**3. Practical applications**

As noted above, implementing iCBT in a primary-care setting would be important. To successfully do this, we must first understand how programs perform in the real world rather than the tightly controlled setting of a clinical trial. The REEACT trial was conducted in the UK, and considered how patients in a primary care setting could access iCBT (a pragmatic randomized controlled trial). The study included three groups of patients: those using a commercial program (Beating the Blues) in addition to general practitioner (GP) care, those using a free program (MoodGYM) in addition to GP care, and usual GP care (that is, access to antidepressants, counseling, psychological services, and secondary mental health services). Those patients who used iCBT also received weekly phone calls from trained technicians. In this trial, no differences in depressive symptoms or health state utility were observed between commercially available iCBT, free-to-use iCBT, and usual care. iCBT had a statistically significant benefit over usual care in the mental component of health-related quality of life and general psychological wellbeing at 12 months but not at 24 months. Even with telephone support, adherence was poor in both iCBT groups with only one completed session (as the median number of sessions completed). There was no observed advantage to using a commercially available program versus a free-to-use one [33]. Neither program was more cost effective than usual GP care [34]. When interviewed, participants liked the autonomy and flexibility of the program, but disliked the lack of interpersonal communication and customizability [35].

Because the patients in the REEACT trial expressed desire for more support, investigators conducted a second trial comparing the effectiveness of MoodGYM alone versus MoodGYM with telephone support (the REEACT-2 trial). The telephone support worker introduced patients to CBT, helped identify issues and set goals, motivated the patient, and discussed future steps. The study showed that telephone support made a difference, with significantly improved depression symptoms. The largest between-group difference was observed at 4 months (Cohen's d = 0.32), but the difference was no longer significant after 12 months. The odds ratio of not being depressed at 4 months was 2.05 (95% CI 1.23, 3.42; P = 0.0030) when telephone support was added to MoodGYM. There were also significant between-group differences in depression and anxiety scores. However, the adherence to the program did not increase substantially with 45% of patients completing the first session in the MoodGYM alone group and 65% completing the first session in the telephone-support group. An economic analysis indicated that telephone support could increase quality of life (in quality-adjusted life year [QALY]) and reduce healthcare costs with a likelihood of being cost effective at ₤6933 per QALY [36, 37].

While the literature is vast, a pattern is clear: iCBT can be effective. Even unguided iCBT, with its number needed to treat of eight, is beneficial to some patients [23]. But it should be noted that the number needed to treat jumps up to 2.56 for children and adolescents with anxiety using therapist-guided iCBT [30]. The emerging data on iCBT effectiveness and cost seem to support a stepped-care model, where patients with less severe illness and more motivation can be treated with unguided iCBT. As illness severity and desire for interaction increases, there is a role for iCBT programs with progressively more support. This model would balance the cost of treatment while providing the most benefit to individual patients and the population as a whole.
