TANDEM TRIAL: A factorial randomized controlled trial of dose and review schedule of bevacizumab (Avastin) for neovascular macular degeneration in the East Midlands
• ISRCTN95654194 • EudraCT 2009-014280-38 | TANDEM Trial | Foss A et al. (2020)
Foss A, Haydock R, Childs M, et al. TANDEM TRIAL: A factorial randomized controlled trial of dose and review schedule of bevacizumab (Avastin) for neovascular macular degeneration in the East Midlands. BMJ Open Ophthalmology, 2020;5: e000588.
Locations
Conducted in five UK National Health Service (NHS) hospitals
Study Period
November 2010 - March 2017
Study Design
Multicenter, 2×2 factorial, double-masked, non-inferiority randomized controlled trial
Study Population
Experimental Group
Control Group
Follow-up Time: Median (IQR): 15 (9-27) months
Outcomes
Durability
Not reported.
Vision
Distance Visual Acuity (VA) Distance Visual Acuity (VA) at 9 months (low dose vs. standard dose):
• Low dose: 62.4 (SD 16.9)
• Standard dose: 63.9 (SD 16.3)
• Difference: -0.96 (95% CI -2.08 to 0.17) Distance Visual Acuity (VA) at 9 months (Bimonthly vs. Monthly):
• Bimonthly: 63.5 (SD 14.2)
• Monthly: 63.4 (SD 15.2)
• Difference: 0.13 (95% CI -0.99 to 1.25)
Other
Efficacy: Progression Outcomes Vision Deterioration (Primary Outcome) The number of participants with the primary outcome:
• Low dose: 32% (145/455)
• Standard dose: 31% (138/449)
• Bimonthly review: 36% (160/448)
• Monthly review: 27% (123/456) Time to vision deterioration:
• Low dose vs. standard dose: HR = 1.07 (95% CI: 0.80 to 1.42)
• Bimonthly vs. monthly review: HR = 1.45 (95% CI: 1.09 to 1.94) Median survival time before vision deterioration:
• Low dose: 3.2 years
• Standard dose: 3.6 years
• Bimonthly review: 3.0 years
• Monthly review: 3.6 years Development of Atrophy Patients with the development of atrophy:
• Low dose: 4%
• Standard dose: 3%
• Bimonthly review: 5%
• Monthly review: 4%
Immunognicity
Not reported.
Pharmokinetics
Not reported.
Anatomic
Not reported.
Safety
AEs
• A large number of AEs were reported, but few adverse reactions.
• The only difference between the groups relates to more conjunctival hemorrhages and injection site reactions reported in the monthly regimen.
Conclusion
The standard dose of bevacizumab can be halved without compromising efficacy. However, bimonthly review was not non-inferior to monthly review in preventing vision deterioration.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “Study participants, investigators, clinical assessors, and injectors were masked to drug dose allocation throughout the trial…” There is no information on the method of randomization. “Participant baseline characteristics were well balanced across the groups.”
Missing Outcome Data
Some concerns
Note: There is no information on how the missingness was dealt with in this study. However, the total missingness for each group was all <2%, and the proportion is balanced.
Selection of the Reported Results
Low risk Note: registration with protocol
Deviations from Intended Observations
Low risk Note: “Study participants, investigators, clinical assessors, and injectors were masked to drug dose allocation throughout the trial…” “Participants were analysed according to randomised allocation, regardless of adherence, following intention-to-treat principles, with eyes as the primary unit of analysis.”
Measurement of the Outcome
Low risk Note: “Study participants, investigators, clinical assessors, and injectors were masked to drug dose allocation throughout the trial…” “VA was measured bimonthly, and any deterioration in vision considered to meet the criterion for the primary outcome was confirmed by a refraction and repeat vision measurement.”
Overall
Some concerns
Categories: Wet AMD