Zeller 2014a.

Methods	Study design: case‐control study (follow‐up study of Hamre 2013a) Instrument used to assess severe fatigue: Fatigue Questionnaire Validated questionnaire: yes Cut‐off score or criterion for severe fatigue: sum score ≥ 4 for all 11 dichotomised items and duration of symptoms for ≥ 6 months Time points at which outcome data were collected: 2 time points, mean time between fatigue assessments 2.7 years (range 1 ‐ 4.3) Cases: n = 27; severe fatigue at both time points (persistent severe fatigue) Controls: n = 35; no severe fatigue at either time point Controls matched on diagnosis, age, gender Inclusion criteria: diagnosis between 1970 and 2002, age at diagnosis of 18 years and below (16 years and below for ALL), follow‐up time from diagnosis of at least 5 years, age at survey 18 years and above, participated in part 1 of the study (Hamre 2013a), did not change fatigue status (only for the risk factor analysis) Exclusion criteria: major somatic comorbidities, pregnancy (only for the risk factor analysis)
Participants	N of participants original cohort: unknown; N of participants described study group: 102; N of participants study group of interest: 102; N of participants fatigue assessed: 102a Tumour type: cases: lymphoma n = 14, ALL n = 13; controls: lymphoma n = 19, ALL n = 16 Tumour stage: nm Age at diagnosis: based on inclusion criteria, the maximum age at diagnosis is 18 years Time since diagnosis: cases: mean 23.0 years (SD 8.2), controls: mean 24.0 years (SD 7.9) Age at assessment: cases: mean 33.7 years (SD 6.6), controls: mean 34.4 years (SD 7.3) F/M: cases: 18/9, controls: 19/16 BMI: cases: mean 25.1 (SD 5.0), controls: mean 24.6 (SD 3.7) Race/ethnicity: nm Marital status: nm Highest completed education level: higher level of education ≥ 12 years, cases n = 11, controls n = 21 Employment: at present in paid work, cases n = 17, controls n = 26 Physical activity level: SF‐36 physical functioning scale, cases: median 80.0 (range 45 ‐ 100), controls: median 100 (range 70 ‐ 100). Number of steps per day, cases: mean 6861 (SD 2801), controls: mean 8687 (SD 2420) Sleeping problems: insomnia, cases n = 16, controls n = 7. Sleep duration in hours, cases: median 8 (range 3.5 ‐ 13), controls: median 7 (range 4 ‐ 9) Psychosocial problems: Anxiety (STAI), cases: median 49 (range 32 ‐ 70), controls: median 33 (range 23 ‐ 65) Depression (modified PHQ8), cases: median 7 (range 3 ‐ 21), controls: median 2.5 (range 0 ‐ 17) Comorbidities/late effects: Pain severity score (BPI), cases: median 10 (range 0 ‐ 28), controls: median 3.0 (range 0 ‐ 19) Genetic factors/mutations: nm
Interventions	N of participants radiotherapy: cases: n = 13, controls: n = 14 N of participants chemotherapy: nm N of participants surgery: nm Cumulative dosis anthracyclines: cases mean 166.2 mg (SD 139.9), controls mean 170.0 mg (SD 127.6)
Outcomes	Severe fatigue: N of participants with severe fatigue: at time point 1: 79/290 (27.2%); at time point 2: 41/102 (40.2%) N of participants with persistent severe fatigue: 32/102 (31.4%) Risk factors:b Dependent factor: persistent severe fatigue Univariable: Significant: depression (P < 0.001), insomnia (P = 0.002), pain severity score (P < 0.001), numbers of steps per day (P = 0.009) Non‐significant: radiotherapy (P = 0.437), time since diagnosis (P = 0.614), education (P = 0.102), employment (P = 0.246), BMI (P = 0.628) Multivariable: Significant: depression (OR 1.3 (95% CI 1.1 to 1.7), P = 0.014) Non‐significant: insomnia, pain severity score, numbers of steps per day
Notes	Funding sources: supported by the Norwegian Extra Foundation for Health and Rehabilitation Declaration of interest: The authors declare no conflict of interest a102 survivors participated in the second fatigue assessment, of which 62 were identified as case or control. bThe 62 cases and controls were included in the risk factor analyses. Univariable: Mann‐Whitney‐Wilcoxon test, independent sample t‐test or Chi2 test; multivariable: logistic regression. Only OR for depression was reported in the article
Risk of bias
Bias	Authors' judgement	Support for judgement
Representative study group (selection bias)	Unclear risk	Size of original cohort is unknown
Adequate follow‐up assessment (attrition bias)	Low risk	Outcome was assessed for > 95% of the study group of interest
Blinded outcome assessor (detection bias) All outcomes	High risk	Outcome assessors were not blinded to the investigated determinant
Adjustment important confounders	High risk	Follow‐up was not taken into account
Well‐defined study group (reporting bias)	High risk	Cancer type is mentioned and only radiotherapy is reported as cancer treatment. Inclusion and exclusion criteria are described
Well‐defined follow‐up (reporting bias)	Low risk	Length of follow‐up is mentioned
Well‐defined outcome severe fatigue (reporting bias) All outcomes	Low risk	The authors reported which instrument they used to assess fatigue and what they considered to be severe fatigue
Well‐defined outcome fatigue (reporting bias)	Low risk	Authors reported which instrument they used to assess fatigue, and how they described fatigue (persistent severe fatigue)
Well‐defined risk estimation	Unclear risk	Odds ratio is only provided for significant risk factor

AML: acute myeloid leukaemia; ALL: acute lymphoblastoma leukaemia; ASHQ: Adolescent Sleep Habits Questionnaire; b: regression coefficient; BCCSS: British Childhood Cancer Survivor Study; BMI: body mass index; BMT: bone marrow transplantation; BPI: Brief Pain Inventory; BSI: Brief Symptom Inventory; CCS: childhood cancer survivor; CCSS: Childhood Cancer Survivors Study; CDI: Childrens Depression Inventory; CES‐D: Center for Epidemiology Studies Depression scale; CES‐DC: Center for Epidemiology Studies Depression scale for Children; CHQ: Child Health Questionnaire; CNS: central nervous system; CRT: cranial irradiation; CSHQ: Childrens Sleep Habits Questionnaire; CT: chemotherapy; CTCAEv3: CommonTerminology Criteria for Adverse Events, Version 3; CUHK‐PARCY: Chinese University of Hong Kong: physical activity rating for children and youth; DIMS: disorder maintaining sleep; DOES: disorder of excessive somnolence; EORTC‐QLQ‐C30: European Organisation for Research and Treatment of Cancer Quality of Life core questionnaire; ESS: Epworth Sleepiness Scale; F: female; FACIT: Functional Assessment of Chronic Illness Therapy; GLTEQ: Godin‐Leisure‐Time Exercise Questionnaire; GVHD: graft versus host disease; Gy: Gray; HADS: Hospital Anxiety and Depression Scale; HL: Hodgkins lymphoma; HSCT: hematopoietic stem cell transplantation; IA: infratentorial astrocytoma; IQR: interquartile range; IT: intrathecal; IV: intravenous; M: male; NA: not applicable; ND: no data; NHL: non‐Hodgkins lymphoma; nm: not mentioned; OR: odds ratio; PedsQL: Pediatric Quality of Life; PHQ: Patient Health Questionnaire; PSQI: Pittsburgh Sleep Quality Index; r: correlation coefficient; REACH: Research Evaluating After‐Cancer Health project; RT: radiotherapy; SCL‐90‐R: Symptom Checklist‐90‐Revised; SCT: stem cell transplantation; SD: standard deviation; SE: standard error; SF‐36: Short Form ‐ 36; SHY:sleep hyperhydrosis; STAI: Spielberger Trait Anxiety Inventory; SWTD: sleep wake transition disorder; WT: Wilms tumour