Côté et al. (2016): Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial: Difference between revisions
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|Reference=Publication: Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial | |Reference=Publication: Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial | ||
}} | }} | ||
=Brief summary= | =Brief summary= | ||
In the study, 56 patients with head and neck tumors were randomly divided into | In the study, 56 patients with head and neck tumors were randomly divided into two arms, one received nabilone (synthetic THC) every day and the other a placebo. All patients received radiotherapy or a combination of radiotherapy and chemotherapy for seven weeks. At the end of the study, the authors found no differences between the arms for quality of life in general, as well as the symptoms of pain, weight fluctuations, appetite, nausea, mood and sleep. The study sample was small and 24 patients dropped out over the course of the study. The presentation of the results is superficial and inadequate. Without statistical values (mean values), the analysis is not transparent. Further methodological deficiencies in the analysis do not allow any conclusions to be drawn about the results. | ||
In der Studie wurden 56 Patienten mit Kopf-Hals Tumoren zufällig in | In der Studie wurden 56 Patienten mit Kopf-Hals Tumoren zufällig in zwei Gruppen eingeteilt, wovon eine Gruppe jeden Tag Nabilon (synthetisches THC) bekam und die andere ein Placebo. Alle Patienten bekamen für sieben Wochen Radiotherapie oder eine Kombination aus Radio- und Chemotherapie. Am Ende der Studie fanden die Autoren keine Unterschiede zwischen den Gruppen für Lebensqualität allgemein, als auch für die Symptome Schmerz, Gewichtsschwankungen, Appetit, Übelkeit, Stimmung und Schlaf. Die Stichprobe der Studie war klein und es sind über den Verlauf der Studie noch 24 Patienten ausgestiegen. Die Darstellung der Ergebnisse ist oberflächlich und unzureichend. Ohne Angabe von statistischen Werten (Mittelwerte) ist eine Transparenz der Analyse nicht gegeben. Weitere methodische Mängel in der Analyse lassen keine Aussagen zu den Ergebnissen zu. | ||
=Study Design= | =Study Design= | ||
| Line 26: | Line 24: | ||
|Exclusion criteria=Metastatic disease; history of radiotherapy in the head and neck region; Karnofsky score <60; cognitive impairment; hepatic insufficiency; pregnant or breastfeeding woman; history of hypersensitivity or adverse reactions to marijuana or other cannabinoids; history of schizophrenia or any other form of psychosis | |Exclusion criteria=Metastatic disease; history of radiotherapy in the head and neck region; Karnofsky score <60; cognitive impairment; hepatic insufficiency; pregnant or breastfeeding woman; history of hypersensitivity or adverse reactions to marijuana or other cannabinoids; history of schizophrenia or any other form of psychosis | ||
|N randomized=56 | |N randomized=56 | ||
|Analysis= | |Analysis=PP Analysis | ||
|Specifications on analyses=Repeated measures analyses of variance (ANOVA), estimated with a linear mixed model, enable us to test the effect of time and treatment on continuous outcomes, while a generalized linear mixed model is used as a logistic regression for dichotomous outcomes. The P values that are presented are for the interaction term of these models. All the analyses were also carried out while adjusting for site, treatment, and tumor size. | |Specifications on analyses=Repeated measures analyses of variance (ANOVA), estimated with a linear mixed model, enable us to test the effect of time and treatment on continuous outcomes, while a generalized linear mixed model is used as a logistic regression for dichotomous outcomes. The P-values that are presented are for the interaction term of these models. All the analyses were also carried out while adjusting for site, treatment, and tumor size. | ||
|Countries of data collection=Canada | |Countries of data collection=Canada | ||
|LoE=Level 2 Oxford 2011 | |LoE=Level 2 Oxford 2011 | ||
|Outcome timeline=T0: baseline | |Outcome timeline=T0: baseline before radiotherapy | ||
T1: | |||
T2: | T1: first week | ||
T2: second week until | |||
T3: 7<sup>th</sup> week | |||
Follow-up: between 9<sup>th</sup> - 11<sup>th</sup> week | |||
}} | }} | ||
=Characteristics of participants= | =Characteristics of participants= | ||
{{Characteristics of participants | {{Characteristics of participants | ||
|Setting=Neo-adjuvant, Adjuvant | |Setting=Curative, Neo-adjuvant, Adjuvant | ||
|Types of cancer=Head and Neck Cancers | |Types of cancer=Head and Neck Cancers | ||
|Stage cancer=NI | |Stage cancer=NI | ||
|Cancer stage specification=NI | |Cancer stage specification=NI | ||
|Comorbidity=NI | |Comorbidity=NI | ||
|Current cancer therapy=Radiation therapy | |Current cancer therapy=Chemotherapy, Radiation therapy | ||
|Specifications on cancer therapies=Radiotherapy only: intervention | |Specifications on cancer therapies=Radiotherapy only: | ||
Radiotherapy postoperative: intervention | |||
Radiochemotherapy: intervention | intervention arm = 13; placebo arm = 10 | ||
Radiochemotherapy postoperative: intervention | |||
Radiotherapy postoperative: | |||
intervention arm = 7; placebo arm = 2 | |||
Radiochemotherapy: | |||
intervention arm = 7; placebo arm = 15 | |||
Radiochemotherapy postoperative: | |||
intervention arm = 1, placebo arm = 1 | |||
|Previous cancer therapies=Surgery, No therapy | |Previous cancer therapies=Surgery, No therapy | ||
|Gender=Mixed | |Gender=Mixed | ||
|Gender specifications=Female n | |Gender specifications=Female n = 10 (17.86%); male n = 46 (82.14%) | ||
|Age groups=Adults (18+) | |Age groups=Adults (18+) | ||
|Age groups specification= | |Age groups specification=Mean age per arm: | ||
intervention | |||
intervention arm = 63.5 years | |||
placebo arm = 63.8 years | |||
}} | }} | ||
=Arms= | =Arms= | ||
| Line 63: | Line 78: | ||
|Number of participants (arm)=28 | |Number of participants (arm)=28 | ||
|Drop-out=9 | |Drop-out=9 | ||
|Drop-out reasons= | |Drop-out reasons=Not arm specified: severe nausea (n = 5); difficulty swallowing (n = 4); hospitalization (n = 4), pneumonia (n = 1); discontinued RT (n = 1); without reason (n = 9) | ||
|Intervention=Nabilon | |Intervention=Nabilon | ||
+ | |||
|Dosage and regime=0.5 mg nabilone tablets | |||
+ all patients: additional administration of antiemetics (metoclopramide) and painkillers (acetaminophen (paracetamol), codeine, hydromorphone or transdermal fentanyl) possible | |||
|Dosage and regime=0.5 mg nabilone tablets (from Valeant Canada) | |||
* once a day before radiotherapy in the first week | |||
* twice a day in the second week | |||
* third week until end of radiotherapy: adjusted by radiation oncologist up to maximal 4 tablets | |||
|One-time application=No | |One-time application=No | ||
|Duration in days= | |Duration in days=49 | ||
|Side Effects / Interactions=No differences for sleepiness (p=0. | |Side Effects / Interactions=No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83) | ||
|Order number=1 | |Order number=1 | ||
|Arm topic=Cannabinoids | |||
}} | }} | ||
{{Arm | {{Arm | ||
| Line 78: | Line 97: | ||
|Number of participants (arm)=28 | |Number of participants (arm)=28 | ||
|Drop-out=15 | |Drop-out=15 | ||
|Drop-out reasons= | |Drop-out reasons=Not arm specified: severe nausea (n = 5); difficulty swallowing (n = 4); hospitalization (n = 4), pneumonia (n = 1); discontinued RT (n = 1); without reason (n = 9) | ||
|Intervention=Placebo | |Intervention=Placebo | ||
+ | |||
|Dosage and regime= | |||
+ all patients: additional administration of antiemetics (metoclopramide) and painkillers (acetaminophen (paracetamol), codeine, hydromorphone or transdermal fentanyl) possible | |||
|Dosage and regime=Placebo tablets | |||
* once a day before radiotherapy in the first week | |||
* twice a day in the second week | |||
* third week until end of radiotherapy: adjusted by radiation oncologist up to maximal 4 tablets | |||
|One-time application=No | |One-time application=No | ||
|Duration in days= | |Duration in days=49 | ||
|Side Effects / Interactions=No differences for sleepiness (p=0. | |Side Effects / Interactions=No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83) | ||
|Order number=2 | |Order number=2 | ||
|Arm topic=Cannabinoids | |||
}} | }} | ||
{{Arm Overview}} | {{Arm Overview}} | ||
| Line 96: | Line 120: | ||
|Outcome specification=Quality of life (target improvement of 15 points at week 7) | |Outcome specification=Quality of life (target improvement of 15 points at week 7) | ||
|Type of measurement=EORTC QLQ (European Organisation for Research and Treatment of Cancer Core/ Quality of Life questionnaire) | |Type of measurement=EORTC QLQ (European Organisation for Research and Treatment of Cancer Core/ Quality of Life questionnaire) | ||
|Results during intervention= | |Results during intervention=No difference between arms (p=0.4270), even after controlling for tumor site, treatment method and cancer stage at week 7 or the entire study period | ||
|Results after intervention=No | |Results after intervention=No difference between arms (p=0.4270), even after controlling for tumor site, treatment method and cancer stage at week 7 or the entire study period | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=some concerns | ||
|Other sources of bias= | |Other sources of bias=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=1 | |Order number=1 | ||
|Outcome topic=Cannabinoids | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 112: | Line 137: | ||
|Outcome name=Pain | |Outcome name=Pain | ||
|Outcome specification=Pain with VAS + number of other analgesics used | |Outcome specification=Pain with VAS + number of other analgesics used | ||
|Type of measurement=VAS (Visual Analogue Scale), | |Type of measurement=VAS (Visual Analogue Scale), Observation | ||
|Results during intervention= | |Results during intervention=Over the course of the intervention and after: no differences for pain (p=0.6048), analgesic use (p=0.6671), no delay in time to 20% pain increase (p=0.4614) between arms | ||
|Results after intervention= | |Results after intervention=Over the course of the intervention and after: no differences for pain (p=0.6048), analgesic use (p=0.6671), no delay in time to 20% pain increase (p=0.4614) between arms | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=some concerns | ||
|Other sources of bias= | |Other sources of bias=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=2 | |Order number=2 | ||
|Outcome topic=Cannabinoids | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 130: | Line 156: | ||
|Outcome specification=Weight fluctuations, total days without feeding tube or gastrostomy | |Outcome specification=Weight fluctuations, total days without feeding tube or gastrostomy | ||
|Type of measurement=Scale | |Type of measurement=Scale | ||
|Results during intervention= | |Results during intervention=Over the course of the intervention and after: no difference for weight fluctuations (p=0.1454) or need for a feeding tube (no p-value) between arms. | ||
|Results after intervention= | |Results after intervention=Over the course of the intervention and after: no difference for weight fluctuations (p=0.1454) or need for a feeding tube (no p-value) between arms. | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=some concerns | ||
|Other sources of bias= | |Other sources of bias=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=3 | |Order number=3 | ||
|Outcome topic=Cannabinoids | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 146: | Line 173: | ||
|Outcome name=Appetite | |Outcome name=Appetite | ||
|Outcome specification=Appetite with questionnaire (no further information) | |Outcome specification=Appetite with questionnaire (no further information) | ||
|Type of measurement= | |Type of measurement=Unspecified questionnaire | ||
|Results during intervention= | |Results during intervention=Over the course of the intervention and after: no difference (p=0.3295) between arms | ||
|Results after intervention= | |Results after intervention=Over the course of the intervention and after: no difference (p=0.3295) between arms | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=some concerns | ||
|Other sources of bias= | |Other sources of bias=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=4 | |Order number=4 | ||
|Outcome topic=Cannabinoids | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 163: | Line 191: | ||
|Outcome name=Nausea | |Outcome name=Nausea | ||
|Outcome specification=Nausea with questionnaire (no further information) + number of antiemetic drugs used | |Outcome specification=Nausea with questionnaire (no further information) + number of antiemetic drugs used | ||
|Type of measurement= | |Type of measurement=Unspecified questionnaire | ||
|Results during intervention= | |Results during intervention=Over the course of the intervention and after: no difference for nausea (p=0.7105) or antiemetic consumption (p=0.6124) between arms | ||
|Results after intervention= | |Results after intervention=Over the course of the intervention and after: no difference for nausea (p=0.7105) or antiemetic consumption (p=0.6124) between arms | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=some concerns | ||
|Other sources of bias= | |Other sources of bias=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=5 | |Order number=5 | ||
|Outcome topic=Cannabinoids | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
|Outcome type=Secondary | |Outcome type=Secondary | ||
|Outcome name=Unspecified effects | |Outcome name=Unspecified effects | ||
|Outcome specification=Sleep quality | |Outcome specification=Sleep quality and mood (no information on survey) | ||
|Type of measurement=NI | |Type of measurement=NI | ||
|Results during intervention= | |Results during intervention=Over the course of the intervention and after: no differences for mood (p=0.3214) and sleep quality (p=0.4438) between arms | ||
|Results after intervention= | |Results after intervention=Over the course of the intervention and after: no differences for mood (p=0.3214) and sleep quality (p=0.4438) between arms | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=some concerns | ||
|Other sources of bias= | |Other sources of bias=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=6 | |Order number=6 | ||
|Outcome topic=Cannabinoids | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 197: | Line 227: | ||
|Outcome name=Toxicity | |Outcome name=Toxicity | ||
|Outcome specification=Toxicity of nabilone | |Outcome specification=Toxicity of nabilone | ||
|Type of measurement= | |Type of measurement=NI | ||
|Results during | |Results during intervention=No differences for sleepiness (p=0.3166), anxiety (p=0.9163) and xerostomia (p=0.8341) | ||
|Results after intervention=NA | |||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=some concerns | ||
|Other sources of bias= | |Other sources of bias=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=7 | |Order number=7 | ||
|Outcome topic=Cannabinoids | |||
}} | }} | ||
{{Outcome Overview}} | {{Outcome Overview}} | ||
| Line 215: | Line 246: | ||
{{Funding and Conflicts of Interest | {{Funding and Conflicts of Interest | ||
|Funding=The authors received research grants from the Canadian Institutes of Health Research and the Fonds de recherche en santé du Québec. ICN Valeant Pharmaceuticals provided the nabilone and the placebo pills during the trial. | |Funding=The authors received research grants from the Canadian Institutes of Health Research and the Fonds de recherche en santé du Québec. ICN Valeant Pharmaceuticals provided the nabilone and the placebo pills during the trial. | ||
|Conflicts of Interest=According to authors no conflict of interest | |Conflicts of Interest=According to authors no conflict of interest. | ||
}} | }} | ||
=Further points for assessing the study= | =Further points for assessing the study= | ||
{{Further points for assessing the study | {{Further points for assessing the study | ||
|Samples sufficiently large= | |power analysis performed=Yes | ||
| | |Sample size corresponds to power analysis=Yes | ||
|Reasons given for samples being too small according to power analysis=NA | |||
|Samples sufficiently large=NA | |||
|Ethnicity mentioned=No | |||
|Other explanations for an effect besides the investigated intervention=No | |||
|Possibility of attention effects=NA | |||
|Possibility of placebo effects=NA | |||
|Other reasons=NA | |||
|Correct use of parametric and non-parametric tests=NI | |||
|Correction for multiple testing=No | |||
|Measurement of compliance=NI | |||
|Consistent reporting in numbers=Yes | |||
|Comprehensive and coherent reporting=No | |||
|Cross-over=No | |||
|sufficient washout period=NA | |||
|Tested for carry-over effects=NA | |||
|Were sequence effects tested=NA | |||
|Effect sizes reported=No | |||
|Were side effects systematically recorded=Yes | |||
|Side effects taken into account in the interpretation of the results=Yes | |||
|Ethics / CoI / Funding=Yes | |||
|Blinding reliable=Yes | |||
|Check whether blinding was successful=No | |||
|reasons given for samples being too small according to power analysis=? | |reasons given for samples being too small according to power analysis=? | ||
|Testing for normal distribution=? | |Testing for normal distribution=? | ||
|Correct application of statistical tests=? | |Correct application of statistical tests=? | ||
|mono- or multicentric=? | |mono- or multicentric=? | ||
}} | }} | ||
{{Additional Notes | {{Additional Notes | ||
|Additional Notes=PRO: | |||
* Ethical approval | |||
* Power analysis | |||
* Intent-to-treat analysis | |||
* Baseline comparability | |||
* Mention of drop-out comparison in the discussion, though no statistical values are provided | |||
CONTRA: | |||
* Lack of blinding control | |||
* No correction for multiple testing | |||
* Superficial and inadequate presentation of results: results are only shown graphically, with no mean/SD values available, lacking transparency | |||
* Very high drop-out rate, with 12 out of 15 participants in placebo arm who dropped out receiving Radiochemotherapy | |||
* Exact dosing from week 3 onward may vary for each participant | |||
* Apart from the primary endpoint, no specific timing provided for final comparisons | |||
}} | |||
Latest revision as of 16:58, 26 November 2024
| Reference ↗ | |
|---|---|
| Title | Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial |
| Topic | Cannabinoids |
| Author | Côté, M, Trudel, M, Wang, C, Fortin, A |
| Year | 2016 |
| Journal | Annals of Otology, Rhinology & Laryngology |
| DOI | https://doi.org/10.1177/0003489415612801 |
Brief summary
In the study, 56 patients with head and neck tumors were randomly divided into two arms, one received nabilone (synthetic THC) every day and the other a placebo. All patients received radiotherapy or a combination of radiotherapy and chemotherapy for seven weeks. At the end of the study, the authors found no differences between the arms for quality of life in general, as well as the symptoms of pain, weight fluctuations, appetite, nausea, mood and sleep. The study sample was small and 24 patients dropped out over the course of the study. The presentation of the results is superficial and inadequate. Without statistical values (mean values), the analysis is not transparent. Further methodological deficiencies in the analysis do not allow any conclusions to be drawn about the results.
In der Studie wurden 56 Patienten mit Kopf-Hals Tumoren zufällig in zwei Gruppen eingeteilt, wovon eine Gruppe jeden Tag Nabilon (synthetisches THC) bekam und die andere ein Placebo. Alle Patienten bekamen für sieben Wochen Radiotherapie oder eine Kombination aus Radio- und Chemotherapie. Am Ende der Studie fanden die Autoren keine Unterschiede zwischen den Gruppen für Lebensqualität allgemein, als auch für die Symptome Schmerz, Gewichtsschwankungen, Appetit, Übelkeit, Stimmung und Schlaf. Die Stichprobe der Studie war klein und es sind über den Verlauf der Studie noch 24 Patienten ausgestiegen. Die Darstellung der Ergebnisse ist oberflächlich und unzureichend. Ohne Angabe von statistischen Werten (Mittelwerte) ist eine Transparenz der Analyse nicht gegeben. Weitere methodische Mängel in der Analyse lassen keine Aussagen zu den Ergebnissen zu.
Study Design
| Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies | Prospective |
|---|---|
| Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals | Monocentric |
| Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties | Double |
| Is randomized | Yes |
| Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control | No |
| Number of arms | 2 |
Study characteristics
| Inclusion criteria | Histological diagnosis of squamous cell carcinoma of the oral cavity, the oropharynx, the hypopharynx, and/or the larynx; treated by radiotherapy alone, postoperative radiotherapy, radiochemotherapy alone, or postoperative radiochemotherapy; aged 18 to 80 years; no other cancer diagnosis in the past 5 years, except for basal cell and squamous cell carcinoma of the skin |
|---|---|
| Exclusion criteria | Metastatic disease; history of radiotherapy in the head and neck region; Karnofsky score <60; cognitive impairment; hepatic insufficiency; pregnant or breastfeeding woman; history of hypersensitivity or adverse reactions to marijuana or other cannabinoids; history of schizophrenia or any other form of psychosis |
| N randomized | 56 |
| Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment. | PP Analysis |
| Specifications on analyses | Repeated measures analyses of variance (ANOVA), estimated with a linear mixed model, enable us to test the effect of time and treatment on continuous outcomes, while a generalized linear mixed model is used as a logistic regression for dichotomous outcomes. The P-values that are presented are for the interaction term of these models. All the analyses were also carried out while adjusting for site, treatment, and tumor size. |
| Countries of data collection | Canada |
| LoE Level of evidence | Level 2 Oxford 2011 |
| Outcome timeline Data collection times | T0: baseline before radiotherapy
T1: first week T2: second week until T3: 7th week Follow-up: between 9th - 11th week |
Characteristics of participants
| Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors. | Curative, Neo-adjuvant, Adjuvant |
|---|---|
| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included | Head and Neck Cancers |
| Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis | NI |
| Specifications on cancer stages | NI |
| Comorbidities | NI |
| Current cancer therapies | Chemotherapy, Radiation therapy |
| Specifications on cancer therapies | Radiotherapy only:
intervention arm = 13; placebo arm = 10 Radiotherapy postoperative: intervention arm = 7; placebo arm = 2 Radiochemotherapy: intervention arm = 7; placebo arm = 15 Radiochemotherapy postoperative: intervention arm = 1, placebo arm = 1 |
| Previous cancer therapies | Surgery, No therapy |
| Gender | Mixed |
| Gender specifications | Female n = 10 (17.86%); male n = 46 (82.14%) |
| Age groups | Adults (18+) |
| Age groups specification | Mean age per arm:
intervention arm = 63.5 years placebo arm = 63.8 years |
Arms
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment | Intervention |
|---|---|
| Number of participants (arm) N randomized | 28 |
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date | 9 |
| Drop-out reasons | Not arm specified: severe nausea (n = 5); difficulty swallowing (n = 4); hospitalization (n = 4), pneumonia (n = 1); discontinued RT (n = 1); without reason (n = 9) |
| Intervention | Nabilon
|
| Dosage and regime | 0.5 mg nabilone tablets (from Valeant Canada)
|
| One-time application | No |
| Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information. | 49 |
| Side effects / Interactions | No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83) |
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment | Placebo |
|---|---|
| Number of participants (arm) N randomized | 28 |
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date | 15 |
| Drop-out reasons | Not arm specified: severe nausea (n = 5); difficulty swallowing (n = 4); hospitalization (n = 4), pneumonia (n = 1); discontinued RT (n = 1); without reason (n = 9) |
| Intervention | Placebo
|
| Dosage and regime | Placebo tablets
|
| One-time application | No |
| Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information. | 49 |
| Side effects / Interactions | No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83) |
Outcomes
Quality of life
| Outcome type As specificed by the authors | Primary |
|---|---|
| Outcome specification | Quality of life (target improvement of 15 points at week 7) |
| Type of measurement | EORTC QLQ (European Organisation for Research and Treatment of Cancer Core/ Quality of Life questionnaire) |
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | No difference between arms (p=0.4270), even after controlling for tumor site, treatment method and cancer stage at week 7 or the entire study period |
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | No difference between arms (p=0.4270), even after controlling for tumor site, treatment method and cancer stage at week 7 or the entire study period |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | some concerns |
| Other sources of bias | NA |
| Overall RoB judgment | some concerns |
Pain
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Pain with VAS + number of other analgesics used |
| Type of measurement | VAS (Visual Analogue Scale), Observation |
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no differences for pain (p=0.6048), analgesic use (p=0.6671), no delay in time to 20% pain increase (p=0.4614) between arms |
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no differences for pain (p=0.6048), analgesic use (p=0.6671), no delay in time to 20% pain increase (p=0.4614) between arms |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | some concerns |
| Other sources of bias | NA |
| Overall RoB judgment | some concerns |
Weight
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Weight fluctuations, total days without feeding tube or gastrostomy |
| Type of measurement | Scale |
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no difference for weight fluctuations (p=0.1454) or need for a feeding tube (no p-value) between arms. |
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no difference for weight fluctuations (p=0.1454) or need for a feeding tube (no p-value) between arms. |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | some concerns |
| Other sources of bias | NA |
| Overall RoB judgment | some concerns |
Appetite
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Appetite with questionnaire (no further information) |
| Type of measurement | Unspecified questionnaire |
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no difference (p=0.3295) between arms |
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no difference (p=0.3295) between arms |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | some concerns |
| Other sources of bias | NA |
| Overall RoB judgment | some concerns |
Nausea
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Nausea with questionnaire (no further information) + number of antiemetic drugs used |
| Type of measurement | Unspecified questionnaire |
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no difference for nausea (p=0.7105) or antiemetic consumption (p=0.6124) between arms |
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no difference for nausea (p=0.7105) or antiemetic consumption (p=0.6124) between arms |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | some concerns |
| Other sources of bias | NA |
| Overall RoB judgment | some concerns |
Unspecified effects
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Sleep quality and mood (no information on survey) |
| Type of measurement | NI |
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no differences for mood (p=0.3214) and sleep quality (p=0.4438) between arms |
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | Over the course of the intervention and after: no differences for mood (p=0.3214) and sleep quality (p=0.4438) between arms |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | some concerns |
| Other sources of bias | NA |
| Overall RoB judgment | some concerns |
Toxicity
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Toxicity of nabilone |
| Type of measurement | NI |
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | No differences for sleepiness (p=0.3166), anxiety (p=0.9163) and xerostomia (p=0.8341) |
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". | NA |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | some concerns |
| Other sources of bias | NA |
| Overall RoB judgment | some concerns |
Funding and Conflicts of Interest
| Funding | The authors received research grants from the Canadian Institutes of Health Research and the Fonds de recherche en santé du Québec. ICN Valeant Pharmaceuticals provided the nabilone and the placebo pills during the trial. |
|---|---|
| Conflicts of Interest | According to authors no conflict of interest. |
Further points for assessing the study
Sample
| Power analysis performed | Yes |
|---|---|
| - Sample size corresponds to power analysis | Yes |
| - Reasons for insufficient sample size based on power analysis | NA |
| If no power analysis performed: at least moderate sample size (n >= 30 per arm) | NA |
| Ethnicity mentioned | No |
Alternative Explanation
| Other explanations for an effect besides the investigated intervention | No |
|---|---|
| - Possibility of attention effects | NA |
| - Possibility of placebo effects | NA |
| - Other reasons | NA |
Statistics
| Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing | NI |
|---|---|
| Correction for multiple testing | No |
| Measurement of compliance | NI |
| Consistent reporting in numbers (figures, flowchart, abstract, results) | Yes |
| Comprehensive and coherent reporting | No |
| Cross-over | No |
| - Sufficient washout period | NA |
| - Tested for carry-over effects | NA |
| - Tested for sequence effects | NA |
Interpretation of results
| Effect sizes reported (clinical vs. statistical significance) | No |
|---|---|
| Side effects systematically recorded | Yes |
| Side effects considered in result interpretation | Yes |
| Ethics votum | Yes |
Additional Notes
PRO:
- Ethical approval
- Power analysis
- Intent-to-treat analysis
- Baseline comparability
- Mention of drop-out comparison in the discussion, though no statistical values are provided
CONTRA:
- Lack of blinding control
- No correction for multiple testing
- Superficial and inadequate presentation of results: results are only shown graphically, with no mean/SD values available, lacking transparency
- Very high drop-out rate, with 12 out of 15 participants in placebo arm who dropped out receiving Radiochemotherapy
- Exact dosing from week 3 onward may vary for each participant
- Apart from the primary endpoint, no specific timing provided for final comparisons