ArtifactAssessment that contains a series of nested ratings to document the risk of bias assessment of an Evidence resource (id = "risk-of-bias-example")

<?xml version="1.0" encoding="UTF-8"?>

<ArtifactAssessment xmlns="http://hl7.org/fhir">
  <id value="risk-of-bias-example"/> 
  <identifier> 
    <type> 
      <text value="FEvIR Object Identifier"/> 
    </type> 
    <system value="https://fevir.net"/> 
    <value value="27751"/> 
    <assigner> 
      <display value="Computable Publishing LLC"/> 
    </assigner> 
  </identifier> 
  <date value="2021-11-02T14:31:30.239Z"/> 
  <copyright value="https://creativecommons.org/licenses/by-nc-sa/4.0/"/> 
  <lastReviewDate value="2021-08-11"/> 
  <artifactCanonical value="http://fevir.net/resources/Evidence/7637"/> 
  <content> 
    <informationType value="rating"/> 
    <type> 
      <coding> 
        <system value="http://hl7.org/fhir/certainty-type"/> 
        <version value="6.0.0"/> 
        <code value="RiskOfBias"/> 
        <display value="Risk of bias"/> 
        <userSelected value="true"/> 
      </coding> 
    </type> 
    <classifier> 
      <coding> 
        <system value="http://hl7.org/fhir/certainty-rating"/> 
        <version value="6.0.0"/> 
        <code value="extremely-serious-concern"/> 
        <display value="extremely serious concern"/> 
        <userSelected value="true"/> 
      </coding> 
    </classifier> 
    <author> 
      <display value="COVID-19 Knowledge Accelerator Evidence 7637 Authors (Brian S. Alper, Harold Lehmann,
       Ahmad Sofi-Mahmudi, Joanne Dehnbostel, Ilkka Kunnamo)"/> 
    </author> 
    <freeToShare value="true"/> 
    <component> 
      <summary value="Inclusion of suspected COVID-19 in 1 of 3 trials may introduce selection bias,
       but the impact appears limited."/> 
      <type> 
        <text value="Selection Bias"/> 
      </type> 
      <classifier> 
        <coding> 
          <system value="http://hl7.org/fhir/certainty-rating"/> 
          <version value="6.0.0"/> 
          <code value="no-concern"/> 
          <display value="no serious concern"/> 
          <userSelected value="true"/> 
        </coding> 
      </classifier> 
      <author> 
        <display value="Brian S. Alper, Joanne Dehnbostel, Muhammad Afzal"/> 
      </author> 
      <component> 
        <summary value="Definition of Selection Bias = A bias resulting from methods used to select subjects
         or data, factors that influence initial study participation, or differences between
         the study sample and the population of interest"/> 
      </component> 
    </component> 
    <component> 
      <summary value="The study design used response-adaptive randomization in which group assignment
       ratios could be modified during the trial on the basis of response-adaptive interim
       analyses to favor the assignment of patients to the treatment group showing greater
       benefit. The confounding by time (imbalanced randomization with time period) is
       not adequately reported to determine the potential influence on results or adequacy
       of adjusted analyses."/> 
      <type> 
        <text value="Confounding Covariate Bias"/> 
      </type> 
      <classifier> 
        <coding> 
          <system value="http://hl7.org/fhir/certainty-rating"/> 
          <version value="6.0.0"/> 
          <code value="serious-concern"/> 
          <display value="serious concern"/> 
          <userSelected value="true"/> 
        </coding> 
      </classifier> 
      <author> 
        <display value="Brian S. Alper, Ilkka Kunnamo, Alfonso Iorio, Joanne Dehnbostel, Harold Lehmann,
         Kenneth Wilkins; clarifying explanation reviewed by Janice Tufte"/> 
      </author> 
      <component> 
        <summary value="Definition of Confounding Covariate Bias = A situation in which the effect or association
         between an exposure and outcome is distorted by another variable. For confounding
         covariate bias to occur the distorting variable must be (1) associated with the
         exposure and the outcome, (2) not in the causal pathway between exposure and outcome,
         and (3) unequally distributed between the groups being compared."/> 
      </component> 
      <component> 
        <summary value="ATTACC implemented response-adaptive randomization on December 15, 2020, which
         led to imbalanced randomization. No data reported to determine if intervention-specific
         outcome rates were similar or different before and after December 15, 2020 in the
         ATTACC cohort."/> 
      </component> 
      <component> 
        <summary value="Insufficient details reported to judge whether there is an imbalance in outcomes
         related to the adaptive randomization which in turn could be used to judge the
         validity of adjustment methods in the statistical model for this concern and the
         appropriateness of any sensitivity analyses."/> 
      </component> 
      <component> 
        <summary value="Response-adaptive randomization led to imbalanced randomization."/> 
        <type> 
          <text value="Allocation Bias"/> 
        </type> 
        <classifier> 
          <text value="Adaptive randomization is not a concern by itself, only if it results in a confounding
           difference."/> 
        </classifier> 
        <author> 
          <display value="Brian S. Alper, Joanne Dehnbostel, Harold Lehmann, Kenneth Wilkins"/> 
        </author> 
        <component> 
          <summary value="Definition of Allocation Bias = A confounding covariate bias resulting from methods
           for assignment of the independent variable by the investigator to evaluate a response
           or outcome."/> 
        </component> 
        <component> 
          <summary value="ATTACC implemented response-adaptive randomization on December 15, 2020, which
           led to imbalanced randomization."/> 
        </component> 
      </component> 
      <component> 
        <summary value="There is an unequal distribution of calendar time between the groups being compared."/> 
        <type> 
          <text value="Confounding difference"/> 
        </type> 
        <classifier> 
          <coding> 
            <system value="http://hl7.org/fhir/certainty-rating"/> 
            <version value="6.0.0"/> 
            <code value="serious-concern"/> 
            <display value="serious concern"/> 
            <userSelected value="true"/> 
          </coding> 
        </classifier> 
        <author> 
          <display value="Brian S. Alper, Joanne Dehnbostel, Harold Lehmann, Kenneth Wilkins"/> 
        </author> 
        <component> 
          <summary value="Definition of Confounding difference = A confounding covariate bias in which the
           unequal distribution of a potentially distorting variable is recognized."/> 
        </component> 
        <component> 
          <summary value="Incomplete reporting limits the determination of the potential degree of influence
           of calendar time."/> 
        </component> 
        <component> 
          <summary value="There is evidence of potential for calendar time to influence the results: In an
           observational study of 18,508 adults with laboratory-confirmed, COVID-19 associated
           hospitalization 'The percentage of hospitalized patients admitted to the ICU decreased
           from 37.8% in March to 20.5% in December' (Ann Intern Med 2021 Aug 10 https://www.acpjournals
          .org/doi/10.7326/M21-1991)."/> 
        </component> 
      </component> 
    </component> 
    <component> 
      <summary value="Awareness of treatment assignment may reduce clinical decision to initiate some
       types of &quot;organ support&quot; in patients with higher risk of major bleeding."/> 
      <type> 
        <text value="Performance Bias"/> 
      </type> 
      <classifier> 
        <coding> 
          <system value="http://hl7.org/fhir/certainty-rating"/> 
          <version value="6.0.0"/> 
          <code value="very-serious-concern"/> 
          <display value="very serious concern"/> 
          <userSelected value="true"/> 
        </coding> 
      </classifier> 
      <author> 
        <display value="Brian S. Alper, Joanne Dehnbostel, Harold Lehmann, Muhammad Afzal"/> 
      </author> 
      <component> 
        <summary value="Definition of Performance Bias = A bias resulting from differences between the
         received exposure and the intended exposure."/> 
      </component> 
      <component> 
        <summary value="Lack of blinding may explain reported differences in the primary outcome."/> 
        <type> 
          <text value="Inadequate blinding of intervention deliverers"/> 
        </type> 
        <classifier> 
          <coding> 
            <system value="http://hl7.org/fhir/certainty-rating"/> 
            <version value="6.0.0"/> 
            <code value="very-serious-concern"/> 
            <display value="very serious concern"/> 
            <userSelected value="true"/> 
          </coding> 
        </classifier> 
        <author> 
          <display value="Brian S. Alper; clarifying explanation reviewed by Janice Tufte"/> 
        </author> 
        <component> 
          <summary value="The absolute difference in survival without intubation was 1%, so 3% of the 4%
           absolute difference in the primary outcome can be considered &quot;organ support
           without intubation&quot;."/> 
        </component> 
        <component> 
          <summary value="The specific &quot;organ support without intubation&quot; was not reported. The
           methods for one of the included trials stated &quot;Organ Support is defined as
           receipt of invasive or non-invasive mechanical ventilation, high flow nasal oxygen,
           vasopressor therapy, or ECMO support&quot;"/> 
        </component> 
        <component> 
          <summary value="Awareness of treatment assignment may reduce clinical decision to initiate &quot;organ
           support without intubation&quot; in patients with higher risk of major bleeding."/> 
        </component> 
        <component> 
          <summary value="Definition of Inadequate blinding of intervention deliverers = A performance bias
           due to awareness of the allocated intervention by individuals providing or delivering
           the intervention."/> 
        </component> 
      </component> 
      <component> 
        <summary value="Crossover to other intervention in 20%"/> 
        <type> 
          <text value="Deviation from study intervention protocol"/> 
        </type> 
        <classifier> 
          <text value="degree of concern unclear"/> 
        </classifier> 
        <author> 
          <display value="Surbhi Shah, Brian S. Alper"/> 
        </author> 
        <component> 
          <summary value="Therapeutic dose anticoagulation (in the first 24-48 hours following randomization)
           was reported in 79.6% of the therapeutic arm and 0.9% of the usual care arm. (Table
           S3)"/> 
        </component> 
        <component> 
          <summary value="Definition of Deviation from study intervention protocol = A performance bias in
           which the intervention received differs from the intervention specified in the
           study protocol."/> 
        </component> 
      </component> 
      <component> 
        <summary value="We discussed whether they may be a bias related to limited adherence to anticoagulation.
         Because this was an inpatient population, we did not expect adherence problems
         that are more common with outpatient thromboprophylaxis."/> 
        <type> 
          <text value="Nonadherence of implementation"/> 
        </type> 
        <classifier> 
          <text value="limited concern"/> 
        </classifier> 
        <author> 
          <display value="COVID-19 Knowledge Accelerator Working Group discussion with Brian S. Alper, Ilkka
           Kunnamo, Joanne Dehnbostel; Performance Bias concern initially suggested by Harold
           Lehmann"/> 
        </author> 
        <component> 
          <summary value="Initial adherence to the protocol-assigned anticoagulation dose after randomization
           was 88.3% in the therapeutic-dose anticoagulation group and 98.3% in the thromboprophylaxis
           group (Table S3)."/> 
        </component> 
        <component> 
          <summary value="Definition of Nonadherence of implementation = A performance bias in which the
           intervention deliverers do not completely adhere to the expected intervention."/> 
        </component> 
      </component> 
    </component> 
    <component> 
      <summary value="The influence of awareness of treatment assignment by the treating clinicians on
       the initaition of organ support (which is the primary outcome) was already addressed
       as Performance Bias so is not repeated here as a bias in detecting the outcome."/> 
      <type> 
        <text value="Detection Bias"/> 
      </type> 
      <classifier> 
        <coding> 
          <system value="http://hl7.org/fhir/certainty-rating"/> 
          <version value="6.0.0"/> 
          <code value="no-concern"/> 
          <display value="no serious concern"/> 
          <userSelected value="true"/> 
        </coding> 
      </classifier> 
      <author> 
        <display value="Brian S. Alper, Joanne Dehnbostel, Muhammad Afzal"/> 
      </author> 
      <component> 
        <summary value="Definition of Detection Bias = A bias due to distortions in how variable values
         (data) are determined."/> 
      </component> 
    </component> 
    <component> 
      <summary value="Only 19 of 1190 (1.6%) therapeutic group and 6 of 1054 (0.6) prophylactic group
       were excluded after randomization."/> 
      <type> 
        <text value="Attrition Bias"/> 
      </type> 
      <classifier> 
        <coding> 
          <system value="http://hl7.org/fhir/certainty-rating"/> 
          <version value="6.0.0"/> 
          <code value="no-concern"/> 
          <display value="no serious concern"/> 
          <userSelected value="true"/> 
        </coding> 
      </classifier> 
      <author> 
        <display value="Brian S. Alper, Joanne Dehnbostel, Muhammad Afzal"/> 
      </author> 
      <component> 
        <summary value="Definition of Attrition Bias = A bias due to absence of expected participation
         or data collection after selection for study inclusion."/> 
      </component> 
    </component> 
    <component> 
      <summary value="It is unknown if the results are sensitive to the analytic method, and the stopping
       criteria were based on statistical significance and not magnitude of effect."/> 
      <type> 
        <text value="Analysis Bias"/> 
      </type> 
      <classifier> 
        <coding> 
          <system value="http://hl7.org/fhir/certainty-rating"/> 
          <version value="6.0.0"/> 
          <code value="very-serious-concern"/> 
          <display value="very serious concern"/> 
          <userSelected value="true"/> 
        </coding> 
      </classifier> 
      <author> 
        <display value="Brian S. Alper, Joanne Dehnbostel, Muhammad Afzal, Janice Tufte"/> 
      </author> 
      <component> 
        <summary value="Definition of Analysis Bias = A bias related to the analytic process applied to
         the data."/> 
      </component> 
      <component> 
        <summary value="A frequentist analysis is not reported so we cannot determine if the results are
         sensitive to the analytic method"/> 
        <type> 
          <text value="Bias related to selection of the analysis"/> 
        </type> 
        <classifier> 
          <coding> 
            <system value="http://hl7.org/fhir/certainty-rating"/> 
            <version value="6.0.0"/> 
            <code value="very-serious-concern"/> 
            <display value="very serious concern"/> 
            <userSelected value="true"/> 
          </coding> 
        </classifier> 
        <author> 
          <display value="Brian S. Alper, Joanne Dehnbostel, Muhammad Afzal, Janice Tufte"/> 
        </author> 
        <component> 
          <summary value="Definition of Bias related to selection of the analysis = An analysis bias due
           to inappropriate choice of analysis methods before the analysis is applied."/> 
        </component> 
        <component> 
          <summary value="There was no pre-specified frequentist analysis. There was no posthoc frequentist
           analysis reported."/> 
        </component> 
        <component> 
          <summary value="It is uncertain what a frequentist analysis would show and uncertain whether the
           choice of Bayesian analysis or frequentist analysis has a substantial influence
           on the results."/> 
        </component> 
      </component> 
      <component> 
        <summary value="The stopping criteria were based on statistical significance and not magnitude
         of effect."/> 
        <type> 
          <text value="Early trial termination"/> 
        </type> 
        <classifier> 
          <coding> 
            <system value="http://hl7.org/fhir/certainty-rating"/> 
            <version value="6.0.0"/> 
            <code value="very-serious-concern"/> 
            <display value="very serious concern"/> 
            <userSelected value="true"/> 
          </coding> 
        </classifier> 
        <author> 
          <display value="Brian S. Alper, Joanne Dehnbostel, Muhammad Afzal, Janice Tufte"/> 
        </author> 
        <component> 
          <summary value="There was no “minimally important difference”. So a 99% probability of having an
           odds ratio &gt; 1 (even if the magnitude of effect is infinitesimal) was used to
           decide it was time to stop the trial."/> 
        </component> 
      </component> 
    </component> 
  </content> 
  <content> 
    <informationType value="comment"/> 
    <summary value="Results not consistent with critically ill cohort."/> 
    <type> 
      <coding> 
        <system value="http://hl7.org/fhir/certainty-type"/> 
        <version value="6.0.0"/> 
        <code value="Inconsistency"/> 
        <display value="Inconsistency"/> 
        <userSelected value="true"/> 
      </coding> 
    </type> 
    <author> 
      <display value="Ilkka Kunnamo"/> 
    </author> 
  </content> 
</ArtifactAssessment>