse symptom severity. Scores of 5, 10 and 15 have been used as cut-off points for low, medium and high symptom severity. Item 4 of the PHQ-15 (menstrual problems) was deemed not relevant for the older CASPER patient population and omitted from all questionnaires. Therefore, the total possible PHQ-15 score was 28.
Connor–Davidson Resilience Scale two-items
The CD-RISC238is a two-item short form of the full Connor–Davidson Resilience Scale-25 items. It is a
psychological resilience measure with specific items for bounce-back from adversity and adaptability to change. Agreement with the two items is scored from 0 to 4, resulting in a total score of 0 to 8, where a higher score indicates greater resilience.
Mental health medication
Medication data were captured by self-report on the follow-up questionnaires. Participants indicated prescribed medication by selecting from a list of 10 antidepressants, as well as listing any other medications they were prescribed.
Mortality data
A data linkage service was established with the NHS Digital to provide regular updates from the Office for National Statistics (ONS) mortality data on any trial participants who had died while in the study. Members of the research team recorded any identified deaths, date and cause of death on the study management database.