This document defines allocation concealment and discusses its importance in clinical trials. Allocation concealment refers to preventing investigators from knowing the next treatment assignment so they cannot influence which participants are assigned to different study arms. Inadequate allocation concealment can introduce bias and invalidate trial results. The document provides examples of how allocation concealment can be deciphered or biased and recommends methods like sequentially numbered sealed envelopes and centralized randomization to properly conceal allocations.

1. ALLOCATION CONCEALMENT
Tulasi Raman P

2. DEFINITION
 Allocation concealment refers to preventing
the next assignment in the clinical trial from
being known.
 Allocation concealment refers to the
technique used to implement the sequence,
not to generate it.

3.  Allocation concealment has nothing directly
to do with randomization.
 It has nothing to do with blinding doctors or
patients while getting or giving therapy.
 It makes sure that patients enroll into a study
without knowing which arm of the study they
will be assigned to and preventing the
providers or researchers on site from
interfering with the randomized allocation
process.

4. EXAMPLE 1:
 If the referring health care provider knows
the next subject will be allocated to
Slimmenow, he/she may be inclined to try to
help a certain patient he/she thinks may
benefit more.
 This will introduce selection bias that the
randomization was designed to eliminate.

5. EXAMPLE 2:
 Subjects are probably hoping to be randomized
to Slimmenow. If a subject becomes aware of
the allocation scheme prior to enrollment,
knowledge of allocation to placebo might cause
the subject to refuse to participate entirely.
 Or, the subject may wait until the allocation is to
the active drug before enrolling.
 Again, the results are loss of randomization and
introduction of bias.

6. IMPORTANCE OF ALLOCATION CONCEALMENT
Trials that used inadequate or unclear
allocation concealment:
1. Yield up to 40% larger estimates of effect.
2. Yield greater heterogeneity in results.
3. Allows bias to seep into trials.

7.  Moreover, the results of such a trial can be more
damaging than similar results from an explicitly
observational research study.
 Biases are usually assumed and acknowledged
in observational studies, and the statistical
analysis and eventual interpretation attempt to
take those biases into account.
 Conversely, studies labeled as randomized are
frequently assumed to be free of bias.

8.  Consequently, the credibility of randomized
controlled trials lends support to faster and
greater changes in clinical or preventive
management.
 If it is based on a compromised study,
squanders scarce health resources, or even
worse, harms peoples’ health.

9. DECIPHERING REASONS:
 Researchers might want certain patients to
benefit from one of the treatments, or the trial
results to confirm their beliefs.
 An absence of knowledge of the scientific
ramifications of such actions.
 the deciphering of the allocation scheme
might frequently become too great an
intellectual challenge to resist

10. EXAMPLES OF METHODS OF DECIPHERING
ALLOCATION CONCEALMENT
1. Holding translucent envelopes up to bright lights to
reveal upcoming assignment.
2. Opening unsealed assignment envelopes.
3. Opening a well-sealed, opaque envelope in advance
of consent.
4. Opening unnumbered envelopes until desired
allocation found.
5. Determining different weights of the assignment
envelopes.
6. Asking a central randomization center for the next
several assignments all at once.
7. Deciphering assignments to active drug or placebo
based on appearance of drug container labels.

11. SUGGESTED MINIMUM AND EXPANDED
DESCRIPTIONS OF ALLOCATION CONCEALMENT
1. Sequentially numbered, opaque, sealed
envelopes (“SNOSE”).
2. Sequentially numbered containers.
3. Pharmacy controlled.
4. Central randomization.

12. 1. SEQUENTIALLY NUMBERED, OPAQUE, SEALED
ENVELOPES (“SNOSE”)
 Description of details on how tampering and
discovery was prevented (eg, carbon paper
lined to create an audit trail, aluminum foil or
cardboard placed inside to prevent “hot
lighting”)

13. 2. SEQUENTIALLY NUMBERED CONTAINERS
 Description provides details of no detectable
differences between containers. Containers
were equal in weight, similar in appearance,
and tamper-proof.

14. 3. PHARMACY CONTROLLED
 Description provides indications that the
researchers developed or validated a proper
randomization scheme for use by the
pharmacy. Description that the pharmacy
was provided instruction in allocation
concealment.

15. 4. CENTRAL RANDOMIZATION
 Mechanism for contact is described (eg,
telephone, e-mail, fax). Precautions taken to
ensure enrollment prior to allocation as well
as description of training for individuals
staffing the central office are provided.

16. CONCLUSION
 Proper randomisation remains the only way to avoid
selection and confounding biases.
 Randomised controlled trials antagonise human
beings by frustrating their clinical inclinations. Thus,
many involved with trials will be tempted to
undermine randomisation, if afforded the opportunity
to decipher assignments.
 To minimise the effect of this human tendency,
trialists must devote meticulous attention to
concealment of allocation schemes, because proper
randomisation hinges on adequate allocation
concealment.

17. THANK YOU