Voskoboinik A, Kalman JM, De Silva A, et al. Alcohol Abstinence in Drinkers with Atrial Fibrillation. N Engl J Med. 2020;382(1):20–28. doi:10.1056/NEJMoa1817591
Was the assignment of patients to treatments randomized?
–Yes, patients were randomized by a computerized central randomization in a 1:1 ratio.
Were all the patients who entered the trial properly accounted for and attributed at its conclusion?
– Some patients were excluded or did not have some portions of data available at the conclusion of the trial. I felt as though this was accounted for in general though.
Was follow-up complete?
– I believe follow up was very impressive though not entirely complete. 137/140 patients completed a 6 month follow up with complete rhythm data and alcohol history available.
Were patients analyzed in the groups to which they were randomized?
– yes. There was no shifting of patients between the abstinence and control group based on actual volume of alcohol consumed.
Were patients, health workers, and study personnel blind to treatment?
–Patients were not blinded as they had to be informed in order to alter their alcohol consumption PRN. I did not see if health workers were explicitly blinded however study personnel performing statistical analysis were blinded.
Were the groups similar at the start of the trial?
–Yes, per table 1
Aside from experimental intervention, were the groups treated equally?
– Yes, there was no treatment administered outside the experimental “treatment”.
| 1a | Identification as a randomized trial in the title | No | |
| 1b | Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts) | yes | |
| Introduction | |||
| Background and objectives | 2a | Scientific background and explanation of rationale | Not really |
| 2b | Specific objectives or hypotheses | Again, not very specific | |
| Methods | |||
| Trial design | 3a | Description of trial design (such as parallel, factorial) including allocation ratio | yes |
| 3b | Important changes to methods after trial commencement (such as eligibility criteria), with reasons | Yes, shortened from 12 months to 6 months | |
| Participants | 4a | Eligibility criteria for participants | yes |
| 4b | Settings and locations where the data were collected | yes | |
| Interventions | 5 | The interventions for each group with sufficient details to allow replication, including how and when they were actually administered | yes |
| Outcomes | 6a | Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed | yes |
| 6b | Any changes to trial outcomes after the trial commenced, with reasons | n | |
| Sample size | 7a | How sample size was determined | n |
| 7b | When applicable, explanation of any interim analyses and stopping guidelines | n | |
| Randomisation: | |||
| Sequence generation | 8a | Method used to generate the random allocation sequence | online |
| 8b | Type of randomisation; details of any restriction (such as blocking and block size) | – | |
| Allocation concealment mechanism | 9 | Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned | – |
| Implementation | 10 | Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions | – |
| Blinding | 11a | If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how | Cardiologists were blinded if interpreting ECGs |
| 11b | If relevant, description of the similarity of interventions | – | |
| Statistical methods | 12a | Statistical methods used to compare groups for primary and secondary outcomes | yea |
| 12b | Methods for additional analyses, such as subgroup analyses and adjusted analyses | yes | |
| Results | |||
| Participant flow (a diagram is strongly recommended) | 13a | For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome | yes |
| 13b | For each group, losses and exclusions after randomisation, together with reasons | yes | |
| Recruitment | 14a | Dates defining the periods of recruitment and follow-up | yes |
| 14b | Why the trial ended or was stopped | yes | |
| Baseline data | 15 | A table showing baseline demographic and clinical characteristics for each group | yes |
| Numbers analysed | 16 | For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups | yes |
| Outcomes and estimation | 17a | For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) | yes |
| 17b | For binary outcomes, presentation of both absolute and relative effect sizes is recommended | – | |
| Ancillary analyses | 18 | Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory | yes |
| Harms | 19 | All important harms or unintended effects in each group (for specific guidance see CONSORT for harms) | – |
| Discussion | |||
| Limitations | 20 | Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses | yes |
| Generalisability | 21 | Generalisability (external validity, applicability) of the trial findings | – |
| Interpretation | 22 | Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence | yes |
| Other information | |||
| Registration | 23 | Registration number and name of trial registry | – |
| Protocol | 24 | Where the full trial protocol can be accessed, if available | yes |
| Funding | 25 | Sources of funding and other support (such as supply of drugs), role of funders | yes |
Critical appraisal:
I believe this study is methodologically sound. There are no major flaws within the study design itself. There were relatively significant portions of data missing pertaining to secondary endpoints, which was acknowledged by the authors.
Compare and contrast User’s with CONSORT:
Though User’s Guide continues to be my preferred manner of article appraisal, the CONSORT checklist did provide me with reassurance of the validity of the trial that I don’t think I would have reached with User’s Guide alone. Going forward I will definitely use User’s Guide but may employ CONSORT when evaluating therapy studies that I find difficult to interpret or adequately evaluate their design validity.
Math:
What is the outcome you want to use and what is the baseline risk of the outcome for patients in the study? (It’s the event rate of control group in the study. Need to know risk of the outcome without any treatment.)
-My outcome is freedom of recurrence of atrial fibrillation in “Adults (without alcohol use disorder) who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline.” Event rate of the control group (no intervention) was 73% had an AF recurrence recorded by 6 months.
What is the RRR and the NNT for this outcome from the study?
-The RRR in the abstinence group was 27.4%
-ARR between the control (73%) and abstinence group (53%) was 20%
-NNT was 5. 1/(0.2) = 5
Using those as a baseline, calculate the following patient-specific NNTs:
- F method: A patient who is 5 times more likely to develop the outcome?
- 5/5 = 1
- F method: A patient who is 75% less likely to develop the outcome? (hint: f will be 0.25)
- 5/0.25 = 20
- PEER method: A patient whose baseline risk (or expected event rate) is 10%?
- 1/(0.1)(0.274) = 36.50
- PEER method: A patient whose baseline risk is 60%?
- 1/(0.6)(0.274) = 6.08
Evidence Blaked Medicine 