Symptoms, ultrasound imaging and biochemical markers alone or in combination for the diagnosis of ovarian cancer in women with symptoms suspicious of ovarian cancer
Appendices
Appendix 1. Search strategy
MEDLINE search strategy
1. Symptoms scores
Search strategy
Database: Ovid MEDLINE(R) 1946 to April Week 2 2015
1 exp ovarian neoplasms/di
2 exp adnexal diseases/di
3 ((ovar$ or adnexal or fallopian or peritoneal$ or pelvic) adj3 (cancer$ or carcinoma$ or malignan$ or mass or masses or cyst or cysts or neoplas$ or tumor$ or tumour$)).tw.
4 ((borderline or border line) adj4 ovar$).tw.
5 exp Fallopian Tube Neoplasms/di
6 exp Peritoneal Neoplasms/di
7 exp pelvic neoplasms/di
8 ((epithelial or germ cell) adj5 ovar$).tw.
9 or/1‐8
10 exp "Signs and Symptoms"/
11 symptom$.ti,ab.
12 exp early diagnosis/ or exp Diagnosis/
13 exp "Early Detection of Cancer"/
14 (early adj (sign$ or symptom$)).tw.
15 (abdom$ adj3 (pressure or pain$ or swelling$ or hard)).tw.
16 (bowel irregularit$ or bloat$ or fullness or satiet$ or gastro$).tw.
17 (fatigue or weight loss$ or weight gain$ or constipat$ or diarrhoea or diarrhea or gas).tw.
18 (nausea$ or indigestion).tw.
19 ((loss or lack) adj3 (energ$ or appetite$)).tw.
20 (urin$ adj3 (frequenc$ or urgenc$)).tw.
21 ((leg$ or ankle$) adj2 (swell$ or swollen)).tw.
22 ((abnormal or irregular or postmenopausal) adj1 vaginal adj (bleed$ or discharge$)).tw.
23 (pelvic discomfort$ or pelvic pain$ or chest pain$ or respirator$ difficult$ or lower back
pain$).tw.
24 or/10‐22
25 9 and 24
26 (index or risk$ or score$ or scoring or checklist$ or rule$ or indices or tool$ or instrument$ or survey$ or questionnaire$ or interview$).tw.
27 25 and 26
28 limit 27 to (humans and yr="2009 ‐ 2015")
2. Biomarkers
Search strategy
Database: Ovid MEDLINE(R) 1946 to April Week 3 2015
1 exp Ovarian Neoplasms/di
2 exp Adnexal Diseases/di
3 ((ovar$ or adnexal or fallopian or peritoneal$ or pelvic) adj3 (cancer$ or carcinoma$ or malignan$ or mass or masses or cyst or cysts or neoplas$ or tumour$ or tumor$)).tw.
4 ((borderline or border line) adj4 ovar$).tw.
5 exp Fallopian Tube Neoplasms/di
6 exp Peritoneal Neoplasms/di
7 exp Pelvic Neoplasms/di
8 ((epithelial or germ cell) adj5 ovar$).tw.
9 or/1‐8
10 exp Tumor Markers, Biological/
11 exp Biological Markers/
12 Proteomics/
13 Genetic Markers/
14 Metabolomics/
15 multiplex$.tw.
16 multivariate.tw.
17 (CA125 or CA‐125 or HE4 or OVA 1 or OVA1 or HCG or LDH or AFP or CEA).tw.
18 CA‐125 Antigen/
19 Chorionic Gonadotropin/
20 L‐Lactate Dehydrogenase/
21 alpha‐Fetoproteins/
22 Carcinoembryonic Antigen/
23 or/10‐22
24 9 and 23
25 limit 24 to (humans and yr="2009‐2015")
3. Ultrasound/IOTA
Search strategy
Database: Ovid MEDLINE(R) 1946 to April Week 3 2015
1 exp Ovarian Neoplasms/di
2 exp Adnexal Diseases/di
3 ((borderline or border line) adj4 ovar$).tw.
4 exp Fallopian Tube Neoplasms/di
5 exp Peritoneal Neoplasms/di
6 exp Pelvic Neoplasms/di
7 ((ovar$ or adnexal or fallopian or peritoneal$ or pelvic) adj3 (cancer$ or carcinoma$ or malignan$ or mass or masses or cyst or cysts or neoplas$ or tumour$ or tumor$)).tw.
8 ((epithelial or germ cell) adj5 ovar$).tw.
9 or/1‐8
10 exp ultrasonography/
11 ultraso$.tw.
12 (transvagina$ adj2 sonogra$).tw.
13 or/10‐12
14 9 and 13
15 limit 14 to (human and yr=2009‐2015)
16 IOTA.tw.
17 International Ovarian Tumor Analysis.tw.
18 ((ovarian or epithelial or adnex$ or fallopian or peritoneal or pelvic) adj3 (model$ or regress$ or rule$ or score$ or algorithm$ or term$ or definition$ or measure$)).ti,ab.
19 or/16‐18
20 13 and 19
21 limit 20 to human
22 15 or 21
Appendix 2. Data extraction form
Data extraction: ROCkeTS
| Please enter your initials (NR, RC) |
STUDY IDENTIFICATION AND STUDY TYPE
| Study ID (number allocated in included studies PDFs and 'notes' field in reference manager) | Comments | |
| Study authors (surname and year) | ||
| Country in which study conducted | ||
| Study design Please choose from: ‐ 'Prospective' cross‐sectional test accuracy study (P CS) ‐ 'Retrospective' cross‐sectional test accuracy study (R CS) ‐ Case‐control test accuracy study (CC) ‐ Comparison of the accuracy of tests or testing strategies in 2 different populations (e.g. a randomised trial of tests or testing strategies) (Between‐person comparison ‐ BPC) ‐ Within‐person comparison of test accuracy (WPC) ‐ Unclear(U) |
PATIENT SELECTION DETAIL
For studies comparing two index tests or testing strategies in different patient populations complete details for each patient population (copy and paste table if necessary)
| FOR NON‐COMPARATIVE STUDIES OR WITHIN‐PERSON TEST COMPARISONS (WPC) assessing the accuracy of one index test or one index testing strategy describe methods of participant selection as reported (cut and paste from paper if possible) Include total number of study participants | Comments | |
| FOR BETWEEN‐PERSON COMPARATIVE STUDIES (BPC) of two index tests or testing strategies in different patient populations describe methods of participant selection receiving each index test or testing strategy as reported (cut and paste from paper if possible) Include total number of study participants receiving each test or testing strategy | ||
| Clinical setting mentioned If yes | Y/N/U Primary/community Secondary/hospital/cancer unit/cancer centre NR | |
| Risk factors such as age, menopause, family history, BRCA status, other cancers mentioned in the study |
INCLUDED PATIENT CHARACTERISTICS DETAIL.
For studies comparing two index tests or testing strategies in different patient populations complete details for each patient population (copy and paste table if necessary)
| FOR NON‐COMPARATIVE STUDIES OR WITHIN‐PERSON TEST COMPARISONS (WPC) describe characteristics of included patients as reported (cut and paste from paper if possible) | Comments | |
| FOR BETWEEN‐PERSON COMPARATIVE STUDIES (BPC) of two index tests or testing strategies in different patient populations describe characteristics of participants receiving each index test or testing strategy as reported (cut and paste from paper if possible) | ||
| Age as reported or not reported ('NR') (delete options as necessary) | ‐ Age range: ‐ Age mean (SD): ‐ NR | |
| Menopausal status(n/%) | pre | post |
| Prior test(s) | Symptoms Signs Biomarker/s USS NR | |
| Histology | Number (%) | |
| Benign | Number (%) | |
| Endometriosis | ||
| Others | ||
| Tumours of low malignant potential (LMP/borderline) | Number (%) | |
| Malignant | Number (%) | |
| I | Number (%) | |
| II | Number (%) | |
| III | Number (%) | |
| IV | Number (%) | |
PATIENT SELECTION RISK OF BIAS
| PATIENT SELECTION A. Risk of bias | |
| Describe methods of patient selection: | |
| a) Was a consecutive or random sample of patients enrolled? | Yes/No/Unclear |
| b) Was a case‐control design avoided? | Yes/No/Unclear |
| c) Did the study avoid inappropriate exclusions? a) include all ages and regardless of menopausal status or justify restrictions b) include all stages of ovarian cancer. c) include co‐morbidities such as infertility and endometriosis | Yes/No/Unclear |
| Could the selection of patients have introduced bias? If a) and b) and c) 'YES' = low risk of bias If a) or b)or c) 'No' = high risk of bias If a) or b)or c) 'Unclear' = unclear risk of bias | RISK: LOW/HIGH/UNCLEAR |
| B. Concerns regarding applicability | |
| Describe included patients (prior testing, presentation, intended use of index test and setting): | |
| Is there concern that the included patients do not match the review question? a) Patients all symptomatic OR symptomatic and asymptomatic can be disaggregated b) Prior tests primary care: self reported symptoms c) Prior tests secondary care: self reported symptoms OR self reported symptoms PLUS one or more of biochemical markers and ultrasound | CONCERN: LOW/HIGH/UNCLEAR Low ‐ a) and b) and C) Yes High ‐ a) or b) or C) No Unclear ‐ a) or b) or C) Unclear |
INDEX TEST(S) DETAILS
For studies comparing two index tests or testing strategies in different patient populations complete details for each index test or testing strategy (copy and paste table if necessary)
| INDEX TEST(S) | Test (note the type of symptom, biomarker, ultrasound variable) | Test threshold (what constitutes abnormal test symptoms, signs, biomarkers or USS: threshold value or fixed value of abnormality | Threshold value or fixed value of abnormality | Clinical setting in which index test performed | If operator was blinded to previous test (s) result | Describe what prior tests information was available to those interpreting index test | Comments Detail about conduct of index test that might be a source of heterogeneity (e.g. experience of operator (ultrasound, symptoms), type of technology (biomarkers)) ‐ For test combinations test order and rule for combining tests | |
| Symptoms (list) | Yes No NR | (Number of symptoms and time element) | Primary/community/family practice Secondary: hospital/cancer unit/cancer centre/gyn oncologist NR/U/Mixed | Yes No NR | ||||
| Signs | Yes No NR | Primary/community/family practice Secondary: hospital/cancer unit/cancer centre/gyn oncologist NR/U/Mixed | Yes No NR | |||||
| Biomarkers | Yes No NR | Primary/community/family practice Secondary: hospital/cancer unit/cancer centre/gyn oncologist NR/U/Mixed | Yes No NR | |||||
| USS | Yes No NR | Primary/community/family practice Secondary: hospital/cancer unit/cancer centre/gyn oncologist NR/U/Mixed | Yes No NR | |||||
| Combination | Yes No NR | Primary/community/family practice Secondary: hospital/cancer unit/cancer centre/gyn oncologist NR/U/Mixed | Yes No NR | |||||
| If a combination of tests (a testing strategy) was used for each participant please detail: ‐ What combination of tests? ‐ The order in which tests were performed? ‐ The rule for combining test results: E.g. + and + = surgery E.g. + and ‐ = surgery E.g. + and ‐ = no surgery E.g. – and ‐ = no surgery Etc or not reported ('NR') | Combination: Order: Rule for combining tests: | Comments |
INDEX TEST(S)
(If more than one index test was used, please complete for each test).
| A1. Risk of bias (symptoms) | |
| Describe the index test and how it was conducted and interpreted: | |
| a) Was the index test or testing strategy result interpreted without knowledge of the results of the reference standard? | Yes/No/Unclear |
| b) If a threshold was used, was it pre‐specified? | Yes/No/Unclear |
| Could the conduct or interpretation of the index test have introduced bias? | RISK: LOW/HIGH/UNCLEAR High ‐ a) or b) No Low‐ a) and b) Yes Unclear ‐ a) or b) Unclear |
| A2. Risk of bias (ultrasound) | |
| Describe the index test and how it was conducted and interpreted: | |
| a) Was the index test or testing strategy result interpreted without knowledge of the results of the reference standard? | Yes/No/Unclear |
| b) If a threshold was used, was it pre‐specified? | Yes/No/Unclear |
| Could the conduct or interpretation of the index test have introduced bias? | RISK: LOW/HIGH/UNCLEAR High ‐ a) or b) No Low ‐ a) and b) Yes Unclear ‐ a) or b) Unclear |
| A3. Risk of bias (Biomarkers) rule different because objective test in comparison to US and symptom elicitation | |
| Describe the index test and how it was conducted and interpreted: | |
| a) Was the index test or testing strategy result interpreted without knowledge of the results of the reference standard? | Yes/No/Unclear |
| b) If a threshold was used, was it pre‐specified? | Yes/No/Unclear |
| Could the conduct or interpretation of the index test have introduced bias? | RISK: LOW/HIGH/UNCLEAR High ‐ b) No or (a) and b)) No Low ‐ a) and b) Yes Unclear ‐ a) or b) Unclear |
| A4. Risk of bias (within‐study combination) | |
| Describe the index test and how it was conducted and interpreted: | |
| a) Was the index test or testing strategy result interpreted without knowledge of the results of the reference standard? | Yes/No/Unclear |
| b) If a threshold was used, was it pre‐specified? | Yes/No/Unclear |
| c) i) Were symptoms/signs interpreted without knowledge of ultrasound or biomarkers; ii) was ultrasound interpreted without knowledge of biomarkers | Yes/No/Unclear |
| Could the conduct or interpretation of the index test have introduced bias? | RISK: LOW/HIGH/UNCLEAR High ‐ a) or b) or c) No Low ‐ a) and b) or c)Yes Unclear ‐ a) or b) or c) Unclear |
| B. Concerns regarding applicability | |
| a) Is the skill of person performing US and eliciting symptoms detailed? (level of training and/or experience) | Yes/No/Unclear/NA |
| b) Was US performed in all patients by non‐specialised sonographers | Yes/No/Unclear |
| c) Was US performed with knowledge of symptoms/signs/biomarkers | Yes/No/Unclear |
| Is there concern that the index test, its conduct or interpretation differ from the review question? | CONCERN: LOW/HIGH/UNCLEAR High ‐ a) or b) or C) No Low ‐ a) and b) or c)Yes Unclear ‐ a) or b) Unclear |
REFERENCE STANDARD AND TARGET CONDITION DETAIL
| REFERENCE STANDARD Surgery (%) F ollow‐up (%) and length of follow‐up |
TARGET CONDITION
| TARGET CONDITION Target conditions are ovarian cancer (see list of different histology of ovarian cancer) | Epithelial ovarian cancer (EOC) | Number (%) | Comments |
| Serous | |||
| Mucinous | |||
| Endometrioid | |||
| Clear | |||
| Germ cell tumours | |||
| Stromal cell tumours | |||
| LMP | |||
| Others (metastasis) |
REFERENCE STANDARD RISK OF BIAS
| A. Risk of bias | |
| Describe the reference standard and how it was conducted and interpreted: | |
| a) Is the reference standard likely to correctly classify the target condition? Index test +ve: Histology following laparoscopy or laparotomy | Yes/No/Unclear |
| b) Is the reference standard likely to correctly classify the target condition? Index test –ve: Yes ‐ if a minimum follow‐up period of greater than 12 months is included as required to assess whether the target condition is present No ‐ if a minimum 12‐month follow‐up period is absent Unclear ‐ if no information on follow‐up period is included | Yes/No/Unclear |
| Could the reference standard, its conduct or its interpretation have introduced bias | RISK: LOW/HIGH/UNCLEAR High ‐ a) or b) No Low ‐ a) and b) Yes Unclear ‐ a) or b) Unclear |
DOMAIN 3: REFERENCE STANDARD (continued)
| B. Concerns regarding applicability | |
| Is there concern that the target condition as defined by the reference standard does not match the review question? Yes ‐ ovarian cancer, borderline and metastatic disease are not differentiated (and cannot be for analysis) No ‐ ovarian cancer, borderline and metastatic disease can be differentiated for analysis Unclear ‐ unclear if ovarian cancer, borderline and metastatic disease have been disaggregated | CONCERN: Yes/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 2 x 2 table (refer to study flow diagram): Describe the time interval and any interventions between index test(s) and reference standard: | |
| a) Was there less than 3 months interval between application of each index test and application of the reference standard? | Yes/No/Unclear |
| b) Did all patients receive a reference standard? | Yes/No/Unclear |
| c) Did all index test ‐ve patients receive the same reference standard? | Yes/No/Unclear |
| d) Were all patients who underwent testing included in the analysis? | Yes/No/Unclear |
| Could the conduct or interpretation of reference standard have introduced bias? | RISK: LOW/HIGH/UNCLEAR LOW ‐ a) and b) and c) and d) ‐ Yes HIGH ‐ a) and b) and c) and d) ‐ No UNCLEAR ‐ a) and b) and c) and d) ‐ Unclear |
COMPARATIVE DOMAIN (if applicable)
| A. Risk of bias | |
| Describe the selection process for participants to receive one or other index test or index testing strategy Describe the time interval and any interventions between index test(s) for within‐person test comparisons | |
| a) For studies comparing two or more index tests or testing strategies in different patient populations were the selection criteria for participants receiving one or other index test or testing strategy the same? | Yes/No/Unclear/NA |
| b) For within‐study comparisons of index tests: ‐ was the interval between application of each index test < 3 months | Yes/No/Unclear/NA |
| c) For within‐study comparisons of individual index tests: ‐ were index tests interpreted blind to the results of other index test results | Yes/No/Unclear/NA |
| Could the conduct of the comparative study have introduced bias? LOW ‐ a) OR (b) and c)) ‐ Yes HIGH ‐ a) OR (b) and c)) ‐ No UNCLEAR ‐ a) OR (b) or c)) ‐ Unclear | RISK: LOW/HIGH/UNCLEAR |
| B. Concerns regarding applicability | |
| Describe included patients (prior testing, presentation, intended use of index test and setting): | |
| Is there concern that included patients have been selected in a different way to participants in non‐comparative studies Low ‐ No High ‐ Yes Unclear ‐ Unclear | CONCERN: LOW/HIGH/UNCLEAR |
RISK OF BIAS FOR MULTIVARIABLE DIAGNOSTIC MODELLING STUDIES (if applicable)
| 1. Participant selection | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| a) Were appropriate data sources used, e.g. cohort, RCT or nested case‐control study data? | DEV | Yes/No/Unclear | ||
| b) Were participants enrolled at a similar state of health, or were predictors considered to account for differences? | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| Could the selection of patients have introduced bias? HIGH: a) OR a) and b) ‐ YES LOW: a) OR a) and b) ‐ NO UNCLEAR: a) OR a) and b) ‐ UNCLEAR | HIGH/LOW/ UNCLEAR | HIGH/LOW/ UNCLEAR | ||
| 3. Predictors | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| a) Were predictors defined and assessed in a similar way for all participants? | DEV | Yes/No/Unclear | ||
| b) Are all predictors available at the time the model is intended to be used | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| c) Were all relevant predictors analysed?: No if symptoms only; No if US index test only; No if combination of index tests (symptoms, US and biomarkers) but miss out US OR Symptom OR FDA approved biomarkers | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| Could the definition, measurement or analysis of predictors introduced bias? HIGH: a) OR b) OR c) ‐ YES LOW: a) OR b) OR c) ‐ NO UNCLEAR: a) OR b) OR c) ‐ UNCLEAR | DEV | HIGH/LOW/ UNCLEAR | VAL | HIGH/LOW/ UNCLEAR |
| 3. ANALYSIS | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| a) Were there a reasonable number of outcome events? | DEV | Yes/No/Unclear | ||
| b) Were there a reasonable number of outcome events? | VAL | Yes/No/Unclear | ||
| c) Were non‐binary predictors handled appropriately? | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| d) Was selection of predictors based on univariable analysis avoided? | DEV | Yes/No/Unclear | ||
| e) Do predictors and their assigned weights in the final model correspond to the results from multivariable analysis? | DEV | Yes/No/Unclear | ||
| f) For the model or any simplified score, were relevant performance measures evaluated, e.g. calibration, discrimination, (re)classification and net benefit? | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| g) Was the model recalibrated or was it likely (based on the evidence presented, e.g. calibration plot) that recalibration was not needed? | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| h) Was model validation undertaken in individuals other than those in the model development (external validation)? | VAL | Yes/No/Unclear | ||
| Could the analysis strategy have introduced bias? HIGH: a) OR b) OR c) OR d) OR e) OR f) OR g) OR h) ‐ YES LOW: a) OR b) OR c) OR d) OR e) OR f) OR g) OR h) ‐ NO UNCLEAR: a) OR b) OR c) OR d) OR e) OR f) OR g) OR h) ‐ UNCLEAR | DEV | HIGH/LOW/ UNCLEAR | VAL | HIGH/LOW/ UNCLEAR |
TEST ACCURACY DATA
If reported please complete the following 2 x 2 contingency table. For studies investigating the accuracy of more than one index test or testing strategy please complete a 2 x 2 table for each test/testing strategy (cut and paste table as necessary). Imaging test results will be dichotomous.
LOWEST LEVEL OF AGGREGATION:
Fill in data as available.
| REFERENCE STANDARD (ovarian cancer) | REFERENCE STANDARD (borderline) | REFERENCE STANDARD (benign) | ||
| INDEX TEST/TESTING STRATEGY +ve for ovarian cancer | TOTAL INDEX TEST +ve | |||
| INDEX TEST/TESTING STRATEGY +ve for borderline | TOTAL INDEX TEST +ve | |||
| INDEX TEST/TESTING STRATEGY +ve for benign | TOTAL INDEX TEST ‐ve | |||
| DISEASE +ve | TOTAL borderline | DISEASE ‐ve | TOTAL 'N' | |
| Aggregation borderline +ve | TOTAL DISEASE +ve | TOTAL DISEASE ‐ve | TOTAL 'N' | |
| Aggregation borderline ‐ve | TOTAL DISEASE +ve | TOTAL DISEASE ‐ve | TOTAL 'N' | |
INSERT ANOTHER MORE DETAILED TABLE WITH SUB‐CATEGORIES OF OVARIAN CANCER FOR LOW GRADE AND HIGH GRADE, TYPE 1 AND TYPE 2, EARLY‐STAGE AND LATE‐STAGE
| REFERENCE STANDARD (early‐stage) | REFERENCE STANDARD (advanced‐stage) | ||
| INDEX TEST/TESTING STRATEGY +ve (early‐stage) | TOTAL INDEX TEST +ve | ||
| INDEX TEST/TESTING STRATEGY +ve (late‐stage) | TOTAL INDEX TEST ‐ve | ||
| DISEASE +ve | DISEASE ‐ve | TOTAL 'N' |
| REFERENCE STANDARD (Type 1) | REFERENCE STANDARD (Type 2) | ||
| INDEX TEST/TESTING STRATEGY +ve (Type 1) | TOTAL INDEX TEST +ve | ||
| INDEX TEST/TESTING STRATEGY +ve (Type 2) | TOTAL INDEX TEST ‐ve | ||
| DISEASE +ve | DISEASE ‐ve | TOTAL 'N' |
Appendix 3. QUADAS‐2
PATIENT SELECTION RISK OF BIAS
| PATIENT SELECTION A. Risk of bias | |
| Describe methods of patient selection: | |
| a) Was a consecutive or random sample of patients enrolled? | Yes/No/Unclear |
| b) Was a case‐control design avoided? | Yes/No/Unclear |
| c) Did the study avoid inappropriate exclusions? a) include all ages and regardless of menopausal status or justify restrictions b) include all stages of ovarian cancer c) include co‐morbidities such as infertility and endometriosis | Yes/No/Unclear |
| Could the selection of patients have introduced bias? If a) and b) and c) 'YES'= low risk of bias If a) or b) or c) 'No' = high risk of bias If a) or b) or c) 'Unclear'= unclear risk of bias | RISK: LOW/HIGH/UNCLEAR |
| B. Concerns regarding applicability | |
| Describe included patients (prior testing, presentation, intended use of index test and setting): | |
| Is there concern that the included patients do not match the review question? a) Patients all symptomatic OR symptomatic and asymptomatic can be disaggregated b) Prior tests primary care: self reported symptoms c) Prior tests secondary care: self reported symptoms OR self reported symptoms PLUS one or more of biochemical markers and ultrasound | CONCERN: LOW/HIGH/UNCLEAR Low ‐ a) and b) and C) Yes High ‐ a) or b) or C) No Unclear ‐ a) or b) or C) Unclear |
INDEX TEST(S)
(If more than one index test was used, please complete for each test).
| A1. Risk of bias (symptoms) | |
| Describe the index test and how it was conducted and interpreted: | |
| a) Was the index test or testing strategy result interpreted without knowledge of the results of the reference standard? | Yes/No/Unclear |
| b) If a threshold was used, was it pre‐specified? | Yes/No/Unclear |
| Could the conduct or interpretation of the index test have introduced bias? | RISK: LOW/HIGH/UNCLEAR High ‐ a) or b) No Low ‐ a) and b) Yes Unclear ‐ a) or b) Unclear |
| A2. Risk of bias (ultrasound) Describe the index test and how it was conducted and interpreted: a) Was the index test or testing strategy result interpreted without knowledge of the results of the reference standard? Yes/No/Unclear b) If a threshold was used, was it pre‐specified? Yes/No/Unclear Could the conduct or interpretation of the index test have introduced bias? RISK: LOW/HIGH/UNCLEAR High ‐ a) or b) No Low ‐ a) and b) Yes Unclear ‐ a) or b) Unclear A3. Risk of bias (biomarkers) rule different because objective test in comparison to US and symptom elicitation | |
| Describe the index test and how it was conducted and interpreted: | |
| a) Was the index test or testing strategy result interpreted without knowledge of the results of the reference standard? | Yes/No/Unclear |
| b) If a threshold was used, was it pre‐specified? | Yes/No/Unclear |
| Could the conduct or interpretation of the index test have introduced bias? | RISK: LOW/HIGH/UNCLEAR High ‐ a) or b) No Low ‐ a) and b) Yes Unclear ‐ a) or b) Unclear |
| B. Concerns regarding applicability | |
| a) Is the skill of person performing US and eliciting symptoms detailed? (level of training and/or experience) | Yes/No/Unclear/NA |
| b) Was US performed in all patients by non‐specialised sonographers | Yes/No/Unclear |
| c) Was US performed with knowledge of symptoms/signs/biomarkers | Yes/No/Unclear |
| Is there concern that the index test, its conduct or interpretation differ from the review question? | CONCERN: LOW/HIGH/UNCLEAR High ‐ a) or b) or C)No Low ‐ a) and b) or c)Yes Unclear ‐ a) or b) Unclear |
REFERENCE STANDARD RISK OF BIAS
| A. Risk of bias | |
| Describe the reference standard and how it was conducted and interpreted: | |
| a) Is the reference standard likely to correctly classify the target condition? Index test +ve: Histology following laparoscopy or laparotomy | Yes/No/Unclear |
| b) Is the reference standard likely to correctly classify the target condition? Index test –ve: Yes ‐ if a minimum follow‐up period of greater than 12 months is included as required to assess whether the target condition is present No ‐ if a minimum 12‐month follow‐up period is absent Unclear ‐ if no information on follow‐up period is included | Yes/No/Unclear |
| Could the reference standard, its conduct or its interpretation have introduced bias | RISK: LOW/HIGH/UNCLEAR High ‐ a) or b) No Low ‐ a) and b) Yes Unclear ‐ a) or b) Unclear |
DOMAIN 3: REFERENCE STANDARD (continued)
| B. Concerns regarding applicability | |
| Is there concern that the target condition as defined by the reference standard does not match the review question? Yes ‐ ovarian cancer, borderline and metastatic disease are not differentiated (and cannot be for analysis) No ‐ ovarian cancer, borderline and metastatic disease can be differentiated for analysis Unclear ‐ unclear if ovarian cancer, borderline and metastatic disease have been disaggregated | CONCERN: Yes/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 2 x 2 table (refer to study flow diagram): Describe the time interval and any interventions between index test(s) and reference standard: | |
| a) Was there less than 3 months interval between application of each index test and application of the reference standard? | Yes/No/Unclear |
| b) Did all patients receive a reference standard? | Yes/No/Unclear |
| c) Did all index test ‐ve patients receive the same reference standard? | Yes/No/Unclear |
| d) Were all patients who underwent testing included in the analysis? | Yes/No/Unclear |
| Could the conduct or interpretation of reference standard have introduced bias? | RISK: LOW/HIGH/UNCLEAR LOW ‐ a) and b) and c) and d) ‐ Yes HIGH ‐ a) and b) and c) and d) ‐ No UNCLEAR ‐ a) and b) and c) and d) ‐ Unclear |
COMPARATIVE DOMAIN (if applicable)
| A. Risk of bias | |
| Describe the selection process for participants to receive one or other index test or index testing strategy Describe the time interval and any interventions between index test(s) for within‐person test comparisons | |
| a) For studies comparing two or more index tests or testing strategies in different patient populations were the selection criteria for participants receiving one or other index test or testing strategy the same? | Yes/No/Unclear/NA |
| b) For within‐study comparisons of index tests: ‐ was the interval between application of each index test < 3 months | Yes/No/Unclear/NA |
| c) For within‐study comparisons of individual index tests: ‐ were index tests interpreted blind to the results of other index test results | Yes/No/Unclear/NA |
| Could the conduct of the comparative study have introduced bias? LOW ‐ a) OR (b) and c))‐ Yes HIGH ‐ a) OR (b) and c)) ‐ No UNCLEAR ‐ a) OR (b) or c)) ‐ Unclear | RISK: LOW/HIGH/UNCLEAR |
| B. Concerns regarding applicability | |
| Describe included patients (prior testing, presentation, intended use of index test and setting): | |
| Is there concern that included patients have been selected in a different way to participants in non‐comparative studies Low ‐ No High ‐ Yes Unclear ‐ Unclear | CONCERN: LOW/HIGH/UNCLEAR |
RISK OF BIAS FOR MULTIVARIABLE DIAGNOSTIC MODELLING STUDIES (if applicable)
| 1. Participant selection | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| a) Were appropriate data sources used, e.g. cohort, RCT or nested case‐control study data? | DEV | Yes/No/Unclear | ||
| b) Were participants enrolled at a similar state of health, or were predictors considered to account for differences? | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| Could the selection of patients have introduced bias? HIGH: a) OR a) and b) ‐ YES LOW: a) OR a) and b) ‐ NO UNCLEAR: a) OR a) and b) ‐ UNCLEAR | HIGH/LOW/ UNCLEAR | HIGH/LOW/ UNCLEAR | ||
| 3. Predictors | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| a) Were predictors defined and assessed in a similar way for all participants? | DEV | Yes/No/Unclear | ||
| b) Are all predictors available at the time the model is intended to be used | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| c) Were all relevant predictors analysed?: No if symptoms only; No if US index test only; No if combination of index tests (symptoms, US and biomarkers) but miss out US OR Symptom OR FDA approved biomarkers | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| Could the definition, measurement or analysis of predictors introduced bias? HIGH: a) OR b) OR c) ‐ YES LOW: a) OR b) OR c) ‐ NO UNCLEAR: a) OR b) OR c) ‐ UNCLEAR | DEV | HIGH/LOW/ UNCLEAR | VAL | HIGH/LOW/ UNCLEAR |
| 3. ANALYSIS | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| a) Were there a reasonable number of outcome events? | DEV | Yes/No/Unclear | ||
| b) Were there a reasonable number of outcome events? | VAL | Yes/No/Unclear | ||
| c) Were non‐binary predictors handled appropriately? | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| d) Was selection of predictors based on univariable analysis avoided? | DEV | Yes/No/Unclear | ||
| e) Do predictors and their assigned weights in the final model correspond to the results from multivariable analysis? | DEV | Yes/No/Unclear | ||
| f) For the model or any simplified score, were relevant performance measures evaluated, e.g. calibration, discrimination, (re)classification and net benefit? | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| g) Was the model recalibrated or was it likely (based on the evidence presented, e.g. calibration plot) that recalibration was not needed? | DEV | Yes/No/Unclear | VAL | Yes/No/Unclear |
| h) Was model validation undertaken in individuals other than those in the model development (external validation)? | VAL | Yes/No/Unclear | ||
| Could the analysis strategy have introduced bias? HIGH: a) OR b) OR c) OR d) OR e) OR f) OR g) OR h) ‐ YES LOW: a) OR b) OR c) OR d) OR e) OR f) OR g) OR h) ‐ NO UNCLEAR: a) OR b) OR c) OR d) OR e) OR f) OR g) OR h) ‐ UNCLEAR | DEV | HIGH/LOW/ UNCLEAR | VAL | HIGH/LOW/ UNCLEAR |
TEST ACCURACY DATA
If reported please complete the following 2 x 2 contingency table. For studies investigating the accuracy of more than one index test or testing strategy please complete a 2 x 2 table for each test/testing strategy (cut and paste table as necessary). Imaging test results will be dichotomous.
LOWEST LEVEL OF AGGREGATION:
Fill in data as available.
| REFERENCE STANDARD (ovarian cancer) | REFERENCE STANDARD (borderline) | REFERENCE STANDARD (benign) | ||
| INDEX TEST/TESTING STRATEGY +ve for ovarian cancer | TOTAL INDEX TEST +ve | |||
| INDEX TEST/TESTING STRATEGY +ve for borderline | TOTAL INDEX TEST +ve | |||
| INDEX TEST/TESTING STRATEGY +ve for benign | TOTAL INDEX TEST ‐ve | |||
| DISEASE +ve | TOTAL borderline | DISEASE ‐ve | TOTAL 'N' | |
| Aggregation borderline +ve | TOTAL DISEASE +ve | TOTAL DISEASE ‐ve | TOTAL 'N' | |
| Aggregation borderline ‐ve | TOTAL DISEASE +ve | TOTAL DISEASE ‐ve | TOTAL 'N' | |
INSERT ANOTHER MORE DETAILED TABLE WITH SUB‐CATEGORIES OF OVARIAN CANCER FOR TYPE 1 AND TYPE 2
| REFERENCE STANDARD (early‐stage) | REFERENCE STANDARD (advanced‐stage) | ||
| INDEX TEST/TESTING STRATEGY +ve (early‐stage) | TOTAL INDEX TEST +ve | ||
| INDEX TEST/TESTING STRATEGY +ve (late‐stage) | TOTAL INDEX TEST ‐ve | ||
| DISEASE +ve | DISEASE ‐ve | TOTAL 'N' |
| REFERENCE STANDARD (Type 1) | REFERENCE STANDARD (Type 2) | ||
| INDEX TEST/TESTING STRATEGY +ve (Type 1) | TOTAL INDEX TEST +ve | ||
| INDEX TEST/TESTING STRATEGY +ve (Type 2) | TOTAL INDEX TEST ‐ve | ||
| DISEASE +ve | DISEASE ‐ve | TOTAL 'N' |
