Presentation is loading. Please wait.

Presentation is loading. Please wait.

Sponsored by the National Eye Institute,

Similar presentations

Presentation on theme: "Sponsored by the National Eye Institute,"— Presentation transcript:

1 Sponsored by the National Eye Institute,
An Evaluation of Study Participant Masking of Intraocular Injections in a Randomized Clinical Trial Sponsored by the National Eye Institute, National Institutes of Health, U.S. Department of Health and Human Services

2 Background Bias in Clinical Trials
Minimizing bias in a randomized clinical trial is a critical consideration during trial design Randomization alone does not ensure unbiased experiment Types of Bias: Non-differential bias: Noise affecting outcomes of treatment groups equally Differential bias: Systematic differences in outcomes between treatment groups 2

3 Minimizing Differential Bias
Background Minimizing Differential Bias Participant masking is one method of minimizing differential bias The decision on whether to mask study participants to treatment should be based on: Subjectivity of trial outcomes Type of treatment Disease type

4 Purpose Describe a trial design which attempted to mask participants to treatment allocation Discuss rationale for masking in the trial Evaluate success of masking study participant to treatment assignment

5 Study Design Objective: Evaluate efficacy of 4 treatment groups on
diabetic macular edema (measured by visual acuity) Randomized Clinical Trial (multi-center) Sham Injection +Prompt Laser Ranibizumab Injection +Prompt Laser Ranibizumab Injection +Deferred Laser Triamcinolone Injection +Prompt Laser Visits every 4 weeks through 52 weeks 52 Week Visit Primary Outcome

6 Study Design Participants with 1 study eye; randomized to 1 of 4 treatment groups Participants with 2 study eyes; one eye randomized to 1 of the 3 study drug groups and sham+prompt laser in the other Sham + Laser Ranibizumab + Prompt Laser Ranibizumab + Deferred Laser Triamcinolone + Laser* Injection Intervals (Weeks) 4W Triam: 16W Sham: 4W-intermittently Injection Type Always Sham Always Real Sometimes sham and sometimes real Median (Quartiles) # of injections/13 possible 11 (8,13) 8 (6, 10) 9 (6, 11) Triam: 3 (2, 4) Sham: 5 (3, 7)

7 Masking Participants were masked through the 1-year primary outcome except those in the ranibizumab + deferred laser group in either eye investigators believed that a successful sham laser treatment was not feasible. Investigators were not masked.

8 Injection Procedure Pre/post injection procedures for sham and intraocular injections were identical Providone iodine prep of the conjunctiva Pre-, peri-, or post-injection antibiotics were at investigator discretion. Comparing real injections with sham injections, antibiotics were given: Pre- and post-injection 34% vs. 27% of the time Only pre-injection 9% vs. 12% of the time Only post-injection 21% vs. 14% of the time For sham, the hub of a syringe without a needle was pressed against the conjunctival surface


10 Why Mask Visual acuity testing requires a study participant response and knowledge of treatment group could affect test performance if he/she believes that the better or worse treatment was received Improving diabetes control can have an effect on diabetic macular edema and subsequently visual acuity. Knowledge of the treatment group could affect participant’s behavior in a way that could influence the course of the disease and the primary outcome measure Investigators believed masking would work 10

11 Assessing Masking Success
At the completion of the 1-year visit, a questionnaire was administered to each participant by the study coordinator; Do you think the injections you have been getting in the [left/right] eye during the study have been: real injections into the eye, sham injection, meaning that a needle has not been injected into the eye, or sometimes real and sometimes sham?

12 Results: Masking Questionnaire Participants with 1 Study Eye
Sham + Laser N=105 Ran + Prompt Laser Ran + Deferred Laser N=112 Triam + Laser N=118 Refused to answer question 4% 5% 2% Response N=101 N=100 N=106 N=116 Always Real 72% 88% 90% 55% Sometimes real/ sometimes sham 18% 12% 7% 44% Always Sham 10% 1%

13 Results: Masking Questionnaire Participants with 2 Study Eyes
Ranibizumab + Prompt Laser N=42 Ranibizumab + Deferred Laser Triamcinolone + Laser N=37 Refused to answer question 4% 21% 5% N=44 N=33 N=35 Injected eye Correct response 84% 88% 31% Incorrect response 16% 12% 69% Sham eye 30% 27% 14% 70% 73% 86%

14 Results - Subgroups Correctness of response within treatment group did not appear to differ by: Prior injection for DME Prior laser for DME Baseline visual acuity Age Gender Race and ethnicity

15 Relationship of Masking and Visual Acuity – Sham + Laser Group
Change in Visual Acuity Believed Sham Injections Always Given Believed Real Injections were Always or Sometimes Given Distribution of visual acuity change Improved ≥ 5 letters (≥ 1 line): N=60 10% 90% Changed ± 4 letters: N=29 7% 93% Worsened ≥ 5 letters (≥ 1 line): N=12 17% 83% Mean ± Standard Deviation 3.6 ± 8.1 6.0 ± 9.4

16 Discussion The results suggest that very few participants (4%) believed they received only sham injections in a randomized trial comparing sham ocular injections with real ocular injections. Even when visual acuity outcomes did not improve or worsened, the study participant’s perception as to whether a sham or real injection was received did not appear to be influenced.

17 Summary Compared with the participants who received sham injections only, participants in the treatment group that received both real and sham injections in the same eye more often thought that a sham injection was at least sometimes given (28% vs. 45%, P-value = 0.009). This may imply that a participant is more likely to identify a sham injection when also receiving a real injection in the same eye. It appears that participants with two study eyes believe sham injections were always given in the sham eye (24% in this study) compared with participants with only one study eye (10% in this study).

18 Conclusion Sham intraocular injections can mask participants to treatment group assignments successfully when a procedure that attempts to mimic a real injection is followed. Although still successful, the success of masking potentially is reduced for participants who receive real injections in 1 eye and sham injections in the other, or receive both a sham injection and a real injection in the same eye. This study did not assess the bias in measuring visual acuity that may occur when participants receiving intraocular injections are not masked to treatment assignment.

Download ppt "Sponsored by the National Eye Institute,"

Similar presentations

Ads by Google