Evidence table for systematic reviews

Transcription

1 Evidence table for systematic reviews Topic: Nausea, vomiting, appetite und weight stimulation Reviewer: CMF, RK Abbreviations: AE adverse effects; CI confidence interval; MA meta-analysis; n.r. not reported; OR Odds ratio; RCT randomized controlled clinical trial; RD risk difference; RR risk ratio; SMD standard mean difference; SR systematic review; y - years Reference Research parameters Population Intervention Comparison Outcomes Additional comments Bibliographic Reference [1] Theo retic al appr oach [2] Study type and quality [3] Number of patients (studies) [4] Patient characteristics [5] Intervention [6] Comparison [7] Outcome measures and effect size [8] Comments (Source of funding) [9] OCEBM level of evidence [10] Risk of bias ROBIS [11] Mücke et al., 2016 SR and MA RCTs; study quality (according to risk of bias) was moderate (3 studies) to low (6 studies); 5 studies conducted in cancer patients (n = 758), 3 studies in HIV/AIDS patients (n = 251) and 1 study in Morbus Alzheimer patients (n = 15) 1561 (9) Patients diagnosed with progressed cancer (age: years), progressed HIV/AIDS (age: years) or progressed Alzhei er s disease (age: years); loss of weight and appetite or nausea or vomiting or pain due to progressed illness Dronabinol (5 7.5mg/day, max 20mg/day) (6 studies) Oral THC/CBD (5mg THC/ 2mg CBD/day) (1 study) Oral THC (5mg/day) (1 study) Mucosal THC/CBD ( mg/day THC/ mg/day CBD) (2 studies) Mucosal THC ( mg/day) (1 study) Cannabis (smoked) (max 3 cigarettes/day, 4% THC) Duration of treatment: median 6 weeks (HIV/AIDS), 8 weeks (cancer), 2x 6 weeks (Alzhei er s disease) Placebo (8 studies) Megestrol acetate ( mg/day) (2 studies) PAIN quality evidence; reduction of pain by 3 % ot sig ifi a tly etter with cannabinoids than placebo in cancer patients (RD: 0.07; 95 %-CI: ; p = 0,07) (2 studies) APPETITE/ WEIGHT quality evidence; pronounced stimulation of appetite due to cannabinoids (compared to placebo) in 4 studies revealed no statistical significance in MA (SMD = 0.65; 95% CI: ; p = 0.39); slightly stronger effects on appetite in HIV patients (SMD: 0.57; 95 %- CI: ; p = 0.02); no effects on bodyweight in cancer patients (1 study) but weight gain in HIV patients (2 studies) increased with dronabinol or smoked cannabis (SMD: 0.57; 95 %-CI: ; p = 0.001); slight but not significant increase in caloric intake (SMD: 0.2; 95 %- CI: ; p = 0.65); megestrol acetate more effective in weight gain and appetite stimulation than dronabinol (p < 0.02) (2 studies) Predominantly low quality studies; limited evaluation of long-term effects of cannabinoid treatment; small sample sizes in some studies 1 NAUSEA/ VOMITING quality evidence; slight but not significant improvement of nausea and vomiting in cancer and HIV/AIDS patients with cannabinoids compared to placebo

2 Reference Research parameters Population Intervention Comparison Outcomes Additional comments (3 studies) (SMD: 0.20; 95 %-CI: ; p = 0.09) TOLERABILITY/ SAFETY quality evidence; slightly but not significantly more dizziness/vertigo with cannabinoids (compared to placebo) in cancer patients (4 studies) (RD: 0.03; 95 %-CI: ; p = 0.23); risk of psychiatric adverse effects of cannabinoids not significantly different from placebo (5 studies) (RD: 0.01; 95 %- CI: ; p = 0.47) but significantly increased in HIV/AIDS patients (RD: 0.05; 95 %-CI: ; p = 0.05); emergence of severe adverse effects (RR: 1.2; 95 %-CI: ; p = 0.3) and study discontinuation due to drug intolerance (RR: 1.15; 95 %-CI: ; p = 0.3) was slightly but not significantly higher with cannabinoids compared to placebo > review of reviews > 4/6 SRs also conducted MA on 3 13 RCTs (Whiting et al. 2015, Smith et al. 2015, Tramer et al. 2001, Machado Rocha et al. 2008) > number of patients needed to treat (NNT) to achieve complete control of chemotherapy-induced nausea and vomiting (CINV) with CBs approximately 4:1 compared to placebo or conventional anti-emetics > common adverse effects of CBs: number of patients needed to harm (NNH) approximately 6:1 compared to placebo or conventional anti-emetics >this moderate quality evidence suggests a small therapeutic window for CBs in CIMV > lack of comparative studies for CBs and ew ge eratio a ti-emetics and CBs for adjunctive treatment with standard therapy > proposing CBs for 3 rd or 4 th line medication in CINV specifically in patients with break-through or refractory CINV Tafelski et al., 2016 SR 6 SRs and MAs of moderate to high quality including a total of 43 RCTs N =? (43) Infant and adult patients (3.5 82y) with different types of cancer undergoing a variety of chemotherapeu tic regimens with moderate to high emetic potential Oral Nabilone (1-7 mg/day) (18 studies) Oral Dronabinol (7.5-30mg/day) (17 studies) Intramuscular Levonantradol (1.5-3mg/day) (4 studies) CB plant extract (1 study) Placebo, Antipsychotics (prochlorpera zine, thiethylperazi ne, chlorpromazi ne, haloperidol), Prokinetics (metoclopra mide, domperidone ), Dopamine antagonists (alizapride), Anticonvulsa nts (gabapentin), Steroids (dexamethas one), ondansetron > Majority of trials conducted between and does not represent state-of-the-art chemotherapeutic regimens and anti-emetic comparator therapy (5-HT3 or NK1 receptor antagonists) > no update literature search conducted for RCTs being published after the latest SR 1 Whiting et al., 2015 SR and MA See below See below See below See below funded by the Swiss Federal Office of Public Health (FOPH) under grant agreement 1

3 Reference Research parameters Population Intervention Comparison Outcomes Additional comments RCTs 3 Parallel group 1 cross-over 255 (4) (4 reports) HIV/AIDS: Antiretroviral regimen, loss of bodyweight Cannabis (smoked)(max 3 cigarettes/day, 4% THC) (1 study); Dronabinol (5mg- 10mg/day) (4 studies) Placebo, megestrol acetate (750mg/day) There was some evidence that dronabinol is associated with an increase in weight when compared with placebo. Predominantly low quality studies High risk of bias; limited evaluation of long-term effects of cannabinoid treatment; small sample sizes in some studies RCTs 21 Cross-over 7 Parallel group 23 high risk of bias 1772 (28) (37 reports) Cancer patients, Nausea and vomiting due to chemotherapy Nabilone (Cesamet)(max 10mg/day) (14 studies); THC (max 50mg/day, max. 14mg/m² every 4h) (6 studies); Nabiximols (sativex)(max 8 sprays in any 4h period/24h) (1 study); Levonantradol (IM) (max 4mg/day) (4 studies); Dronabinol (marinol)(max 40mg/day) (3 studies) Proclorperazi ne, Hydroxizine, Domperidone, Placebo, Chlorpromazi ne, Metoclopram ide, Alizapride All studies suggested a greater benefit of cannabinoids for complete control of chemotherapy-induced nausea and vomiting compared with both active comparators and placebo, but these did not reach statistical significance in all studies.the average number of patients showing a complete nausea and vomiting response was greater with cannabinoids (dronabinol or nabiximols) than placebo (47% vs 20%,OR, 3.82 [95% CI, ]; 3 trials). Predominantly low quality studies; 5 unclear risk of bias, limited evaluation of long-term effects of cannabinoid treatment; small sample sizes in some studies 25 of 28 studies were > 25 years old, only 1 study with firstline medication as comparator

4 ROBIS: Tool to assess risk of bias in systematic reviews Mücke et al Phase 1: Assessing relevance (Optional) ROBIS is designed to assess the risk of bias in reviews with questions relating to interventions, aetiology, diagnosis and prognosis. State your overview/guideline question (target question) and the question being addressed in the review being assessed: Intervention reviews: Patients/Population(s): Intervention(s): Comparator(s): Outcome(s): For aetiology reviews: Patients/Population(s): Exposure(s) and comparator(s): Outcome(s): For DTA reviews: Patients): Index test(s): Reference standard: Target condition: For prognostic reviews: Patients: Outcome to be predicted: Intended use of model: Intended moment in time: Does the question addressed by the review match the target question? YES/NO/UNCLEAR

5 Phase 2: Identifying concerns with the review process DOMAIN 1: STUDY ELIGIBILITY CRITERIA Describe the study eligibility criteria, any restrictions on eligibility and whether there was evidence that objectives and eligibility criteria were pre-specified: 1.1 Did the review adhere to pre-defined objectives and eligibility criteria? 1.2 Were the eligibility criteria appropriate for the review question? 1.3 Were eligibility criteria unambiguous? 1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? 1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Concerns regarding specification of study eligibility criteria DOMAIN 2: IDENTIFICATION AND SELECTION OF STUDIES Describe methods of study identification and selection (e.g. number of reviewers involved): 2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? 2.2 Were methods additional to database searching used to identify relevant reports? 2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? 2.4 Were restrictions based on date, publication format, or language appropriate? 2.5 Were efforts made to minimise error in selection of studies? Concerns regarding methods used to identify and/or select studies DOMAIN 3: DATA COLLECTION AND STUDY APPRAISAL Describe methods of data collection, what data were extracted from studies or collected through other means, how risk of bias was assessed (e.g. number of reviewers involved) and the tool used to assess risk of bias: 3.1 Were efforts made to minimise error in data collection? 3.2 Were sufficient study characteristics available for both review authors and readers to be able to interpret the results? 3.3 Were all relevant study results collected for use in the synthesis? 3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? 3.5 Were efforts made to minimise error in risk of bias assessment? Concerns regarding methods used to collect data and appraise studies

6 DOMAIN 4: SYNTHESIS AND FINDINGS Describe synthesis methods: 4.1 Did the synthesis include all studies that it should? 4.2 Were all pre-defined analyses reported or departures explained? 4.3 Was the synthesis appropriate given the nature and similarity in the research questions, study designs and outcomes across included studies? 4.4 Was between-study variation (heterogeneity) minimal or addressed in the synthesis? 4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? 4.6 Were biases in primary studies minimal or addressed in the synthesis? Concerns regarding the synthesis and findings Y=YES, PY=PROBABLY YES, PN=PROBABLY NO, N=NO, NI=NO INFORMATION Phase 3: Judging risk of bias Summarize the concerns identified during the Phase 2 assessment: Domain Concern Rationale for concern 1. Concerns regarding specification of study eligibility criteria 2. Concerns regarding methods used to identify and/or select studies 3. Concerns regarding methods used to collect data and appraise studies 4. Concerns regarding the synthesis and findings RISK OF BIAS IN THE REVIEW Describe whether conclusions were supported by the evidence: A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? B. Was the relevance of identified studies to the review's research question appropriately considered? C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Risk of bias in the review Rationale for risk: Y=YES, PY=PROBABLY YES, PN=PROBABLY NO, N=NO, NI=NO INFORMATION RISK:

7 ROBIS: Tool to assess risk of bias in systematic reviews Tafelski et al Phase 1: Assessing relevance (Optional) ROBIS is designed to assess the risk of bias in reviews with questions relating to interventions, aetiology, diagnosis and prognosis. State your overview/guideline question (target question) and the question being addressed in the review being assessed: Intervention reviews: Patients/Population(s): Intervention(s): Comparator(s): Outcome(s): For aetiology reviews: Patients/Population(s): Exposure(s) and comparator(s): Outcome(s): For DTA reviews: Patients): Index test(s): Reference standard: Target condition: For prognostic reviews: Patients: Outcome to be predicted: Intended use of model: Intended moment in time: Does the question addressed by the review match the target question? YES/NO/UNCLEAR

8 Phase 2: Identifying concerns with the review process DOMAIN 1: STUDY ELIGIBILITY CRITERIA Describe the study eligibility criteria, any restrictions on eligibility and whether there was evidence that objectives and eligibility criteria were pre-specified: 1.1 Did the review adhere to pre-defined objectives and eligibility criteria? 1.2 Were the eligibility criteria appropriate for the review question? 1.3 Were eligibility criteria unambiguous? 1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? 1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Concerns regarding specification of study eligibility criteria DOMAIN 2: IDENTIFICATION AND SELECTION OF STUDIES Describe methods of study identification and selection (e.g. number of reviewers involved): 2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? 2.2 Were methods additional to database searching used to identify relevant reports? 2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? 2.4 Were restrictions based on date, publication format, or language appropriate? 2.5 Were efforts made to minimise error in selection of studies? Concerns regarding methods used to identify and/or select studies no unpublished studies included DOMAIN 3: DATA COLLECTION AND STUDY APPRAISAL Describe methods of data collection, what data were extracted from studies or collected through other means, how risk of bias was assessed (e.g. number of reviewers involved) and the tool used to assess risk of bias: 3.1 Were efforts made to minimise error in data collection? 3.2 Were sufficient study characteristics available for both review authors and readers to be able to interpret the results? 3.3 Were all relevant study results collected for use in the synthesis? 3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? 3.5 Were efforts made to minimise error in risk of bias assessment? Concerns regarding methods used to collect data and appraise studies

9 DOMAIN 4: SYNTHESIS AND FINDINGS Describe synthesis methods: 4.1 Did the synthesis include all studies that it should? 4.2 Were all pre-defined analyses reported or departures explained? 4.3 Was the synthesis appropriate given the nature and similarity in the research questions, study designs and outcomes across included studies? 4.4 Was between-study variation (heterogeneity) minimal or addressed in the synthesis? 4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? 4.6 Were biases in primary studies minimal or addressed in the synthesis? Concerns regarding the synthesis and findings Y=YES, PY=PROBABLY YES, PN=PROBABLY NO, N=NO, NI=NO INFORMATION Phase 3: Judging risk of bias review of reviews, primary study results not considered Summarize the concerns identified during the Phase 2 assessment: Domain Concern Rationale for concern 1. Concerns regarding specification of study eligibility criteria 2. Concerns regarding methods used to no unpublished studies considered identify and/or select studies 3. Concerns regarding methods used to collect data and appraise studies 4. Concerns regarding the synthesis and primary study results not considered findings RISK OF BIAS IN THE REVIEW Describe whether conclusions were supported by the evidence: A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? B. Was the relevance of identified studies to the review's research question appropriately considered? C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Risk of bias in the review Rationale for risk: Y=YES, PY=PROBABLY YES, PN=PROBABLY NO, N=NO, NI=NO INFORMATION RISK:

10 ROBIS: Tool to assess risk of bias in systematic reviews Whiting et al Phase 1: Assessing relevance (Optional) ROBIS is designed to assess the risk of bias in reviews with questions relating to interventions, aetiology, diagnosis and prognosis. State your overview/guideline question (target question) and the question being addressed in the review being assessed: Intervention reviews: Patients/Population(s): Intervention(s): Comparator(s): Outcome(s): For aetiology reviews: Patients/Population(s): Exposure(s) and comparator(s): Outcome(s): For DTA reviews: Patients): Index test(s): Reference standard: Target condition: For prognostic reviews: Patients: Outcome to be predicted: Intended use of model: Intended moment in time: Does the question addressed by the review match the target question? YES/NO/UNCLEAR

11 Phase 2: Identifying concerns with the review process DOMAIN 1: STUDY ELIGIBILITY CRITERIA Describe the study eligibility criteria, any restrictions on eligibility and whether there was evidence that objectives and eligibility criteria were pre-specified: 1.1 Did the review adhere to pre-defined objectives and eligibility criteria? 1.2 Were the eligibility criteria appropriate for the review question? 1.3 Were eligibility criteria unambiguous? 1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? 1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Concerns regarding specification of study eligibility criteria DOMAIN 2: IDENTIFICATION AND SELECTION OF STUDIES Describe methods of study identification and selection (e.g. number of reviewers involved): 2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? 2.2 Were methods additional to database searching used to identify relevant reports? 2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? 2.4 Were restrictions based on date, publication format, or language appropriate? 2.5 Were efforts made to minimise error in selection of studies? Concerns regarding methods used to identify and/or select studies DOMAIN 3: DATA COLLECTION AND STUDY APPRAISAL Describe methods of data collection, what data were extracted from studies or collected through other means, how risk of bias was assessed (e.g. number of reviewers involved) and the tool used to assess risk of bias: 3.1 Were efforts made to minimise error in data collection? 3.2 Were sufficient study characteristics available for both review authors and readers to be able to interpret the results? 3.3 Were all relevant study results collected for use in the synthesis? 3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? 3.5 Were efforts made to minimise error in risk of bias assessment? Concerns regarding methods used to collect data and appraise studies

12 DOMAIN 4: SYNTHESIS AND FINDINGS Describe synthesis methods: 4.1 Did the synthesis include all studies that it should? 4.2 Were all pre-defined analyses reported or departures explained? 4.3 Was the synthesis appropriate given the nature and similarity in the research questions, study designs and outcomes across included studies? 4.4 Was between-study variation (heterogeneity) minimal or addressed in the synthesis? 4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? 4.6 Were biases in primary studies minimal or addressed in the synthesis? Concerns regarding the synthesis and findings Y=YES, PY=PROBABLY YES, PN=PROBABLY NO, N=NO, NI=NO INFORMATION Phase 3: Judging risk of bias Summarize the concerns identified during the Phase 2 assessment: Domain Concern Rationale for concern 1. Concerns regarding specification of study eligibility criteria 2. Concerns regarding methods used to identify and/or select studies 3. Concerns regarding methods used to collect data and appraise studies 4. Concerns regarding the synthesis and findings Nausea/ vomiting: Error in data selection and meta-analysis > enhanced risk of bias in judging adverse effects of Cannabis RISK OF BIAS IN THE REVIEW Describe whether conclusions were supported by the evidence: A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? B. Was the relevance of identified studies to the review's research question appropriately considered? C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Risk of bias in the review Rationale for risk: Y=YES, PY=PROBABLY YES, PN=PROBABLY NO, N=NO, NI=NO INFORMATION RISK: