Transcutaneous bilirubinometry versus total serum bilirubin measurement for newborns
Appendices
Appendix 1. Embase search strategy
Our search strategy for Embase OVID below was developed by discussion between the author team and the Cochrane Neonatal Group's Trials Search Co‐ordinator. We will adapt it for use in other databases.
(infant, newborn or neonat* or premature or very low birth weight or low birth weight or VLBW or LBW or infan*) AND ((transcutaneous adj2 bilirubin) OR TcB OR bilicheck OR bilichek OR JM‐103 OR JM‐105 OR bilirubinomet* AND ((blood* or serum) adj bilirubin) OR TsB OR spectrophotomet*).mp
Appendix 2. QUADAS‐2 tool
QUADAS‐2 tool: Risk of bias and applicability judgements
| Domain 1: Patient selection | |
| A. Risk of bias | |
| 1. Was a consecutive or random sample of patients enrolled? | Yes/No/Unclear "Yes" if it is clearly stated in the paper that a consecutive or a random sample of patients was enrolled. "No" if the patients were not recruited consecutively or the sample was not random. "Unclear" if there is insufficient information to answer "yes" or "no". |
| 2. Was a case‐control design avoided? | Yes/No/Unclear The answer will always be "yes" since the review will exclude case‐control studies. |
| 3. Did the study avoid inappropriate exclusions? | Yes/No/Unclear "Yes" if the stated inclusion and exclusion criteria are clear and appropriate. "No" if the stated inclusion and exclusion criteria include inappropriate subjects. "Unclear" if insufficient information is available to answer "yes" or "no". |
| 4.Could the selection of patients have introduced bias? | RISK: Yes/No/Unclear "No" if questions 1 and 3 are answered "yes" (Low risk). "Yes" if questions 1 or 3 is answered "no" (High risk). "Unclear" if insufficient information is available to answer questions 1 or 3. |
| B. Concerns regarding applicability | |
| Describe included patients (prior testing, presentation, intended use of index test and setting): | |
| 1. Is there concern that the included patients do not match the review question? | CONCERN: Yes/No/Unclear "No" when the study population represents an unselected sample of newborns expected to receive TcB assessment for hyperbilirubinaemia (Low). "Yes" if included patients are inherently different from those expected to receive TcB assessment for hyperbilirubinaemia (High). "Unclear" if there is insufficient information to make a judgement on the patient inclusion (Unclear). |
| Domain 2: Index test(s) (if more than 1 index test was used, please complete for each test) | |
| A. Risk of bias | |
| Describe the index test and how it was conducted and interpreted: | |
| 1.· Were the index test results interpreted without knowledge of the results of the reference standard? | Yes/No/Unclear “Yes” if the paper states that the index test is interpreted by individual(s) who were unaware of the results of the reference test(s). “No” if the results of the index test were known by the individuals performing the reference test, or if the same individual performed both tests. "Unclear" if there is insufficient information to answer "yes" or "no". |
| 2. If a threshold was used, was it pre‐specified? | Yes/No/Unclear "Yes" if a pre‐specified positivity threshold was stated. "No" if a threshold was not pre‐specified. "Unclear" if there is insufficient information to answer "yes"or "no". |
| 3.Could the conduct or interpretation of the index test have introduced bias? | RISK: Low/High/Unclear “No” if questions 1 and 2 are answered'"yes" (Low risk). “Yes” if questions 1 or 2 is answered "no" (High risk). “Unclear if there is insufficient information available to answer "yes" or "no" (Unclear risk). |
| B. Concerns regarding applicability | |
| Is there concern that the index test, its conduct, or interpretation differ from the review question? | CONCERN: Low/High/Unclear “No” if there are no concerns based on the information available (Low). “Yes” if the index test is not TcB measurement for hyperbilirubinaemia in newborns or if the conduct of the test or its interpretation is not applicable to the review question (High). "Unclear" if there is insufficient information to answer "yes" or "no". |
| Domain 3: Reference standard | |
| A. Risk of bias | |
| Describe the reference standard and how it was conducted and interpreted: | |
| 1 Is the reference standard likely to correctly classify the target condition? | Yes/No/Unclear "Yes" if the reference standard is TsB measured by one of the laboratory methods mentioned in this protocol. "No" if the above condition is not met. "Unclear" if there is insufficient information to answer "yes" or "no". |
| 2 Were the reference standard results interpreted without knowledge of the results of the index test? | Yes/No/Unclear "Yes" if it is stated that the individual performing/interpreting the results of the reference standard was kept unaware of the results of the index test. "No" if the results of the TcB measurement were known to the individual performing/interpreting the reference standard. "Unclear" if there is insufficient information to answer "yes" or "no". |
| Could the reference standard, its conduct, or its interpretation have introduced bias? | RISK: Low/High/Unclear "No" if questions 1 and 2 are answered "yes" (Low risk). "Yes" if question 1 or 2 is answered "no" (High risk). "Unclear" if there is insufficient information to answer "yes" or "no". |
| B. Concerns regarding applicability | |
| Is there concern that the target condition as defined by the reference standard does not match the review question? | CONCERN: Low/High/Unclear "No" if the target condition is hyperbilirubinaemia in newborns (Low). "Yes" if the target condition is not hyperbilirubinaemia in newborns or it is not clearly stated (High). "Unclear" if there is insufficient information available to answer "yes"or "no" (Unclear). |
| Domain 4: Flow and timing | |
| A. Risk of bias | |
| Describe any patients who did not receive the index test(s) and/or reference standard or who were excluded from the 2x2 table (refer to flow diagram): Describe the time interval and any interventions between index test(s) and reference standard: | |
| 1.· Was there an appropriate interval between index test(s) and reference standard? | Yes/No/Unclear "Yes" if the time between the index test and the reference standard is less than 30 minutes. "No" if the time between the index test and the reference standard is longer than 30 minutes for a significant proportion of the patients. "Unclear" if insufficient information is available to answer "yes" or "no". |
| ·2. Did all patients receive a reference standard? | Yes/No/Unclear "Yes" if all the patients who received the index test received a reference standard. "No" if not all the patients who received the index test received a reference standard. "Unclear" if there is insufficient information to answer "yes" or "no". |
| ·3. Did patients receive the same reference standard? | Yes/No/Unclear “Yes” if the same reference standard was used for all patients. “No” if different reference standards were used. “Unclear” if there is insufficient information to answer "yes" or "no". |
| 4.· Were all patients included in the analysis? | Yes/No/Unclear “Yes”if all patients were included in the analysis,or if any withdrawals or exclusions are adequately explained with a flow chart. “No” if withdrawals or exclusions are not explained or accounted for. “Unclear” there is insufficient information to answer "yes" or "no". |
| Could the patient flow have introduced bias? | RISK: Low/High/Unclear "No" if questions 1, 2, 3 and 4 are answered "yes" (Low risk). "Yes" if any of the four questions is answered "no" (High risk). "Unclear" if there is insufficient information to answer "yes" or "no" (Unclear risk). |
TcB: Transcutaneous bilirubin
TsB: Total serum bilirubin
| [Study ID] | First author, year of publication |
| Type of study | Journal article, unpublished data |
| Participants | Sample size Country of study Baseline characteristics (gestational age, postnatal age, race, body weight) |
| Study design | Retrospective/prospective design Sample (consecutive, random or unclear) |
| Study criteria | Inclusion criteria Exclusion criteria |
| Reference standard | Name of assay/manufacturer Name of instrument Cut‐off values Time between reference standard performance and TcB measurement Blinding of operator to TcB result |
| Index test | Name of device Cut‐off values Operator training site of measurement (forehead, sternum) |
| Target condition | Universal screening of newborns for hyperbilirubinaemia Diagnostic determination of hyperbilirubinaemia in visibly jaundiced newborns Monitoring of bilirubin in newborns on therapy for hyperbilirubinaemia |
| Data | Number of true positives and false positives Number of true negatives and false negatives Number of undetermined/uninterpretable results Sensitivity and specificity of index test Number of missing results for index test Number of missing results for reference standard |
| Notes | Source of funding (whether any author is affiliated with the manufacturer of the index test; the study was directly funded by the manufacturer; authors reported conflicts of interests related to the manufacturer or other funding sources) |
