اثربخشی و هزینه کم رفتاردرمانی شناختی جداگانه طراحی شده با ارائه اینترنتی برای اختلالات اضطرابی در یک جمعیت تحت مراقبت های اولیه: کارآزمایی تصادفی کنترل شده

A significant proportion of the general population suffers from anxiety disorders, often with comorbid psychiatric conditions. Internet-delivered cognitive behavior therapy (ICBT) has been found to be a potent treatment for patients with specific psychiatric conditions. The aim of this trial was to investigate the effectiveness and cost-effectiveness of ICBT when tailoring the treatment to address comorbidities and preferences for primary-care patients with a principal anxiety disorder. One hundred participants were recruited through their primary-care contact and randomized to either treatment or an active control group. The treatment consisted of 7–10 weekly individually assigned modules guided by online therapists. At post-treatment, 46% of the treatment group had achieved clinically significant improvement on the primary outcome measure (CORE-OM) and between-group effect sizes ranged from d = 0.20 to 0.86, with a mean effect of d = 0.59. At one-year follow-up, within-group effect sizes varied between d = 0.53 to 1.00. Cost analysis showed significant reduction of total costs for the ICBT group, the results were maintained at one-year follow-up and the incremental cost-effectiveness ratio favored ICBT compared to control group. Individually tailored ICBT is an effective and cost-effective treatment for primary-care patients with anxiety disorders with or without comorbidities.

3. Results Adherence and attrition Adherence was measured by using the percentage of completed prescribed modules for the treatment group. Completion was defined as when the participant had sent in his or her homework assignment to the therapist for the prescribed module. All prescribed modules were completed by 32 per cent (16/50) of the treatment group. One participant (2%) did not complete any of the prescribed modules, while the mean completion rate was 53.5 percent of the prescribed modules. In the treatment group three persons dropped out, and two were excluded (for details, see Fig. 1), leaving 45 participants remaining in the treatment group at the end of the ten-week treatment period. In the control group, eight persons withdrew their application before starting the treatment. During the treatment of the control group, three participants dropped out, and two were excluded. Treatment effects Pre to post changes Effect sizes varied from d = 0.20 to 0.86 with a mean effect size of d = 0.59. In terms of treatment response, 46% (23/50) of the participants in the treatment group showed a clinically significant improvement on the CORE-OM, compared to 12% (6/50) in the control condition. Detailed data on the pre to post results are presented in Table 2. Table 2. Estimated means, standard error (SE), on all outcome measures at pre-treatment and post-treatment, effects, and between-group Cohen’s effect sizes (d) at post-treatment. Measure Time Treatment (n = 50) Control (n = 50) Effects F (1,89–97) a Between-group d CORE-OM Pre 18.44(0.63) 17.65(0.63) T: 95.51*** Post 10.97(0.75) 17.65(0.63) G: 5.097* 0.86 I: 28.82*** BAI Pre 21.18(1.37) 21.32(1.37) T: 68.334*** Post 11.81(1.10) 16.30(1.10) G: 2,305ns 0.58 I: 6.23* MADRS-S Pre 19.62(0.96) 17.84(0.96) T: 59.734*** Post 10.84(1.04) 15.94(1.04) G: 1.825ns 0.70 I: 24.77*** QOLI Pre 0.446(0.23) 0.865(0.23) T: 12.424*** Post 1.320(0.21) 1.033(0.21) G: 0.064ns 0.20 I:5.70* Abbreviations: CORE-OM Outcomes in Routine Evaluation – Outcome Measure; BAI, Beck Anxiety Inventory; MADRS-S, Montgomery Åsberg Depression Rating Scale-Self rated; QOLI, Quality of Life Inventory; T, Time; G, Group; I, Interaction time*group. ns non significant * = p < .05 ** = p < .01; *** = p < .001. a denominator degrees of freedom varied between 89.336 and 96.972. Table options When taking a comorbid mood disorder into consideration, no interaction effects of time and group and mood disorder were found on either the primary measure (F (1,90.026) = 1.666, p = .200) or on secondary measures (BAI; F (1,93.632) = 0.266, p = .608; MADRS-S; F (1,89.482) = 0.280, p = .598; QOLI; F(1,89.318) = 0.832, p = .364). Taken together, the results indicate that participants in the treatment group reported an improvement on all outcomes and the mean between-group effect was moderate. Comorbid depression did not moderate the outcome. Pre to follow-up Results from the follow up measures (see Table 3) revealed that results from post-treatment were sustained at a one-year follow-up with within-group effect-sizes ranging from d = 1.00–0.53, with a mean of d = 0.71, indicating that the treatment had sustained effects one year after completion. On the primary measure (CORE-OM), 33.3% (25/75) showed a clinical significant improvement one year after completion. If non responding persons would be regarded as treatment failures, these figures would have changed to 27.2% (25/92). Table 3. Estimated means, standard error (SE), standard deviation (SD) on all outcome measures at pre-treatment, post-treatment and one-year follow up, and within-group Cohen’s effect sizes (d) at one-year follow-up. Measure Time Estimated means (SE) SD p (time) Significant pairwise comparisons Within-group d CORE-OM Pre 15.634 (.494) 4.74 p < .000 Pre > Post = 1 yr 0.75 Post 11.314 (.579) 5.55 1Fup 11.487 (.643) 6.17 BAI Pre 16.559 (.920) 8.82 p < .000 Pre > Post = 1 yr 0.53 Post 12.312 (.746) 7.16 1Fup 11.941 (.914) 8.77 MADRS-S Pre 18.098 (.722) 6.93 p < .000 Pre > Post = 1 yr 1.00 Post 10.603 (.837) 8.03 1Fup 10.550 (.851) 8.16 QOLI Pre .703 (.145) 1.39 p < .000 Pre > Post = 1 yr 0.57 Post 1.491 (.155) 1.49 1Fup 1.597 (.182) 1.75 Abbrevations: CORE-OM Outcomes in Routine Evaluation – Outcome Measure; BAI, Beck Anxiety Inventory; MADRS-S, Montgomery Åsberg Depression Rating Scale-Self rated; QOLI, Quality of Life Inventory; SE, standard error; SD, Standard deviation. Table options Further exploration of interaction effects of comorbid mood disorder revealed no moderating effect on the CORE-OM (F (1,77.974) = 2.353, p = .102) or on the BAI (F (1,75.120) = 1.301, p = .278) or the MADRS-S (F (1,71.172) = 2.492, p = .090). There was a significant interaction effect of time and mood disorder on the QOLI, however (F (1,67.021) = 3.969, p = .023). This indicates that patients with a comorbid mood disorder had a larger gain in their quality-of-life assessments from pretreatment to one year follow-up. Psychological treatment and medication At the one-year follow-up, based on observed data (n = 75), 36% (27/75) reported that they had started another psychological treatment for their condition, and 16% (12/75) reported increasing or starting anxiolytic or antidepressant medication. A majority 90.7% (68/75) reported no changes in medication, and 12% (9/75) reported lowering their dosage. In these data the persons not using anxiolytic or antidepressant medication at baseline were reported as “no changes in medication” if this had not changed. Divided into the original groups 31% (13/42) of the treatment group started an additional psychological treatment, 16.3% (7/42) increased or started medication, 9.5% (4/42) decreased or stopped and 69.1% (29/42) reported unchanged medication. In the control group 39.4% (13/33) started an additional psychological treatment, 3% (1/33) increased or started medication, 6.1% (2/33) decreased and 51.5% (17/33) reported no changes in medication. No differences were found on altering medication (χ2(2) = .952, p = .621) or starting psychological treatment (χ2(1) = .319, p = .572) between the two groups. Costs Table 4 presents the per capita costs at baseline, post-treatment, and at a 12-month follow-up. Analysis of change in gross total costs from baseline to post-treatment showed a significant interaction effect of time and group, indicating that the ICBT group made larger cost reductions than the control condition (F (1,95) = 7.80; p = .006). Analysis of subtype of the cost domain revealed that this effect was primarily driven by larger indirect cost reductions in the ICBT group compared to the control condition (F (1,95) = 7.54; p = .007). There were no significant interaction effects of group and time in the other cost domains ((F (1,95) = 0.41–1.42); p = .24–53). Within-group tests showed that participants who received ICBT made significant gross total cost reductions from baseline to post-treatment (t(47) = 3.23; p = .002), and from baseline to the 12-month follow-up (t(40) = 4.02; p < .001), indicating stability of cost reductions. Participants in the control condition did not significantly reduce their gross total at post-treatment compared to baseline (t(47) = −0.94; p = .35). The intervention costs per participant were estimated to be $507 for ICBT and $68 for the control condition. Table 4. Per capita costs in US Dollars at pre-treatment, post-treatment and 1-year follow-up. Cost data at each assessment point. Cost Pre-treatment Post-treatment 1-Year follow-up ICBT CC ICBT CC ICBT CC Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Direct medical 333 357 257 305 234 397 215 399 250 543 229 309 Health care visits 322 354 250 303 224 395 210 397 246 543 225 308 Medication 11 27 7 12 9 24 6 12 5 7 4 7 Direct non-medical costs 73 190 42 69 83 158 86 172 73 204 22 51 Indirect costs 2142 1691 1505 1593 1443 1668 1776 1787 1100 1499 995 1450 Unemployment 1674 1784 1073 1644 1177 1697 1376 1767 827 1533 666 1412 Sick leave 214 608 193 626 124 559 199 893 70 190 251 704 Work cutback 104 311 160 388 77 198 120 341 127 321 45 127 Domestic 150 231 78 98 65 111 74 107 77 148 33 52 Gross total costs 2548 1812 1803 1694 1757 1870 2078 1868 1423 1806 1247 1501 Intervention costs 507 68 507 575 Net total costs 2264 2146 1930 1822 Abbreviations: ICBT, Internet-based cognitive behavior therapy; CC, control condition. Note: at 1-year follow-up, participants in the control condition had received ICBT. Table options Cost-effectiveness At post-treatment, the incremental cost-effectiveness ratio (ICER) was −616/0.34 = −$1824, favoring ICBT over the control condition. This meant that each incremental improvement on CORE-OM for participants in ICBT relative to the control condition generated a societal earning of $1824. This gain was because the total net costs were lower in the ICBT condition compared to the control condition and because clinically significant improvements were more likely to occur in the ICBT condition. The scatter of simulated ICERs across the four quadrants of the ICER plane indicated the degree of uncertainty around the ICER (see Fig. 2 in the Supplementary Material online). From a cost-effectiveness perspective, the most favorable outcome is a concentration of scatter in the southeast quadrant, indicating superior treatment effects and lower costs of the experimental treatment (ICBT) compared to the control condition. A concentration of ICERs in the southwest quadrant would indicate lowered treatment effects and lowered costs of ICBT compared to the control condition. If a majority of the simulated ICERs appeared in the northwest quadrant, ICBT would be associated with higher costs and lowered effectiveness compared to the control condition, thus making it unacceptable from a cost-effectiveness perspective. A majority of the simulated ICERs are located in the southeast quadrant (95.3%), indicating that ICBT is highly cost-effective compared to the control condition. The same data are used to plot the acceptability curve (see Fig. 3 in the Supplementary Material online for a graphic vision of the curve). The curve indicates that ICBT has a 95% probability of being cost-effective if society was willing to pay $0 for one additional improved patient. If society was willing to pay $1000 for one case of improvement, the probability of ICBT being cost-effective would increase to 99%. Cost-utility analysis At post-treatment, the cost-utility ICER was −474/0.063 = −$7523. This meant that one additional QALY generated a societal earning of $7523 when comparing ICBT to the control condition. A majority of the cost-utility ICERs are located in the southeast quadrant of the ICER-plane (77%), suggesting that the most probable outcome is that ICBT leads to additional QALYs while producing societal cost reductions. Of the remaining cost-utility ICERs, 13.7% are located in the southwest quadrant, 7.5% in the northeast quadrant, and 2.1% in the northwest quadrant (see Fig. 4 in the Supplementary Material online). The same data are used for the acceptability curve (see Fig. 5 in the Supplementary Material online). The curve indicates that ICBT has a 90% probability of being cost-effective if the society would pay $0 for one gained QALY. If the society were willing to pay $3000 for one additional QALY, the probability of ICBT being cost-effective would increase to 95%. Sensitivity analyses The acceptability curves assuming additional costs of ICBT ($200 and $600) correspond to (a) a scenario of low productivity and (b) a scenario assuming the cost of ICBT during the first year of delivering the service. The latter analyses included all one-time costs of development of ICBT and establishing the treatment in a health-care context. ICBT would remain the most cost-effective treatment if $200 were added to the costs of ICBT even if willingness to pay for an additional case of improvement were $0. If $600 were added to the intervention cost, ICBT would be most likely to be cost-effective even if the willingness to pay was $0 if using clinically significant improvement as ICER outcome (Fig. 3). If adding $600 to the costs of ICBT and using QALY as outcome, the treatment would have a 37% probability of being cost-effective in comparison to no treatment if willingness to pay for an additional QALY was $0. This probability would increase to 60% if society were willing to pay $3500 for one additional QALY.