641 patients were recruited, one of whom withdrew consent. Demographic and clinical characteristics of participants were similar across treatments, apart from a shorter duration of illness in SMC (). Costs and QALYs were available for 570 (89%) participants (ranging from 85% GET to 93% SMC). Those for whom both cost and QALY data were available were significantly more likely to be of Caucasian ethnicity (94.6% v 86.4%, fishers exact test p
0.027). There were no other statistically significant differences in the background characteristics shown in . Further details of the sample have been reported previously 
Baseline demographic and clinical data.
Service Use and Lost Employment before Randomisation
During the 6 months before randomisation, most participants had used primary care services and over 40% other (secondary care) doctors (). Around two-thirds had used other health service professionals, between one-quarter and one-third had used complementary healthcare practitioners; most used medication. The intensity of service use (mean contacts for those using them) revealed no substantial differences between treatment groups. Lost employment was common in all treatment groups.
Service use and lost employment at baseline and follow-up.
Service Use and Lost Employment after Randomisation
During the 12 months after randomisation, SMC participants had a higher mean number of specialist medical care contacts than those allocated to additional therapy. The number of therapy contacts did not differ between APT, CBT and GET groups. Other service use did not greatly differ between treatments during this period, although informal care hours for APT and SMC were higher than for CBT and GET. There was no clear difference between treatments in terms of lost employment.
Costs are shown in . Controlling for baseline, healthcare costs after randomisation were significantly lower for SMC than for APT (difference £840, 95% CI £637 to £1117), CBT (difference £904, 95% CI £613 to £1205) and GET (difference £829, 95% CI £534 to £1165). The differences between the APT, CBT and GET groups were small and non-significant.
Service costs at baseline and follow-up.
Informal care costs of patients allocated to APT were significantly higher than for CBT (difference £1580, 95% CI £139 to £3132) and GET (difference £1588, 95% CI £442 to £2694). Patients allocated to SMC also had higher informal care costs than CBT (difference £1165, 95% CI £289 to £2194) and GET (difference £1173, 95% CI £740 to £1569). Lost production costs were significantly higher for APT compared to CBT (difference £1279, 95% CI £141 to £2772). Societal costs (i.e. healthcare, informal care and lost production costs) were significantly lower for patients allocated to CBT compared to APT (difference £2607, 95% CI £432 to £5585). Other differences were not statistically significant.
Welfare Benefits and Other Financial Payments
Receipt of benefits due to illness or disability increased slightly from baseline to follow-up (). Patients in the SMC group had the lowest level of receipt at baseline but the figures at follow-up were similar between groups. Relatively few patients were in receipt of income-related benefits or payments from income protection schemes and differences between groups were not substantial.
N (%) receiving welfare benefits or other financial payments.
APT, CBT and GET each resulted in improvements in health-related quality of life (measured with the EQ-5D) while SMC produced little change (). CBT produced the largest QALY gain, significantly more than SMC. After controlling for baseline utility, the difference between CBT and SMC was 0.05 (95% CI 0.01 to 0.09). No other differences between treatment groups were statistically significant. The number (%) of patients achieving a clinically significant reduction in fatigue in each group was: APT 96 (64.0), CBT 113 (76.4), GET 123 (79.9), and SMC 98 (64.9). This difference was statistically significant (Fisher’s Exact test, p
0.002). The number (%) of patients achieving a clinically significant reduction in disability in each group was: APT 75 (49.0), CBT 105 (71.0), GET 108 (70.1), and SMC 88 (57.9). This difference was also statistically significant (Fisher’s Exact test, p<0.001).
EQ-5D utilities and QALYs accrued during follow-up period.
Cost-effectiveness from a Healthcare Perspective
At a threshold of £30,000 per QALY, CBT had a 62.7% likelihood of being the most cost-effective option from a healthcare perspective followed by GET at 26.8% (). APT had a 2.6% likelihood of being most cost-effective, which was less than the figure for SMC (7.9%).
QALY-based cost-effectiveness acceptability curves (healthcare perspective).
The ICERs showing the healthcare cost per QALY for CBT and GET compared to SMC were both below the threshold of £30,000 while the ICER for APT compared to SMC was substantially higher (). The healthcare costs per extra person with a clinically significant reduction in fatigue and disability are also shown. It is clear that achieving such a reduction for one person is associated with a much lower cost, compared to SMC, for CBT or GET than it is for APT. In fact, SMC dominates (i.e. has better outcomes and lower costs) APT with regard to disability.
Cost-effectiveness results from healthcare and societal perspectives, 0–52 weeks.
Cost-effectiveness from a Societal Perspective
Again at a threshold of £30,000 per QALY, CBT had a 59.5% likelihood of being the most cost-effective option from a societal perspective (). GET had a likelihood of 34.8% while APT and SMC had likelihoods of 0.2% and 5.5% respectively.
QALY-based cost-effectiveness acceptability curves (societal perspective).
CBT and GET both dominated SMC from a societal perspective with regard to QALYs gained and reductions in fatigue and disability. Compared to SMC, APT had an incremental cost per QALY substantially higher than the £30,000 threshold while the cost per person with a clinically significant reduction in fatigue was high. SMC dominated APT with regard to disability.
The healthcare costs per QALY gained for CBT and GET compared to SMC were below the cost-effectiveness threshold of £30,000. The cost of CBT would need to increase by 45% and GET by 22% for the cost per QALY to reach £30,000. Therapy costs for APT would need to fall 35% for APT to have a cost per QALY compared to SMC of £30,000. No other sensitivity analyses (i.e. changing the value of informal care, lost employment and standardised medical care) had a large impact on cost-effectiveness.