title: The clinical performance of the M4 decision support model to triage women with a pregnancy of unknown location as at low or high risk of complications.
abstract: What are the adverse outcomes associated with using the M4 model in everyday clinical practice for women with pregnancy of unknown location (PUL)?
  
  
  
  There were 17/835 (2.0%) adverse events and no serious adverse events associated with the performance of the M4 model in clinical practice.
  
  
  
  The M4 model has previously been shown to stratify women classified as a PUL as at low or high risk of complications with a good level of test performance. The triage performance of the M4 model is better than single measurements of serum progesterone or the hCG ratio (serum hCG at 48 h/hCG at presentation).
  
  
  
  A prospective multi-centre cohort study of 1022 women with a PUL carried out between August 2012 and December 2013 across 2 university teaching hospitals and 1 district general hospital.
  
  
  
  All women presenting with a PUL to the early pregnancy units of the three hospitals were recruited. The final outcome for PUL was either a failed PUL (FPUL), intrauterine pregnancy (IUP) or ectopic pregnancy (EP) (including persistent PUL (PPUL)), with EP and PPUL considered high-risk PUL. Their hCG results at 0 and 48 h were entered into the M4 model algorithm. If the risk of EP was ≥5%, the PUL was predicted to be high-risk and the participant was asked to re-attend 48 h later for a repeat hCG and transvaginal ultrasound scan by a senior clinician. If the PUL was classified as 'low risk, likely failed PUL', the participant was asked to perform a urinary pregnancy test 2 weeks later. If the PUL was classified as 'low risk, likely intrauterine', the participant was scheduled for a repeat scan in 1 week. Deviations from the management protocol were recorded as either an 'unscheduled visit (participant reason)', 'unscheduled visit (clinician reason)' or 'differences in timing (blood test/ultrasound)'. Adverse events were assessed using definitions outlined in the UK Good Clinical Practice Guidelines' document.
  
  
  
  A total of 835 (82%) women classified as a PUL were managed according to the M4 model (9 met the exclusion criteria, 69 were lost to follow-up, 109 had no hCG result at 48 h). Of these, 443 (53%) had a final outcome of FPUL, 298 (36%) an IUP and 94 (11%) an EP. The M4 model predicted 70% (585/835) PUL as low risk, of which 568 (97%) were confirmed as FPUL or IUP. Of the 17 EP and PPUL misclassified as low risk, 5 had expectant management, 7 medical management with methotrexate and 5 surgical intervention.Nineteen PUL had an unscheduled visit (participant reason), 38 PUL had an unscheduled visit (clinician reason) and 68 PUL had deviations from protocol due to a difference in timing (blood test/ultrasound).Adverse events were reported in 26 PUL and 1 participant had a serious adverse event. A total of 17/26 (65%) adverse events were misclassifications of a high risk PUL as low risk by the M4 model, while 5/26 (19%) adverse events were related to incorrect clinical decisions. Four of the 26 adverse events (15%) were secondary to unscheduled admissions for pain/bleeding. The serious adverse event was due to an incorrect clinical decision.
  
  
  
  A limitation of the study was that 69/1022 (7%) of PUL were lost to follow-up. A 48 h hCG level was missing for 109/1022 (11%) participants.
  
  
  
  The low number of adverse events (2.0%) suggests that expectant management of PUL using the M4 prediction model is safe. The model is an effective way of triaging women with a PUL as being at high- and low-risk of complications and rationalizing follow-up. The multi-centre design of the study is more likely to make the performance of the M4 model generalizable in other populations.
  
  
  
  None.
  
  
  
  Not applicable.
authors.affiliation: Tommy's National Early Miscarriage Research Centre, Queen Charlottes & Chelsea Hospital, Imperial College, Du Cane Road, London W12 0HS, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bobdiwala
authors.affiliation: Tommy's National Early Miscarriage Research Centre, Queen Charlottes & Chelsea Hospital, Imperial College, Du Cane Road, London W12 0HS, UK West Middlesex University Hospital, Twickenham Road, Isleworth, London TW7 6AF, UK.
authors.forename: S
authors.initials: S
authors.lastname: Guha
authors.affiliation: Department of Development and Regeneration, KU Leuven, Herestraat 49 Box 7003, Leuven B-3000, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Van Calster
authors.affiliation: Hillingdon Hospital, Pield Heath Road, Uxbridge UB8 3NN, UK.
authors.forename: F
authors.initials: F
authors.lastname: Ayim
authors.affiliation: Chelsea & Westminster Hospital, 329 Fulham Road, London SW10 9NH, UK.
authors.forename: N
authors.initials: N
authors.lastname: Mitchell-Jones
authors.affiliation: Tommy's National Early Miscarriage Research Centre, Queen Charlottes & Chelsea Hospital, Imperial College, Du Cane Road, London W12 0HS, UK.
authors.forename: M
authors.initials: M
authors.lastname: Al-Memar
authors.affiliation: Hillingdon Hospital, Pield Heath Road, Uxbridge UB8 3NN, UK.
authors.forename: H
authors.initials: H
authors.lastname: Mitchell
authors.affiliation: Tommy's National Early Miscarriage Research Centre, Queen Charlottes & Chelsea Hospital, Imperial College, Du Cane Road, London W12 0HS, UK.
authors.forename: C
authors.initials: C
authors.lastname: Stalder
authors.affiliation: Chelsea & Westminster Hospital, 329 Fulham Road, London SW10 9NH, UK.
authors.forename: C
authors.initials: C
authors.lastname: Bottomley
authors.affiliation: Hillingdon Hospital, Pield Heath Road, Uxbridge UB8 3NN, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kothari
authors.affiliation: Department of Development and Regeneration, KU Leuven, Herestraat 49 Box 7003, Leuven B-3000, Belgium Department of Obstetrics and Gynaecology, University Hospitals Leuven, Campus Gasthuisberg, KU Leuven, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Timmerman
authors.affiliation: Tommy's National Early Miscarriage Research Centre, Queen Charlottes & Chelsea Hospital, Imperial College, Du Cane Road, London W12 0HS, UK Department of Development and Regeneration, KU Leuven, Herestraat 49 Box 7003, Leuven B-3000, Belgium Department of Obstetrics and Gynaecology, University Hospitals Leuven, Campus Gasthuisberg, KU Leuven, Belgium t.bourne@imperial.ac.uk.
authors.forename: T
authors.initials: T
authors.lastname: Bourne
mesh_terms: D000328:Adult; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis* / Q000000981:diagnostic imaging; D011271:Pregnancy, Ectopic / Q000175:diagnosis / Q000000981:diagnostic imaging; D011446:Prospective Studies; D018570:Risk Assessment; D014218:Triage
keywords: adverse events; decision support techniques; ectopic pregnancy; miscarriage; pregnancy of unknown location; triage; ultrasonography