Incorporating allocation concealment and blinding in randomised controlled trials

These methods are prone to get unblinded at any point of trial conduction. Both the active drugs can be taken out from their packaging and repacked in similar looking opaque containers. The containers can be labeled according to randomization. The observer can be blinded by separating the room where the person is dispensing the drug and the person observing the effects of the drug. There might be untoward effects in which the trial can be unblinded. The curiosity of participants or staff, differences in taste and smell of the drug, and placebo or a cross-over study are such instances.

Ideal placebos are not always easy to procure or manufacture. Thus, the assessment of blinding should be done prior to the decoding of randomization. The participants, investigators, and staff are asked to guess what the participants had received. For individual patient during an emergency, e. A surgical discipline is tested against a medical therapy, e. Researchers should ensure that the outcomes being measured are as objective as possible.

In addition, a duplicate assessment of outcome may be considered and researchers should report the level of agreement achieved. Expertise-based trial design- It can be done for surgical procedures, where patients are randomly assigned to different surgeons. Partial blinding- Sometimes, independent blinded evaluators may be sufficient to reduce bias. Limitations and potential biases due to lack of blinding need to be acknowledged and discussed.

Every researcher tries to prove his hypothesis as correct. If the investigator knows the randomization, such bias can lead to an imbalance in the study and wrong conclusions can be drawn. Such bias can be avoided by the following allocation of concealment techniques:. Third party randomization by phone or pharmacy. In large multi-centric trials, interactive-voice-response-service is used to ensure the allocation concealment in different centers.

Sequentially numbered, opaque, sealed envelope SNOSE technique: the randomization group is written on a paper and is kept in an opaque sealed envelope. The envelope is labeled with a serial number. The investigator opens the sealed envelope once the patient has consented to participate and then assigns the treatment group accordingly. Sequentially numbered opaque containers: Similar to SNOSE, but here, instead of a piece of paper, the medicines are stored in opaque containers according to randomization, and there is no possibility of the dispenser to know which medicine is kept in which container.

To conclude, a randomized controlled trial RCT is the gold-standard study design to evaluate any therapeutic method and carries the highest level of evidence Level I b. Undoubtedly, as a researcher, we all are interested in conducting an RCT and contribute to the knowledge of the scientific world. Choosing the correct control group and avoiding biases are the most important aspect of any RCT.

There can be a situation where blinding is not possible because of operational issues, but in every trial, effort should be thrust on randomization, which can eliminate two major biases: the bias of selection and confounding bias.

Proper randomization would ensure that the baseline confounders are balanced lest; complex statistical methods are called for balancing them e. This article is an attempt to provide practical tips for the researchers interested in a clinical trial, so that the data generated is more valid and credible. National Center for Biotechnology Information , U. Indian Dermatol Online J. Published online Aug Author information Article notes Copyright and License information Disclaimer.

Address for correspondence: Dr. E-mail: moc. Received Apr; Accepted May. This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4. This article has been cited by other articles in PMC. First, Ken Schulz and others have shown us that randomisation, blinding, and concealment of allocation make a difference to the accuracy of trial reports. Second, Phillip Devereaux and others have taken us to task for failing to report these important features of clinical trials.

Readers will find that abstracts of trials now include whether the randomisation was concealed from those responsible for entering patients into trials and who was blinded to treatment allocation during the trial.

Unfortunately, our experience to date shows that it is not always possible to acquire an unequivocal answer from authors about blinding or allocation concealment. Or the investigator indicates that sealed envelopes were used to conceal randomisation, but whether the envelopes were opaque is not indicated.

In doing so, we do not mean to offend investigators who have done their best to protect their trials from bias; rather, we wish to protect readers from us, the editors, conveying a sense of false security about studies for which we remain uncertain about the method used for concealment or blinding.

The definitions that we will use for the categories of allocation concealment are as follows:. Allocation concealed: the authors were deemed to have taken adequate measures to conceal allocation to study group assignments from those responsible for assessing patients for entry in the trial eg, central randomisation; numbered, opaque, sealed envelopes; sealed envelopes from a closed bag; numbered or coded bottles or containers; drugs prepared by the pharmacy; or other descriptions that contain elements convincing of concealment.

Allocation not concealed: the authors were deemed not to have taken adequate measures to conceal allocation to study group assignments from those responsible for assessing patients for entry in the trial eg, no concealment procedure, sealed envelopes that were not opaque, or other descriptions that contain elements not convincing of concealment.

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Necessary Necessary. Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information. Non Necessary non-necessary. Determining the feasibility of blinding patients is usually simple. If the trial involves 2 similar procedures such as a comparison of division versus nondivision of the short gastric vessels during laparoscopic Nissen fundoplication 13 , trialists may incorporate blinding by simply not informing patients of their treatment allocation.

If, however, researchers are comparing surgical therapy to nonoperative management such as a comparison of surgery versus surveillance for small aneurysms 14 , patients can only be blinded with ethically questionable methods like sham surgery.

Although surgeons can rarely be blinded, it may be possible for researchers to blind other members of the treatment team and thus limit the potential for differential treatment. For example, whereas surgeons would clearly need to know whether patients were assigned to the division or nondivision group of the fundoplication study, 13 the nurses, dieticians and other practitioners administering postoperative care could feasibly have been blinded by simply not informing them of the group allocation.

In some cases, this might require more creative but feasible blinding techniques such as covering different incisions with large dressings. Similarly, the individuals collecting data or adjudicating outcomes may often be blinded by use of relatively simple techniques.

The reviewers considered 3 techniques of blinding that could have been incorporated into these trials: using an independent individual unaware of the treatment allocation; concealing incisions or scars; and digitally altering radiographs to mask the type of implant Fig. Example of creative techniques to blind radiographs of femoral neck fracture reduction, fixated with either a dynamic hip screw or 3 cannulated screws. Whereas researchers should search for creative methods such as these to blind individuals in their trials, if they choose to incorporate a novel technique such as manipulation of radiographs , they must ensure that the blinding process itself does not introduce bias by impairing the ability to accurately assess the outcome.

Ideally, trialists will also test the successfulness of the blinding, although this should be undertaken before initiating a trial because there are dangers to testing the success of blinding once a trial has been completed. Finally, researchers can always blind the individuals performing the statistical analysis by simply labelling the groups with nonidentifying terms such as A and B.

Although this seems intuitive, surprisingly few researchers actually report blinding the data analysts in trials. Despite careful consideration of methods to blind individuals in trials, situations will invariably arise when some or all groups of individuals simply cannot ethically be blinded.

Surgical researchers must accept this reality and incorporate other strategies to minimize bias when blinding is not possible. When patients or clinicians cannot be blinded, trialists should ensure that the 2 or more allocation groups are, apart from the intervention, treated as equally as possible.

This may involve standardizing the care of participants such as cointerventions, frequency of follow-up and management of complications. Alternatively, researchers may choose to use an expertise-based trial design, in which patients are randomly assigned to different surgeons that each perform one intervention. Unfortunately, expertise-based trials do not address the potential biases that may be introduced by the lack of participant blinding and may not be appropriate for all research questions.

When data collectors or outcome adjudicators cannot be blinded, researchers should ensure that the outcomes being measured are as objective as possible.

Furthermore, the outcomes should be reliable although reliable outcomes are preferable whether or not the assessors are blinded. Finally, researchers should consider using duplicate assessment of outcomes and reporting the level of agreement achieved by the assessors. Even if researchers incorporate these methodologic precautions, they should acknowledge the limitations and potential biases introduced by the lack of blinding in the discussion section of the publication.

Blinding is an important methodologic feature of RCTs to minimize bias and maximize the validity of the results. Researchers should strive to blind participants, surgeons, other practitioners, data collectors, outcome adjudicators, data analysts and any other individuals involved in the trial.

Useful tips for surgical researchers are provided in Box 1. Although few surgical trials currently incorporate blinding, it may be possible to achieve blinding using novel, creative techniques. If blinding is not possible, researchers should incorporate other methodologic safeguards but should understand and acknowledge the limitations of these strategies.