Examining the Impact of Real-World Evidence on Medical Product Development Proceedings of a Workshop Series (2019) / Chapter Skim
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8 Obscuring Intervention Allocation in Trials to Generate Real-World Evidence: Why, Who, and How?
8 Obscuring Intervention Allocation in Trials to Generate Real-World Evidence: Why, Who, and How?
Pages 117-132
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From page 117... ...
• Decisions on blinding can also be influenced by practical con siderations, such as effects on study cost, feasibility of masking or delivering the treatments, patient preferences, and the gener alizability of data from blinded study sites. (Dreyer, Reynolds, Smith)
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From page 118... ...
This session in the third workshop examined the topic of blinding, and session moderator Jonathan Watanabe, associate professor of clinical pharmacy and National Academy of Medicine Anniversary Fellow in Pharmacy, University of California, San Diego, asked participants to consider the following: • How might variability in knowledge of treatment group assignment affect provider and patient adherence and outcomes? • How might variability in knowledge of treatment assignment affect study cost and reliability?
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From page 119... ...
Center for Chronic Disease Outcomes Research, told workshop participants about the INVESTED (INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure) trial.
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From page 120... ...
Without double blinding, these perceptions may have resulted in systematic bias in terms of patients presenting at the hospital, or providers urging hospitalization.
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From page 121... ...
. The INTERSEPT trial tested two oral antipsychotic drugs, and was not blinded because of differences in known side effect profiles, additional blood draw monitoring required by only one of the drugs, and because the investigators judged that it was unethical for this study to be blinded because that may have inhibited individual providers' ability to give the best care to their patients.
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From page 122... ...
How might concealing treatment allocation from patients and/or providers reduce biases due to preferences or expectations?
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From page 123... ...
The risk/benefit ratio of trial participation? FIGURE 8-2 Decision aid on questions to consider regarding when and whether to obscure intervention allocation (commonly known as blinding)
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From page 124... ...
Critchlow added that this sort of quantification could be risky because it could make the researchers "feel better about making a decision that may not be based on something real." Richard Platt wondered if some of these a priori decisions could be based on empirical data on bias from previous research -- for example, data on how aggressively vaccinated patients are treated versus nonvaccinated patients. Vardeny said that vaccinated patients are so different BOX 8-2 Feedback on the Decision Aid as Discussed by Individual Workshop Participants Several workshop participants offered specific feedback on the decision aid "Obscuring Intervention Allocation in Trials to Generate Real-World Evidence: Why, Who, and How?
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From page 125... ...
Smith agreed that making a decision about blinding depends on the research question. For example, he said, if the research is seeking answers about whether patients are more likely to adhere to an injectable therapy or to an oral daily tablet, a blinded study cannot answer that question.
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From page 126... ...
For example, if there are uncertainties about efficacy, blinding may be necessary, whereas if there are uncertainties about effectiveness in the real world, blinding would not be warranted. London explained that real-world effectiveness is a function of two variables: ensemble efficacy and utilization factors.
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From page 127... ...
Risks of Blinding When blinding is necessary to fully understand the effectiveness of an intervention, participants in the control group receive some sort of placebo drug or intervention, London said. This could range from a sugar pill, to a sham surgery that is "largely theater," to invasive surgical procedures such as implanting cannulas in the brain to deliver saline in Parkinson's trials, said London.
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From page 128... ...
If the real knee surgery does not have any benefit, London said, the risks far outweigh the benefits. Both the risks from the placebo or sham procedure and the risks from receiving a potentially ineffective active intervention should be communicated to participants, London said.
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From page 129... ...
Patient Preferences One question on the decision aid asks, "How might procedures necessary to conceal treatment allocation from patients and/or providers impact the acceptability of trial participation to patients and/or providers? " Smith said the best way to answer this question is to ask the patients directly.
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From page 130... ...
Critchlow added that in a context where there are fewer therapeutic options, patients might be more willing to take the risk of participating in a trial, whereas in a context with plenty of existing therapeutic options, the risk–benefit analysis of patients and providers is quite different. On another patient-related topic, John Burch, an investor with the Mid-America Angels Capital Network, asked whether participants in a blinded trial are ever able to get information about which treatment they received.
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From page 131... ...
Dreyer noted that for some outcomes, patient perception likely has no effect -- "dead is dead." Graham added that depending on the time line of the study, patient perception bias may wane over time. For example, if a patient gets a vaccine and feels ill 3 weeks later, does the patient's initial idea of what treatment he received still affect his likelihood of seeking medical care?
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From page 132... ...
. Because of this, patients who are already at high risk of MI may be prescribed acetaminophen instead of NSAIDs, which results in a larger-than-expected group of acetaminophen patients experiencing MI.
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