Masking

Janet Holbrook, PhD, MPH

Johns Hopkins University

Copyright 2013 Johns Hopkins University and Janet Holbrook. All Rights Reserved.

Outline
n

Masking
- Definition
- Rationale
- Advantage and disadvantage

Masking
n
n

Synonymous with blinding

Treatment assignment is not known after randomization
- Patient, clinic personnel, evaluators, data processors, analyst,
independent review committee, sponsor . . .
- Single, double, triple, quadruple . . .
Not the same as concealment of treatment assignment prior to
randomization
- Concealment protects against selection bias

Rationale
n

To reduce bias related to prior knowledge or beliefs about

treatment effects on the performance of the trial and on the
reporting of outcomes
Promotes objectivity in:
- Data reporting
- Data collection and follow-up
- Concomitant treatments, testing, behaviors
- Outcome assessment
- Data interpretation

Level of Masking
n

Single
- Participant is masked
Double
- Participant and clinical investigator are masked
Triple
- Participant and clinical investigator and others are masked
Others: outcome evaluators, data analysts, data
monitoring committees, sponsors . . .

Advantages/Disadvantages
n

Advantages of masking
- Protects against performance/reporting bias
Data collection and follow-up
Outcome assessment and reporting
Other care received during the trial
Interpretation of results
Disadvantages
- May be logistically or ethically impossible
- May not reflect clinical care practices
Concomitant care
- Increases logistical complexity
- Increased cost

Bias Protection by Level of Masking

Level of Masking
Bias protection

None

Single

Double

Triple

Data reporting

No

Yes

Yes

Yes

Data collection/follow-up

No

No

Yes

Yes

Concomitant care, testing,

behaviors

No

No/No/
Yes

Yes

Yes

Outcome assessment

No

No

Yes

Yes

Data analysis/interpretation

No

No

No

Yes
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Decision to Mask Treatments

n

Is it ethical?
- Exposure to risk with placebo treatment, e.g., sham surgery,
IV infusions
- Risk increased if investigator/caregiver doesnt know
- Viable unmasking plan
Is it possible?
- Distinctive characteristic, behavioral intervention, community
interventions may make it impossible
- Can you make the treatments seem identical
Or
- Can you create a placebo for each treatment, frequently
called a dummy treatment

Decision to Mask Treatments (cont.)

n

Trial design features

- Type of outcomes, more important for subjective ones
- Will outcome evaluation be masked regardless?
- What are the comparison groups?
No treatment
Active control
Is it feasible?
- Cost-benefit
- Is it practical? Would participants adhere to it?
- Effectiveness of masking

UnmaskingPlanned
n

Strategy depends on closeout design

- Common closeout: all participants finish at same time
Closeout visit or phone call
- Anniversary closeout: participants finish at different times
Should not be revealed to clinic staff
Letter to participant at the exit interview
Instructions for ways to continue treatment
Collect data on participant and clinic guess as to treatment
assignment before you reveal it
Need to document, provide primary care physician with information

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UnmaskingUnplanned
n

Discouragedusually not required to treat patient

- Stop drug for adverse events
Extenuating circumstances
- Next step in treatment may be more problematic
- Overdoses
Easy access without being too easy
- Weigh risks
Methods
- On study drug container
- At clinics, semi-independent person responsible
- Contact parties responsible for randomizing/masking
- 24-hour call line
- Web site

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