A Web- and Mobile-Based Intervention for Comorbid, Recurrent Depression in Patients With Chronic Back Pain on Sick Leave (Get.Back): Pilot Randomized Controlled Trial on Feasibility, User Satisfaction, and Effectiveness

Background Chronic back pain (CBP) is linked to a higher prevalence and higher occurrence of major depressive disorder (MDD) and can lead to reduced quality of life. Unfortunately, individuals with both CBP and recurrent MDD are underidentified. Utilizing health care insurance data may provide a possibility to better identify this complex population. In addition, internet- and mobile-based interventions might enhance the availability of existing treatments and provide help to those highly burdened individuals. Objective This pilot randomized controlled trial investigated the feasibility of recruitment via the health records of a German health insurance company. The study also examined user satisfaction and effectiveness of a 9-week cognitive behavioral therapy and Web- and mobile-based guided self-help intervention Get.Back in CBP patients with recurrent MDD on sick leave compared with a waitlist control condition. Methods Health records from a German health insurance company were used to identify and recruit participants (N=76) via invitation letters. Study outcomes were measured using Web-based self-report assessments at baseline, posttreatment (9 weeks), and a 6-month follow-up. The primary outcome was depressive symptom severity (Center for Epidemiological Studies–Depression); secondary outcomes included anxiety (Hamilton Anxiety and Depression Scale), quality of life (Assessment of Quality of Life), pain-related variables (Oswestry Disability Index, Pain Self-Efficacy Questionnaire, and pain intensity), and negative effects (Inventory for the Assessment of Negative Effects of Psychotherapy). Results The total enrollment rate with the recruitment strategy used was 1.26% (76/6000). Participants completed 4.8 modules (SD 2.6, range 0-7) of Get.Back. The overall user satisfaction was favorable (mean Client Satisfaction Questionnaire score=24.5, SD 5.2). Covariance analyses showed a small but statistically significant reduction in depressive symptom severity in the intervention group (n=40) at posttreatment compared with the waitlist control group (n=36; F1,76=3.62, P=.03; d=0.28, 95% CI −0.17 to 0.74). Similar findings were noted for the reduction of anxiety symptoms (F1,76=10.45; P=.001; d=0.14, 95% CI −0.31 to 0.60) at posttreatment. Other secondary outcomes were nonsignificant (.06≤P≤.44). At the 6-month follow-up, the difference between the groups with regard to reduction in depressive symptom severity was no longer statistically significant (F1,76=1.50, P=.11; d=0.10, 95% CI −0.34 to 0.46). The between-group difference in anxiety at posttreatment was maintained to follow-up (F1,76=2.94, P=.04; d=0.38, 95% CI −0.07 to 0.83). There were no statistically significant differences across groups regarding other secondary outcomes at the 6-month follow-up (.08≤P≤.42). Conclusions These results suggest that participants with comorbid depression and CBP on sick leave may benefit from internet- and mobile-based interventions, as exemplified with the positive user satisfaction ratings. The recruitment strategy via health insurance letter invitations appeared feasible, but more research is needed to understand how response rates in untreated individuals with CBP and comorbid depression can be increased. Trial Registration German Clinical Trials Register DRKS00010820; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00010820.

METHODS 3a) Description of trial design (such as parallel, factorial) including allocation ratio 3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons Does your paper address CONSORT subitem 2b? * "Thus, one aim of this pilot RCT was to investigate the feasibility of this recruitment strategy as well as the feasibility, user satisfaction and effectiveness of a guided IMI for CBP patients with depression on sick leave." "We expected the IMI to be more effective for reducing depressive symptom severity, pain-associated measures and for increasing Does your paper address CONSORT subitem 3a? * "The intervention was evaluated in a two-armed randomized controlled trial." "Participants eligible for the study were randomly allocated to one of two groups (intervention group or waitlist control group). An automated, web-based randomization program [28] was used, which features permuted block randomization. Variable, randomly arranged 4a) Eligibility criteria for participants Does your paper address CONSORT subitem 3b? * "This study was initially planned with a target sample of N=250. However, the trial did not reach the targeted sample of participants (N=76) due to changes in personnel in the insurance company responsible for sending invitation letters. Thus, the planned amount of invitation letters to be sent (12,000) were not delivered. The study was initially powered to detect medium effect sizes (d=0.40; N=200, power of 95%) and accounted for 25% dropout (N=250). Post-hoc analysis with N=76 revealed that we were able to detect effect sizes 3b-i) Bug fixes, Downtimes, Content Changes Does your paper address subitem 3b-i? Does your paper address CONSORT subitem 4a? * "In order to participate in the study, the following criteria must have been met: (a) recurrent diagnosis of MDD and chronic back pain (M54.x according to  in the past 16 months, (b) sick leave for more than a week but less than six months, (c) no lifetime diagnosis of psychosis, (d) no nursing care level 2 or higher […]and (d) no acute/recent cancer diagnosis in past 16 months. In addition, participants were eligible for the study if they: (a) were at least 18 years old, (b) had at least moderate depressive symptoms (Center for Epidemiological Studies Depression Scale; CES-D≥23 [23,24]), (c) sufficient German language proficiency, (d) had access to a computer with internet, an email address and a mobile phone and (e) internet/computer literacy. 4a-i) Computer / Internet literacy Does your paper address subitem 4a-i? 4a-ii) Open vs. closed, web-based vs. face-to-face assessments: Does your paper address subitem 4a-ii? * "Recruitment was carried out […]from October 2016 until the end of December 2017 […]" "Participants interested in the study contacted the research team and were asked to fill out a brief online screening to ensure inclusion criteria were fulfilled. Eligible individuals were given the required informed consent for participation and after returning it, an account for each participant was created. The account's user name was the by the participant provided email address. The account was password protected (password was chosen by participants in order to prevent misuse of their data). " "All study outcomes […]were measured using self-report assessments at baseline (t1), post-treatment (t2) and a 6-month follow-up (t3). A secure online-based system (AES, 256-bit encrypted) was used. " 4b) Settings and locations where the data were collected 4a-iii) Information giving during recruitment Does your paper address subitem 4a-iii?
Does your paper address CONSORT subitem 4b? * "Recruitment was carried out by the study team and supported by the German health insurance company (BARMER) from October 2016 until the end of December 2017 by sending invitation letters to policy holders (N=6,000)." "Participants interested in the study contacted the research team and were asked to fill out a brief online screening to ensure inclusion criteria were fulfilled. Eligible individuals were given the required informed consent for participation and after returning it, an account for each participant was created. The account's user name was the by the participant provided email address. The account was password protected (password was chosen by participants in order to prevent 5) The interventions for each group with sufficient details to allow replication, including how and when they were actually administered 4b-i) Report if outcomes were (self-)assessed through online questionnaires Does your paper address subitem 4b-i? * 5-viii) Mode of delivery, features/functionalities/components of the intervention and comparator, and the theoretical framework Does your paper address subitem 5-viii? * "[…] The online intervention is based on cognitive behavioral therapy (CBT) and consists of seven weekly modules lasting 45-60 minutes each. Modules include information regarding: psychoeducation, behavioral activation, problem solving, cognitive restructuring, return to work, self-esteem and relapse prevention (for a detailed description see Lin et al., 2017).
[…] The emphasis is particularly focused on homework assignments, which ideally leads to the application of the learned skills into daily routines. Interactive elements (e.g., E-Mails, text messages), reminders and exercises were used to enhance adherence to the intervention (for detailed information about the intervention see multimedia appendix 1)." " [...]In case of non-completion of the modules, eCoaches sent reminders to participants."

5-ix) Describe use parameters
Does your paper address subitem 5-ix?

5-x) Clarify the level of human involvement
Does your paper address subitem 5-x? 5-xi) Report any prompts/reminders used Does your paper address subitem 5-xi? * "If any further questions arose, participants and eCoaches were able to contact each other at any time via the platform. In case of noncompletion of the modules, eCoaches sent reminders to participants." "[…] Content included: (a) reminders to complete weekly assignments, (b) repetition of the content and (c) motivation enhancement components. In total, each participant received 42 text messages." " Interactive elements (e.g., E-Mails, text messages), reminders and exercises were used to enhance adherence to the intervention (for detailed information about the intervention see multimedia appendix 1)." For further information see manuscript, heading "INTERVENTION GROUP, GUIDANCE and TEXT-MESSAGE COACH" 6a) Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed 5-xii) Describe any co-interventions (incl. training/support) Does your paper address subitem 5-xii? * "The program is conceptualized as a stand-alone intervention in order to provide help to this difficult-to-reach population and complement conventional health care for depressed CBP." "All participants had unrestricted access to treatment-as-usual (TAU; e.g., visiting a general practitioner)." "All study outcomes […] were measured using web-based self-report assessments at baseline (t1), post-treatment (t2) and a 6-month follow-up (t3)." "Primary outcome: Depressive symptom severity at post-treatment. Depressive symptom severity was measured with the CES-D [23,24], a widely used instrument in IMI depression trials [14,36].
[…] Items include the most common symptoms related to depression, such as low mood, loss of appetite, concentration difficulties, and hopelessness. CES-D scores of 16 or greater indicate clinically relevant levels of depression severity. The CES-D has been shown to have excellent reliability (i.e., internal consistency of Cronbach's α = .89, [37]). In the present study, Cronbach's alpha was .82." For further information see manuscript, heading "PROCEDURE, and 6a-i) Online questionnaires: describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed Does your paper address subitem 6a-i? 6b) Any changes to trial outcomes after the trial commenced, with reasons 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored Does your paper address subitem 6a-ii? 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained Does your paper address subitem 6a-iii? 7a) How sample size was determined NPT: When applicable, details of whether and how the clustering by care provides or centers was addressed Does your paper address CONSORT subitem 6b? * "This study was initially planned with a target sample of N=250. However, the trial did not reach the targeted sample of participants (N=76) due to changes in personnel in the insurance company responsible for sending invitation letters. Thus, the planned amount of invitation letters to be sent (12,000) were not delivered. The study was initially powered to detect medium effect sizes (d=0.40; N=200, power of 95%) and accounted for 25% dropout (N=250). Post-hoc analysis with N=76 revealed that we were able to detect effect sizes 7a-i) Describe whether and how expected attrition was taken into account when calculating the sample size Does your paper address subitem 7a-i? "The study was initially powered to detect medium effect sizes (d=0.40; N=200, power of 95%) and accounted for 25% dropout (N=250). Posthoc analysis with N=76 revealed that we were able to detect effect sizes of d=0.65 with a power of 80%. " 7b) When applicable, explanation of any interim analyses and stopping guidelines 8a) Method used to generate the random allocation sequence NPT: When applicable, how care providers were allocated to each trial group Does your paper address CONSORT subitem 7b? * "To further assess serious adverse events (SAE), participants were asked at the beginning of each module about adverse events and were also encouraged to report any such events to their eCoach who monitored the SAEs and initiated further actions if needed." The trial would have been stopped, in case of serious adverse events.
No interim analyses were conducted. Does your paper address CONSORT subitem 8a? * "Participants eligible for the study were randomly allocated to one of two groups (intervention group or waitlist control group) based on an a priori defined list after completing the baseline assessment. An automated, web-based randomization program [28] was used, which features permuted block randomization. Variable, randomly arranged block sizes of 4, 6, 8 and an allocation ratio of 1:1 were adopted. An independent research team member not otherwise involved in the study conducted the randomization. Participants were not blinded to 8b) Type of randomisation; details of any restriction (such as blocking and block size) 9) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned 10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions Does your paper address CONSORT subitem 8b? * "Participants eligible for the study were randomly allocated to one of two groups (intervention group or waitlist control group) based on an a priori defined list after completing the baseline assessment. An automated, web-based randomization program [28] was used, which features permuted block randomization. Variable, randomly arranged block sizes of 4, 6, 8 and an allocation ratio of 1:1 were adopted." Does your paper address CONSORT subitem 9? * "Participants eligible for the study were randomly allocated to one of two groups (intervention group or waitlist control group) based on an a priori defined list after completing the baseline assessment. An automated, web-based randomization program [28] was used, which features permuted block randomization. Variable, randomly arranged block sizes of 4, 6, 8 and an allocation ratio of 1:1 were adopted." 11a) If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how NPT: Whether or not administering co-interventions were blinded to group assignment Does your paper address CONSORT subitem 10? * "An independent research team member not otherwise involved in the study conducted the randomization." The random allocation sequence was generated by the corresponding author; using an automated, web-based randomization program.
11a-i) Specify who was blinded, and who wasn't Does your paper address subitem 11a-i? * "Participants were not blinded to treatment condition." The research team could not be blinded, because of the necessary administrative needs for each participant.

11b) If relevant, description of the similarity of interventions
(this item is usually not relevant for ehealth trials as it refers to similarity of a placebo or sham intervention to a active medication/intervention) 12a) Statistical methods used to compare groups for primary and secondary outcomes NPT: When applicable, details of whether and how the clustering by care providers or centers was addressed 11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator" Does your paper address subitem 11a-ii?
Does your paper address CONSORT subitem 11b? * This is not applicable for the study.
Does your paper address CONSORT subitem 12a? * "Descriptive statistics for feasibility of recruitment, intervention usage, client satisfaction and relationship with the eCoach were reported. Analyses of covariance (ANCOVA) adjusted for sex, age and baseline symptom severity were performed to analyze primary and secondary outcomes between groups at post-treatment and 6-month follow-up. [...] Results are reported as mean within-and between-group differences and as Cohen's d effect sizes (and their 95% CIs, according to Hedges and Olkin [67] controlling for baseline scores (i.e., calculating change scores divided by the pooled standard deviation of change scores).
[…] Statistical significance in all analyses was set at α<0.05 and was 12a-i) Imputation techniques to deal with attrition / missing values Does your paper address subitem 12a-i? * "Missing data were imputed using a Markov chain Monte Carlo [66] multivariate imputation algorithm with 50 estimations per missing value in accordance with the intention-to-treat (ITT) principle." 12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses X26) REB/IRB Approval and Ethical Considerations [recommended as subheading under "Methods"] (not a CONSORT item) Does your paper address CONSORT subitem 12b? * "In addition, we performed per-protocol analyses to assess differences in the primary outcome between intervention completers and noncompleters. Participants were classified as intervention completers if they adhered to at least 80% of the intervention (5 out of 7 modules)." There were no more additional analyses conducted within this trial.

X26-i) Comment on ethics committee approval
Does your paper address subitem X26-i? "Study procedures were approved by the ethical board of the Friedrich-Alexander-University Erlangen-Nürnberg (323_15B) and the trial was registered in the German registry of clinical trials (DRKS00010820)." RESULTS x26-ii) Outline informed consent procedures Does your paper address subitem X26-ii?

X26-iii) Safety and security procedures
Does your paper address subitem X26-iii? "The account's user name was the by the participant provided email address. The account was password protected (password was chosen by participants in order to prevent misuse of their data)." "A secure online-based system (AES, 256-bit encrypted) was used." 13a) For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome Does your paper address CONSORT subitem 13b? (NOTE: Preferably, this is shown in a CONSORT flow diagram) * "Study procedures are documented in Figure 1." "Participants completed on average 4.8 (SD=2.6) modules of the intervention. In total, 24 (60.0%) participants in the IG were identified as completers. Of those 22 (55.0%) adhered to all seven modules. Of the 16 (40.0%) participants who did not complete at least five modules, one (2.5%) participant never started the intervention. Completers and noncompleter did not differ in their baseline characteristics." Does your paper address CONSORT subitem 14a? * "Recruitment was carried out by the study team and supported by the German health insurance company (BARMER) from October 2016 until the end of December 2017 by sending invitation letters to policy holders (N=6,000)." "All study outcomes except for the structured clinical interview for DSM-IV (SCID, [21]) were measured using web-based self-report 14b) Why the trial ended or was stopped (early) 14a-i) Indicate if critical "secular events" fell into the study period Does your paper address subitem 14a-i? Does your paper address CONSORT subitem 14b? * "This study was initially planned with a target sample of N=250. However, the trial did not reach the targeted sample of participants (N=76) due to changes in personnel in the insurance company responsible for sending invitation letters. Thus, the planned amount of invitation letters to be sent (12,000) were not delivered. The study was initially powered to detect medium effect sizes (d=0.40; N=200, power of 95%) and accounted for 25% dropout (N=250). Post-hoc analysis with N=76 revealed that we were able to detect effect sizes 15) A table showing baseline demographic and clinical characteristics for each group NPT: When applicable, a description of care providers (case volume, qualification, expertise, etc.) and centers (volume) in each group Does your paper address CONSORT subitem 15? * "In total, 76 participants were included in the study. For detailed information on characteristics, see Table 2." Demographic and clinical characteristics are reported for each group and the total sample in Table 2. 15-i) Report demographics associated with digital divide issues Does your paper address subitem 15-i? * "In total, 76 participants were included in the study. For detailed information on characteristics, see Table 2." Demographic and clinical characteristics are reported for each group and the total sample in Table 2. 16) For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups 16-i) Report multiple "denominators" and provide definitions Does your paper address subitem 16-i? * "The mean scores for outcomes are reported in Table 3. Table 4 displays results for all outcome measures." "Results revealed statistically significant reductions in the primary outcome from baseline to post-treatment in both the IG (reduction of 6.84 points on the CES-D [t40=5.82, P<.001, d=0.84, 95%CI:0.39-1.30]) and the WLC (reduction of 4.64 points on CES-D [t36=3.86, P<.001, d=0.64, 95%CI:0.17-1.12]). There was a statistically significant difference between the intervention and waitlist control group at posttreatment, resulting in a small between-group effect size favoring the intervention condition (F1;76=3.62, P=.03, d=0.28, 95%CI:-0.17-0.74).
There were no significant differences in the primary outcome between intervention completers and non-completers (F1;29)=0.01; P=.48)." For all analyses, denominators are reported. 17a) For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) 16-ii) Primary analysis should be intent-to-treat Does your paper address subitem 16-ii? "Missing data were imputed using a Markov chain Monte Carlo [66] multivariate imputation algorithm with 50 estimations per missing value in accordance with the intention-to-treat (ITT) principle." Does your paper address CONSORT subitem 17a? * "The mean scores for outcomes are reported in Table 3. Table 4 displays results for all outcome measures." Table 4 reports results and estimated effect sizes as well as confidence intervals of the primary and secondary outcomes. 17b) For binary outcomes, presentation of both absolute and relative effect sizes is recommended 18) Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory 17a-i) Presentation of process outcomes such as metrics of use and intensity of use Does your paper address subitem 17a-i? Does your paper address CONSORT subitem 17b? * This is not applicable for the study.