Eligible caregivers were 18 years and over, identified by the patient or self-identified as the primary caregiver, not employed by a healthcare organization, residing in Burgundy-Franche-Comté, able to understand and complete questionnaires. Caregivers belong to the immediate circle (family, friend or neighbor) of a patient aged 60 years or older with neuro-degenerative disease (idiopathic Parkinson’s disease or Alzheimer disease) diagnosed in the last months (last 12 months and then amended to the last 24 months), cancer (breast, prostate, or colorectal), age-related macular degeneration, and neuro-vascular disease (stroke). Non-inclusion criteria were caregivers of patients living in institution, principal caregivers under legal protection. All caregivers provided written informed consent. Detailed inclusion/exclusion criteria have been previously published.(12)
Caregivers were randomly assigned in a 1:1 ratio to the supportive interventional group or to the control group. Caregivers assigned in the supportive group received an intervention provided by a social worker and an information booklet. Caregivers randomized in the control group exclusively received the information booklet.
The intervention of a social worker was scheduled at 6, 12, 18 and 24 months (M6, M12, M18 and M24) after inclusion. The intervention consisted in a visit of one hour divided in two parts: firstly, qualify health difficulties encountered according to administration of the Linear Analogue Scale Assessment quality of life questionnaire.(13) Secondly, a standardized semi-directive interview aims to assess needs and detect early signs of burn-out. More details on social worker intervention were previously published.(12) Booklets provide concrete information on existing structures and support programs, and included concise information on local legislation, administrative procedures, daily life management and consequences related to the caregiving relationship.
Administration of questionnaires
All caregivers received questionnaires included HRQoL assessments using Medical Outcomes Survey Short Form-36 questionnaire (SF-36) for physical health component summary (SF-36-PCS), mental health component summary (SF-36-MCS), and detailed dimensions,(14-16) anxiety and depression with Hospital Anxiety Depression Scale (HADS),(17) and caregiver burden used Zarit Burden Interview (ZBI).(18-20) Scores were computed according to the respective recommendations.(14, 17, 21, 22) All questionnaires were self-administered quarterly except ZBI administrated six-monthly.
All scores for SF-36 subscales were computed on a 0 (worse HRQoL) to 100 (best HRQoL) point scale. The minimal important difference (MID) was defined as the smallest change in any scale within a patient (patient outcome self-identified as important) or at the group level. The MID was fixed at 5 points for SF‑36.(23) HADS anxiety and depression reported a raw score using a 0 (absence of trouble) to 21 (severe trouble) point range, with a MID fixed at 1.32 point for the HADS anxiety score, and at 1.4 point for the HADS depression score.(24) The ZBI reported a raw score using a 0 (no burden) to 88 (severe burden) point range, and the MID for ZBI was defined as half of the standard deviation observed at baseline, as usually performed for scores with no previously determined MID. To note, increased SF-36 scores translated an improved status, and increased HADS and ZBI translated a decreased status.
The ICE study faced caregiver recruitment difficulties and prematurely discontinued. The final sample size of the reduced ICE cohort did not allow to perform the statistical analyses initially planned.(12) Specifically, the lack of power prevent any comparisons between groups. Nevertheless, the initial primary and secondary endpoints were adapted to the current context and present results per randomized group: 1) SF-36 PCS and MCS summary scores mean change at M12 and M24 compared to baseline2) mean change at M12 and M24 for the subscales scores of the SF-36, HADS and ZBI compared to baseline; 3) the rates of caregivers with deteriorated, stabilized, and improved HRQoL, with SF-36 PCS and MCS, and SF-36 subscales, HADS and ZBI scores according to their respective MID at M12 and M24; and 4) longitudinal assessments of caregiver HRQoL, anxiety/depression and burden over the two years.
All analyses were performed using a modified intention-to-treat principle, i.e. including all caregivers allocated to randomization, with completed SF-36 questionnaire at baseline. The analyses included all data available at each considered timepoint. Only descriptive analysis per group were conducted.
Socio-demographic and clinical characteristics were described in the global population and in each randomization group. Categorical variables were expressed using number and frequency (n, %) and continuous variables with median (min-max). Mean (standard deviation)/median (min-max) scores were described at each timepoint in both groups. Mean changes in SF-36, HADS, and ZBI scores from baseline to M12 and M24, are presented per group with paired t-test fixed at 5% for statistical significance.
At the aggregate level, we reported in each group the rate of caregivers with SF-36-PCS, SF-36-MCS, HADS, and ZBI score changes from baseline to M12 and from baseline to M24, categorized as stable, deteriorated, or improved according to their respective MID.
Mixed models for repeated measures were used for longitudinal analysis of HRQoL including all timepoints until M24 and included the following variables: randomization group, time, allocation-by-time interaction, adjusted on baseline score, and baseline score-by-time interaction. Random effects on intercept and time were used in order to reflect individual variations at baseline and over time. Adjusted mean changes at M12 and M24 were reported with 95% confidence interval (CI) for SF‑36-PCS and -MCS scores, HADS anxiety and depression, and burden, per group. Statistical and MID clinical significances were indicated.
Analyses were performed using SAS version 9.4 software (SAS Institute Inc., Cary, NC, USA).