Study Note
This study examined the effect of high-dose vitamin D3 before tumor surgery on the subjective perception of pain and the use of painkillers after surgery in 60 patients with brain tumors and low vitamin D levels. Three days after the operation, there were no significant differences between patients who had been injected with 300,000 IU 2-14 days before the operation and the control patients in terms of subjective pain perception and painkiller use. Numerous criticisms can be made of this study, e.g. significant differences between the intervention and control arms at the start of the study, inadequate descriptions of the interventions in the intervention and control arms, and unclear calculations.
Diese Studie untersuchte bei 60 Patienten mit Gehirntumoren und zu niedrigem Vitamin D Spiegel die Wirkung von hochdosiertem Vitamin D3 vor der Tumoroperation auf die subjektive Schmerzwahrnehmung und den Schmerzmittelgebrauch nach der Operation. Jeweils 3 Tage nach der Operation zeigten sich zwischen Patienten, die 2-14 Tage vor der Operation 300,000 IU injiziert bekamen und den Kontrollpatienten keine bedeutsamen Unterschiede hinsichtlich subjektiver Schmerzwahrnehmung und Schmerzmittelgebrauch. An dieser Studie lassen sich zahlreiche Kritikpunkte nennen, z.B. bedeutsame Unterschiede zwischen Interventions- und Kontrollarm zum Beginn der Studie, unzureichende Beschreibungen der Interventionen in Interventions- und Kontrollarm, sowie unklare Berechnungen.
Brief summary
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
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| Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals
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| 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
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| Is randomized
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Yes
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| Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control
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No
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| Number of arms
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-999
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Study characteristics
| Inclusion criteria
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| Exclusion criteria
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| N randomized
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-999
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| 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.
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| Specifications on analyses
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| Countries of data collection
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| LoE Level of evidence
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| Outcome timeline Data collection times
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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.
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| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included
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| 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
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| Specifications on cancer stages
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| Comorbidities
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| Current cancer therapies
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| Specifications on cancer therapies
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| Previous cancer therapies
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| Gender
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| Gender specifications
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| Age groups
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| Age groups specification
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Arms
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Intervention
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| Number of participants (arm) N randomized
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35
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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5
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| Drop-out reasons
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Missed follow-up
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| Intervention
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Vitamin D
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| Dosage and regime
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Intramuscular injection of 300,000 IU vitamin D 2-14 days (with an average of 5 days) before surgery
+ all participants: pain medication, including intravenous injection of apotel 1 g, morphine sulfate 3 mg, and oral acet-aminophen 500 mg, depending on each patient’s need in the intensive care unit and ward
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| One-time application
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No
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| 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.
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-999
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| Side effects / Interactions
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NI
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| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Passive control
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| Number of participants (arm) N randomized
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36
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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6
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| Drop-out reasons
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Missed follow-up
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| Intervention
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Nothing
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| Dosage and regime
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All participants: pain medication, including intravenous injection of apotel 1 g, morphine sulfate 3 mg, and oral acet-aminophen 500 mg, depending on each patient’s need in the intensive care unit and ward
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| One-time application
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No
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| 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.
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-999
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| Side effects / Interactions
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NI
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Outcomes
Pain
| Outcome type As specificed by the authors
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NI
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| Outcome specification
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Postoperative pain (doses of analgesic medication consumption)
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| Type of measurement
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VAS (Visual Analogue Scale), Observation
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| 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".
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No significant differences in VAS scores;
No significant differences in doses of analgesic medication consumption
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| 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".
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NI
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
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some concerns
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| Bias due to deviation from intended intervention (assignment to intervention)
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high risk
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
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low risk
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| Bias in measurement of the outcome
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some concerns
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| Bias in selection of the reported result
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low risk
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| Other sources of bias
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NA
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| Overall RoB judgment
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high risk
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Vitamin D level
| Outcome type As specificed by the authors
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Others
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| Outcome specification
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NA
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| Type of measurement
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Blood Test
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| 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".
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Increase in 25(OH) D on the fifth postoperative day in intervention arm was statistically significant compared with the control arm (p = 0.001)
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| 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".
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NI
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
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NA
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| Bias due to deviation from intended intervention (assignment to intervention)
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NA
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
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NA
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| Bias in measurement of the outcome
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NA
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| Bias in selection of the reported result
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NA
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| Other sources of bias
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NA
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| Overall RoB judgment
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NA
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Funding and Conflicts of Interest
| Funding
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| Conflicts of Interest
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Further points for assessing the study
Sample
| Power analysis performed
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| - Sample size corresponds to power analysis
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| - Reasons for insufficient sample size based on power analysis
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| If no power analysis performed: at least moderate sample size (n >= 30 per arm)
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| Ethnicity mentioned
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Alternative Explanation
| Other explanations for an effect besides the investigated intervention
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| - Possibility of attention effects
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| - Possibility of placebo effects
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| - Other reasons
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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
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| Correction for multiple testing
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| Measurement of compliance
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| Consistent reporting in numbers (figures, flowchart, abstract, results)
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| Comprehensive and coherent reporting
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| Cross-over
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| - Sufficient washout period
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| - Tested for carry-over effects
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| - Tested for sequence effects
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Interpretation of results
| Effect sizes reported (clinical vs. statistical significance)
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| Side effects systematically recorded
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| Side effects considered in result interpretation
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| Ethics votum
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Additional Notes
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