Intervenciones para el tratamiento de la fatiga en adultos con un tumor cerebral primario
Referencias
Referencias de los estudios incluidos en esta revisión
Referencias de los estudios excluidos de esta revisión
Referencias de los estudios en espera de evaluación
Referencias de los estudios en curso
Referencias adicionales
Referencias de otras versiones publicadas de esta revisión
Characteristics of studies
Characteristics of included studies [ordered by study ID]
| Study characteristics | ||
| Methods | Double‐blind randomised placebo‐controlled trial | |
| Participants | Inclusion criteria: aged ≥ 18 years; diagnosed with a histologically confirmed glioma or meningioma; no signs of tumour recurrence in last 6 months; fatigue self‐reported CIS score > 27 Exclusion criteria: history of psychiatric disease or symptoms; expected adverse interactions between prescribed medications and modafinil; unable to communicate in Dutch Number randomised: modafinil: 20; placebo: 17 Age: 48.16 (SD 12.02) years Sex: 62.2% women; 37.8% men Tumour type: meningioma (32.4%), low‐grade glioma (37.8%) or high‐grade glioma (29.7%) Previous treatment: surgery (94.6%), without further radiotherapy (56.8%) or chemotherapy (78.4%) Follow‐up: 6 weeks and 12 weeks Setting: 3 centres in the Netherlands | |
| Interventions | 2 treatment arms for 6 weeks' duration Arm I treatment schedule Week 1: oral modafinil 200 mg per day in 2 divided does (100 mg upon waking, 100 mg at lunchtime) Week 2–6: oral modafinil 400 mg per day in 2 divided doses (200 mg upon waking, 200 mg at lunchtime) Week 7: washout period Week 8–12: matched placebo Arm II treatment schedule Week 1–6: matched placebo Week 7: washout period Week 8: oral modafinil 200 mg per day in 2 divided does (100 mg upon waking, 100 mg at lunchtime) Week 9–12: oral modafinil 400 mg per day in 2 divided doses (200 mg upon waking, 200 mg at lunchtime) | |
| Outcomes | Fatigue (CIS) Depression (Center for Epidemiologic Studies Depression Scale) Health‐related quality of life (Medical Outcomes Study Short‐Form Health Survey) Subjective cognitive functioning (Medical Outcomes Study subjective cognitive functioning scale) Objective cognitive functioning (Rey Auditory Verbal Learning Test, Memory Comparison Test, Stroop Colour Word Test, Letter Digit Substitution Test, Concept Shifting Test, Categorical Word Fluency Test, Concept Shifting Test) | |
| Notes | Mean imputation used where missing values were present in questionnaires or neuropsychological assessments. No corrections for multiple statistical testing carried out. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "A pharmacy randomization system was used to assign participants". Comment: confirmed via correspondence. |
| Allocation concealment (selection bias) | Low risk | Quote: "A pharmacy randomization system was used to assign participants". Comment: confirmed via correspondence. |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "Patients, treating physicians, and researchers were blind to treatment allocation". Comment: confirmed via correspondence. |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "Patients, treating physicians, and researchers were blind to treatment allocation". Comment: confirmed via correspondence. |
| Incomplete outcome data (attrition bias) | Unclear risk | Unclear how much imputation may have affected the result as sensitivity analysis was not carried out to determine whether missing data altered the results of the review. Similar number of participants dropped out between time points baseline and 6‐week follow‐up (modafinil arm: 4 participants; placebo arm: 3 participants), more participants dropped out of placebo arm (4 participants) than modafinil arm (1 participant) between 6‐week follow‐up and 12‐week follow‐up. Mean imputation was used where missing values were present in questionnaires or neuropsychological assessments. Details of adverse events per group confirmed through correspondence with the lead author. 5 participants dropped out due to adverse events while receiving modafinil. Details per participant were:
2 participants dropped out of the trial due to adverse events while receiving placebo. Details per participant were:
|
| Selective reporting (reporting bias) | Low risk | All outcomes reported. |
| Other bias | Low risk | None. |
| Study characteristics | ||
| Methods | Double‐blind, randomised placebo‐controlled trial | |
| Participants | Inclusion criteria: aged ≥ 18 years; KPS > 60; diagnosed with a histologically confirmed and stable PBT; ≥ 3 months since radiotherapy with or without (concurrent) chemotherapy; severe self‐reported fatigue on the 20‐item Multidimensional Fatigue Inventory (score ≥ 60) Exclusion criteria: treatable fatigue; other symptoms impacting test completion (e.g. severe aphasia); contraindications for amphetamines; co‐occurring depression (assessed as a HADS score > 8) Number randomised: dexamfetamine: 23; placebo: 23 Age (mean): intervention: 55 years; control: 49 years Sex: women (48.8%); men (51.2%) Tumour type: high‐grade glioma (75.6%), low‐grade glioma (7.3%), CNS lymphoma (9.7%) and medulloblastoma (7.3%) Previous treatment: radiotherapy + chemotherapy: 34 participants; radiotherapy alone: 3 participants; chemotherapy alone: 4 participants Follow‐up: 3 months Setting: multi‐institutional in France | |
| Interventions | 2 arms for 3 months' duration Arm 1 treatment schedule Day 1–10: dexamfetamine 10 mg in divided doses (5 mg in the morning, 5 mg at noon) Day 11–20: if previous dose tolerated, dexamfetamine 20 mg in divided doses (2 × 5 mg in the morning, 2 × 5 mg at noon) Day 21–30: if previous dose tolerated, dexamfetamine 30 mg taken in divided doses (3 × 5 mg in the morning, 3 × 5 mg at noon) Day 31: if previous dose tolerated, dexamfetamine 30 mg dose continued to 3‐month endpoint. If not tolerated, dexamfetamine 10 mg taken in divided doses until 3‐month endpoint Arm II placebo schedule Day 1–10: 2 × identical‐appearing tablets (1 × in the morning, 1 at noon) Day 11–20: if previous dose tolerated, 4 × identical‐appearing tablets (2 × in the morning, 2 at noon) Day 21–30: if previous dose tolerated, 6 × identical‐appearing tablets (3 × in the morning, 3 at noon) Day 31: if previous dose tolerated, 6 × identical‐appearing tablets continued to 3‐month endpoint | |
| Outcomes | Fatigue (20‐item Multidimensional Fatigue Inventory) Depression (HADS) Quality of Life (EORTC QLQ‐C30/EORTC QLQ‐BN 20) Cognition (Mattis Dementia Rating Scale, Verbal Fluency‐Category test, Trail Making Test Parts A and B, Wisconsin Card Sorting Test, Marin Apathy Scale, Grober and Buschke test Toxicity and adverse events (Norris Scale) | |
| Notes | Did not state any use of imputation for missing data. No corrections for multiple statistical testing carried out. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Manuscript did not mention how the randomisation was performed and there was no reported analysis to assess whether the 2 groups were different at baseline. |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding of participants and personnel (performance bias) | Low risk | Identical‐appearing tablets and dose schedule. |
| Blinding of outcome assessment (detection bias) | Low risk | Stated double‐blind methodology used. Probably done. |
| Incomplete outcome data (attrition bias) | Low risk | High retention rate 89% with reasons for drop‐out specified:
|
| Selective reporting (reporting bias) | Low risk | Data not analysed for 1 cognitive test due to about 50% missing data. All other outcomes reported. |
| Other bias | Low risk | None. |
| Study characteristics | ||
| Methods | Double‐blind randomised placebo‐controlled trial | |
| Participants | Inclusion criteria: adults diagnosed with a high‐grade glioma; ≥ 4 weeks following radiotherapy; previous surgery or biopsy with concurrent radiotherapy and chemotherapy; clinically stable or improved KPS compared to previous month; stable dose of corticosteroids; fatigue self‐reported > 6 on the 'worst' item of the BFI Exclusion criteria: pregnancy Number randomised: armodafinil 150 mg: 103; armodafinil 250 mg: 97; placebo: 97 Age: 57.3 (SD 12.3) years Sex: women: 41.2%; men: 58.8% Tumour type: clinically stable high‐grade glioma; no further details Previous treatment: completed radiotherapy but ongoing chemotherapy was allowed; no further details Follow‐up: 4 weeks and 8 weeks Setting: USA | |
| Interventions | 2 treatment arms, 1 placebo arm, for 8 weeks' duration Arm I treatment schedule Oral armodafinil 150 mg taken in the morning for 8 weeks Arm II treatment schedule Oral armodafinil 250 mg taken in the morning for 8 weeks Arm III placebo schedule Oral placebo taken in the morning for 8 weeks | |
| Outcomes | Fatigue (BFI) Health‐related quality of life (Linear Analogue Self‐Assessment) Objective cognitive functioning (Symbol Digit Modalities Test) Adverse events (Common Terminology Criteria for Adverse Events Version 4.0) | |
| Notes | Data not yet published – data available via ClinicalTrials.gov | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | There was no mention how the randomisation was performed and there was no reported analysis to assess whether the 2 groups were different at baseline. |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding of participants and personnel (performance bias) | Low risk | Double‐blind methodology reported. Probably done. |
| Blinding of outcome assessment (detection bias) | Unclear risk | No details provided. |
| Incomplete outcome data (attrition bias) | Unclear risk | No details of reasons missing data. |
| Selective reporting (reporting bias) | Low risk | All outcomes reported. |
| Other bias | Low risk | None. |
BFI: Brief Fatigue Inventory; CIS: Checklist Individual Strength; EORTC QLQ‐BN 20: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Brain Neoplasm; EORTC QLQ‐C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐C30; HADS: Hospital Anxiety and Depression Scale; KPS: Karnofsky Performance Scale; PBT: primary brain tumour.
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. No control group. | |
| Fatigue was not a necessary inclusion criterion. | |
| Fatigue was not a necessary inclusion criterion. No control group. |
Characteristics of studies awaiting classification [ordered by study ID]
| Methods | Randomised controlled feasibility trial |
| Participants | Inclusion criteria: adults aged ≥ 18 years diagnosed with a primary brain tumour; ≥ 3 months since radiotherapy or chemotherapy (or both); clinically and radiologically stable; self‐reported fatigue > 4 on Brief Fatigue Inventory Exclusion criteria: inability to give informed consent; clinically unstable; radiological progression; significant cognitive or sensory impairment Number randomised: 46 Follow‐up: after interventions and at 16 weeks Setting: 4 centres across the UK |
| Interventions | 2 treatment arms and 1 self‐guided support arm, of 16 weeks Arm I 'Health Coaching' schedule Participants received an information leaflet and 'Health Coaching', which involved an individualised programme based on physical measurements and lifestyle information. Participants wore an activity monitoring device and recorded information in a diary. Participants were offered 5 × 45‐minute Health Coaching sessions (delivered remotely or in person) focused on setting personal goals to change lifestyle factors contributing to fatigue. Arm II 'Health Coaching plus Patient Activation' schedule Participants received the same intervention as in arm I plus Patient Activation. Participants were offered 2 × 1‐hour Patient Activation sessions, delivered by a trained coach, focused on improving their approach to managing fatigue. Arm III control schedule Participants were given fatigue management information alongside treatment as usual. |
| Outcomes | Feasibility (participant recruitment and retention, acceptability, manageability) Fatigue (Brief Fatigue Inventory) Depression (Hospital Anxiety and Depression Scale) Quality of Life (Psychological Outcome Profiles) |
| Notes | Data not yet published |
Characteristics of ongoing studies [ordered by study ID]
| Study name | Effects of two types of exercise training on psychological well‐being, sleep, quality of life and physical fitness in patients with high‐grade glioma (WHO III and IV): study protocol for a randomized controlled trial |
| Methods | Randomised controlled clinical trial Participants randomly assigned to receive 1 of 2 exercise courses or to a control group |
| Participants | Inclusion criteria: adults aged 18–75 years with a diagnosis of high‐grade glioma, following treatment (surgery with radiotherapy or chemotherapy, or both) Exclusion criteria: diagnosis of severe psychiatric disorder or severe health comorbidities (e.g. severe diabetes, severe cardiovascular disease) |
| Interventions | Arm 1: endurance training for 2 × 40‐ to 60‐minute sessions per week for 6 weeks Arm 2: resistance training for 2 × 40‐ to 60‐minute sessions per week for 6 weeks Arm 3: control group – individualised counselling "not intended to actively improve participants' well‐being" (taken from clinicaltrials.gov/ct2/show/NCT03775369) |
| Outcomes | Self‐reported fatigue (Functional Assessment of Cancer Therapy – Fatigue, Fatigue Severity Scale) Self‐reported depression (Hamilton Depression Rating Scale) Self‐reported intolerance of uncertainty (Intolerance of Uncertainty Scale) Self‐reported measure of insomnia (Insomnia Severity Index) Self‐reported stress (Perceived Stress Scale) Self‐reported mental toughness (Mental Toughness Questionnaire) Self‐reported physical activity (International Physical Activity Questionnaire) Objective walking capacity (6‐minute walking test) Objective grip strength (grip force) Other measures: Change in sleep continuity and sleep architecture (assessed by electroencephalogram) Change in C reactive protein (assessed by blood test) |
| Starting date | 2018 |
| Contact information | Serge Brand: [email protected] Dominik Cordier: [email protected] Tel: 161‐2074‐782 |
| Notes | ClinicalTrials.gov identifier: NCT03775369 Current status: recruiting |
| Study name | The Vitality Project for fatigued female cancer survivors |
| Methods | Double‐blind randomised controlled trial Participants randomly assigned to receive 1 of 2 courses: 2 hours and 15 minutes twice weekly of qigong (mind–body movement) or healthy living (nutrition and exercise) classes |
| Participants | Inclusion criteria: women aged 18–70 years; cancer treatment completed ≥ 8 weeks prior to enrolment, including chemotherapy, radiotherapy, surgery, or a combination of these; ≥ 3/10 on self‐reported measure of fatigue interference in daily life; understands English; willingness to complete EEG, ECG, EMG and fMRI, and questionnaires, and have blood drawn; able to pass basic physical movement assessment to verify safety for enrolment into the study Exclusion criteria: history of coronary artery or coronary heart disease, myocardial infarction or heart murmur; pacemaker implant; peripheral neuropathy in hands; history of a major psychiatric disorder, not including depression or anxiety; active substance misuse; tobacco use; pregnancy; consumption of caffeine or cocoa products within 2 hours prior to data collection; inability to complete gentle exercise Follow‐up: after 10‐week intervention, and 3 months after intervention Setting: USA |
| Interventions | Arm 1: 2 hours and 15 minutes twice weekly qigong classes, focusing on mind–body movement, for 10 weeks Arm 2: 2 hours and 15 minutes twice weekly healthy living counselling focusing on nutrition, and aerobic and strengthening exercise, for 10 weeks |
| Outcomes | Self‐reported fatigue (FACIT‐Fatigue Scale, Fatigue Symptom inventory) Physical measurements (ECG, impedance cardiography, EEG, tactile acuity, EMG, precision grip, electrodermal activity, mechanical lung function, inflammatory cytokines, resting state fMRI, muscle strength, 6‐minute walk test) Objective measure of cognition (short‐form OSpan (operation span)) Self‐reported anxiety and depression (Patient Health Questionnaire, Profile of Mood States Questionnaire) Self‐reported emotional dysregulation (Difficulties in Emotion Regulation Scale) Self‐reported physical, social, emotional and functional well‐being (FACT‐G) Self‐reported quality of life (Rand 36‐item Short Form Health Survey) Self‐reported sleep quality, habits and patterns (Pittsburgh Sleep Quality Index) Heart rate and step count (via Apple watch) Self‐reported stress (Perceived Stress Scale) Self‐reported social support (Multidimensional Scale of Perceived Social Support) Self‐reported tendency to care for others before themselves (Unmitigated Communion Scale) Self‐reported quantity of exercising and relaxing (Godin Leisure time questionnaire) |
| Starting date | 2017 |
| Contact information | Ellen Flynn Miriam Hospital Outpatient, Providence, RI, USA Tel: +1 401‐793‐7020; email: [email protected] |
| Notes | ClinicalTrials.gov Identifier: NCT03259438 Current status: unknown as of November 2021 |
| Study name | Cognitive behavioral therapy in treating severe fatigue in patients with primary brain tumors – a randomized controlled clinical trial |
| Methods | Randomised controlled trial Psychological intervention or control group |
| Participants | Inclusion criteria: adults aged > 18 years with a histological diagnosis of PBT; with stable disease; ≥ 2 months since active treatment; expected survival ≥ 3 months; able to read, write and speak Dutch; and scoring over a clinical cut‐off score for severe fatigue on the CIS‐20 Exclusion criteria: other causes of fatigue not related to brain tumour treatment or receiving pharmacological treatment for fatigue in the past 3 months. Those experiencing depression, primary sleep disorders, receiving psychological intervention for a psychiatric disorder, currently (or within 3 months of being) pregnant or a KPS score < 70 |
| Interventions | Arm 1: cognitive behaviour therapy involving therapist sessions and online modules, for 12 weeks Arm 2: control group (details unknown) |
| Outcomes | Self‐reported fatigue (CIS – Fatigue score) Self‐reported depression, anxiety and health‐related quality of life Objective measure of neurocognitive functioning |
| Starting date | 2020 |
| Contact information | Jantine Röttgering Tel: +31 020‐4448‐453; email: [email protected] |
| Notes | Netherlands Trial Register identifier: NL8711 Current status: unknown |
CIS‐20: 20‐item Checklist Individual Strength; ECG: electrocardiogram; EEG: electroencephalogram; EMG: electromyography; FACIT‐F: Functional Assessment of Chronic Illness Therapy – Fatigue; FACT‐G: Functional Assessment of Cancer Therapy – General; fMRI: functional magnetic resonance imaging; KPS: Karnofsky Performance Scale; PBT: primary brain tumour; WHO: World Health Organization.
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Fatigue Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.1  Comparison 1: Boele 2013: modafinil versus placebo, Outcome 1: Fatigue | ||||
| 1.1.1 Concentration problems | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐1.06 [‐3.18, 1.06] |
| 1.1.2 Reduced motivation | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐0.48 [‐2.93, 1.97] |
| 1.1.3 Reduced activity | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐1.01 [‐5.64, 3.62] |
| 1.1.4 Fatigue severity | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐0.22 [‐0.79, 0.35] |
| 1.2 Objective cognitive functioning Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.2  Comparison 1: Boele 2013: modafinil versus placebo, Outcome 2: Objective cognitive functioning | ||||
| 1.2.1 Verbal memory | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.26 [‐0.05, 0.57] |
| 1.2.2 Working memory | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.07 [‐0.04, 0.18] |
| 1.2.3 Attentional functioning | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | ‐0.03 [‐0.05, ‐0.01] |
| 1.2.4 Information processing | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.17 [‐1.19, 1.53] |
| 1.2.5 Executive functioning | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐9.33, 9.61] |
| 1.2.6 Psychomotor speed | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.26, 0.46] |
| 1.3 Subjective cognitive functioning Show forest plot | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | 1.62 [‐0.74, 3.98] |
| Analysis 1.3  Comparison 1: Boele 2013: modafinil versus placebo, Outcome 3: Subjective cognitive functioning | ||||
| 1.4 Depression Show forest plot | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | Not estimable |
| Analysis 1.4  Comparison 1: Boele 2013: modafinil versus placebo, Outcome 4: Depression | ||||
| 1.5 Health‐related quality of life Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.5  Comparison 1: Boele 2013: modafinil versus placebo, Outcome 5: Health‐related quality of life | ||||
| 1.5.1 Physical | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | 1.34 [‐20.11, 22.79] |
| 1.5.2 Mental | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐1.40 [‐4.84, 2.04] |
| 1.6 Adverse events Show forest plot | 1 | 55 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.79 [0.59, 13.16] |
| Analysis 1.6  Comparison 1: Boele 2013: modafinil versus placebo, Outcome 6: Adverse events | ||||
Study flow diagram. RCT: randomised controlled trial.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: Boele 2013: modafinil versus placebo, Outcome 1: Fatigue
Comparison 1: Boele 2013: modafinil versus placebo, Outcome 2: Objective cognitive functioning
Comparison 1: Boele 2013: modafinil versus placebo, Outcome 3: Subjective cognitive functioning
Comparison 1: Boele 2013: modafinil versus placebo, Outcome 4: Depression
Comparison 1: Boele 2013: modafinil versus placebo, Outcome 5: Health‐related quality of life
Comparison 1: Boele 2013: modafinil versus placebo, Outcome 6: Adverse events
| Modafinil compared with placebo for fatigue in people with a primary brain tumour | ||||||
| Patient or population: people with a primary brain tumour Settings: hospital, outpatient Intervention: modafinil Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Placebo | Modafinil | |||||
| Fatigue –concentration problems Subscale from CIS range: 0–35 (follow‐up: 6 weeks) | The mean concentration problem score ranged across control groups from 15.91 to 23.91 points | The mean concentration problem score in the intervention groups was 1.06 lower (3.18 lower to 1.06 higher) | — | 37 (1) | ⊕⊝⊝⊝ | Higher scores indicate a higher level of concentration problems. |
| Fatigue –reduced motivation Subscale from CIS range: 0–28 (follow‐up: 6 weeks) | The mean reduced motivation score ranged across control groups from 10.22 to 19.48 points | The mean reduced motivation score in the intervention groups was 0.48 lower (2.93 lower to 1.97 higher) | — | 37 (1) | ⊕⊝⊝⊝ | Higher scores indicate lower motivation. |
| Fatigue –reduced activity Subscale from CIS range: 0–21 (follow‐up: 6 weeks) | The mean reduced activity score ranged across control groups from 3.84 to 21.34 points | The mean reduced activity score in the intervention groups was 1.01 lower (5.64 lower to 3.62 higher) | — | 37 (1) | ⊕⊝⊝⊝ | Higher scores indicate lower activity. |
| Fatigue –severity Subscale from CIS range: 0–56 | The mean fatigue severity score ranged across control groups from 34.06 to 36.22 points | The mean fatigue severity score in the intervention groups was 0.22 lower (0.79 lower to 0.35 higher) | — | 37 (1) | ⊕⊝⊝⊝ | Higher scores indicate a higher level of fatigue. |
| Adverse events (follow‐up: 6 weeks) | Low‐risk population | RR 2.79 (0.59 to 13.16) | 37 (1) | ⊕⊝⊝⊝ | — | |
| — | 30 per 100 | |||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CIS: Checklist Individual Strength; CI: confidence interval; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded three levels; there was very low‐certainty evidence due to low accrual, such that recruitment did not meet the estimated power requirement to detect a true effect. | ||||||
| Dexamfetamine sulfate compared with placebo for fatigue in primary brain tumour | |||||
| Patient or population: people with a primary brain tumour Settings: hospital, outpatient Intervention: dexamfetamine sulfate Comparison: placebo | |||||
| Outcomes | Median change from baseline (IQR) | Between‐group comparison | No. of participants | Certainty of the evidence | Comments |
|---|---|---|---|---|---|
| Placebo | dexamfetamine sulfate | ||||
| Fatigue MFI‐20 scale (follow‐up: 3 months) | The median difference in fatigue score between baseline and 3‐month follow‐up in the control group was 14 points (IQR 4.5 to 24.25) | The median difference in fatigue score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 4 points lower (IQR 4 to 13) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate a higher level of fatigue. |
| Fatigue ('asthenia') Norris Scale | The median difference in fatigue score between baseline and 3‐month follow‐up in the control group was 4.25 points (IQR –0.06 to 12.16) | The median difference in fatigue score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 2.31 points lower (IQR –10.88 to 13.96) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate a higher level of fatigue. |
| Cognition Trail Making Test A | The median difference in score between baseline and 3‐month follow‐up in the control group was 6.5 points (IQR –0.75 to 17.5) | The median difference in score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 7.5 points lower (IQR –4 to 10) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate poorer cognition. |
| Cognition Trail Making Test B | The median difference in score between baseline and 3‐month follow‐up in the control group was –2 points (IQR –16 to 21.75) | The median difference in score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 18 points higher (IQR –37 to 39) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate poorer cognitive performance. |
| Cognition Semantic Fluency | The median difference in score between baseline and 3‐month follow‐up in the control group was 1 points (IQR –1 to 3) | The median difference in score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 1 point lower (IQR –5 to 3) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate better cognitive performance. |
| Cognition Lexical Fluency | The median difference in score between baseline and 3‐month follow‐up in the control group was 1 point (IQR –0.75 to 2.75) | The median difference in score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 2 points lower (IQR –4 to 4) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate better cognitive performance. |
| Cognition Episodic memory (Grober and Buschke test) | The median difference in score between baseline and 3‐month follow‐up in the control group was –0.5 points (IQR –4.25 to 2.5) | The median difference in score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 0.5 points higher (IQR –4.5 to 4) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate better cognitive performance. |
| Cognition Mattis Scale | The median difference in score between baseline and 3‐month follow‐up in the control group was –2 (IQR –7 to 1) | The median difference in fatigue score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 1point higher (IQR –4 to 0) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate better cognitive performance. |
| Affectivity Norris Scale | The median difference in score between baseline and 3‐month follow‐up in the control group was 8.25 (IQR 2.34 to 18.09) | The median difference in score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 5.87 points lower (IQR –10.78 to 10) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate higher affectivity. |
| Apathy Marin Scale | The median difference in score between baseline and 3‐month follow‐up in the control group was 0.5 (IQR –6 to 2.75) | The median difference in score between baseline and 3‐month follow‐up in the dexamfetamine sulfate group was 1.5 points higher (IQR –2 to 11) | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicated higher apathy. |
| Depression HADS | — | — | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate more severe depression symptoms. |
| Quality of life EORTC QLQ‐C30 | — | — | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate better quality of life. |
| Quality of life EORTC QLQ‐BN 20 | — | — | 41 (1) | ⊕⊝⊝⊝ | Higher scores indicate better quality of life. |
| EORTC QLQ‐BN 20: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Brain Neoplasm; EORTC QLQ‐C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐C30; HADS: Hospital Anxiety and Depression Scale; IQR: interquartile range; MFI‐20: 20‐item Multidimensional Fatigue Inventory. | |||||
| GRADE Working Group grades of evidence | |||||
| aDowngraded three levels; there was very low‐certainty evidence due to low accrual, such that recruitment did not meet the estimated power requirement to detect a true effect. | |||||
| Armodafinil (150 mg and 250 mg) compared with placebo for fatigue | ||||||
| Patient or population: people with primary brain tumour Settings: hospital, outpatient Intervention: armodafinil (150 mg and 250 mg) Comparison: placebo | ||||||
| Outcomes | Group comparisons | No. of participants | Certainty of the evidence | Comments | ||
|---|---|---|---|---|---|---|
| Placebo | Armodafinil 150 mg | Armodafinil 250 mg | ||||
| Fatigue Brief Fatigue Inventory (number of participants with an improvement in 2 points from baseline at 8 weeks (%)) | 29 (29.9%) | 27 (27.8%) | 29 (28.2%) | 297 (1) | ⊕⊕⊝⊝ | Higher scores indicate higher fatigue. |
| Cognition Symbol Digit Modalities Test (median (range)) | 0.0 (–3.4 to 4.9) | 0.0 (–1.6 to 2.5) | 0.3 (–3.4 to 2.5) | 180 (1) | ⊕⊕⊝⊝ | Higher scores indicate better performance. |
| Quality of life Linear Analogue Self Assessment (median (range)) | 2.0 (–15.0 to 27.0 | 4.0 (–32.0 to 26.0) | 3.0 (–16.0 to 27.0) | 232 (1) | ⊕⊕⊝⊝ | Higher scores indicate better quality of life. |
| Adverse events Grade 3 or higher (number of participants (%)) | 3 (2.8%) | 6 (5.5%) | 8 (7.3%) | 328 (1) | ⊕⊕⊝⊝ | — |
| GRADE Working Group grades of evidence | ||||||
| aDowngraded two levels; there was low‐certainty evidence due to the level of unclear risk of bias relating to selection, detection and attrition. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Fatigue Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.1.1 Concentration problems | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐1.06 [‐3.18, 1.06] |
| 1.1.2 Reduced motivation | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐0.48 [‐2.93, 1.97] |
| 1.1.3 Reduced activity | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐1.01 [‐5.64, 3.62] |
| 1.1.4 Fatigue severity | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐0.22 [‐0.79, 0.35] |
| 1.2 Objective cognitive functioning Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.2.1 Verbal memory | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.26 [‐0.05, 0.57] |
| 1.2.2 Working memory | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.07 [‐0.04, 0.18] |
| 1.2.3 Attentional functioning | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | ‐0.03 [‐0.05, ‐0.01] |
| 1.2.4 Information processing | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.17 [‐1.19, 1.53] |
| 1.2.5 Executive functioning | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐9.33, 9.61] |
| 1.2.6 Psychomotor speed | 1 | 53 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.26, 0.46] |
| 1.3 Subjective cognitive functioning Show forest plot | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | 1.62 [‐0.74, 3.98] |
| 1.4 Depression Show forest plot | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | Not estimable |
| 1.5 Health‐related quality of life Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.5.1 Physical | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | 1.34 [‐20.11, 22.79] |
| 1.5.2 Mental | 1 | 55 | Mean Difference (IV, Fixed, 95% CI) | ‐1.40 [‐4.84, 2.04] |
| 1.6 Adverse events Show forest plot | 1 | 55 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.79 [0.59, 13.16] |
