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Quantifying intervals to diagnosis in myeloma: a systematic review and meta-analysis
  1. Constantinos Koshiaris1,
  2. Jason Oke1,
  3. Lucy Abel1,
  4. Brian D Nicholson1,
  5. Karthik Ramasamy2,3,
  6. Ann Van den Bruel1
  1. 1 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  2. 2 Department of Haematology, Oxford University Hospitals NHS Trust, Oxford, UK
  3. 3 National Institute for Health Research (NIHR) Biomedical Research Center Blood Theme, Oxford, UK
  1. Correspondence to Mr Constantinos Koshiaris; constantinos.koshiaris{at}


Objectives To quantify the duration of each step of the diagnostic pathway for patients with multiple myeloma from symptom onset to confirmation of diagnosis.

Design Systematic review and meta-analysis.

Data sources and selection criteria The MEDLINE and Embase databases were searched up until January 2018 to identify articles that reported time intervals from onset of symptoms to diagnosis. Articles focusing on children or adolescents and on the asymptomatic form of the disease (monoclonal gammopathies and smouldering myeloma) were excluded.

Data collection and data analysis Data were extracted independently by two reviewers. Weighted estimates of the median and IQR were calculated. Risk of bias was assessed using the Aarhus checklist.

Main results Nine studies were included. The patient interval (first symptom to first presentation) had a median of 26.3 days (IQR: 1–98, n=465, two studies). Subsequently, the primary care interval (first presentation to first referral) was 21.6 days (IQR: 4.6–55.8, n=326, two studies), the diagnostic interval (first presentation to diagnosis) was 108.6 days (IQR: 33.3–241.7, n=5395, seven studies) and the time to diagnosis (first symptom to diagnosis) interval was 163 days (IQR: 84–306, n=341, one study). No studies reported data for the referral to diagnosis interval.

Conclusion The review demonstrates that there is scope for significant reductions in the time to myeloma diagnosis. At present, many patients experience a diagnostic interval longer than 3 months until diagnosis is confirmed.

Review registration Not available. Protocol available in the appendix.

  • multiple myeloma
  • time to diagnosis
  • early diagnosis
  • primary care
  • systematic review
  • delays

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  • Contributors Six authors contributed to this study: CK, JO, LA, BDN, KR, AVdB. CK designed the study with input from AVdB and JO. All authors were involved in the conduct of the study, interpreting the results and in revising and correcting the manuscript. CK and LA reviewed and extracted the data from articles. CK and JO planned and conducted the analysis. The manuscript drafting was led by CK with the contribution of all authors. All authors read and approved the final version of the manuscript.

  • Funding This manuscript presents work carried out as part of a DPhil scholarship awarded to CK funded by the Primary Care Research Trust, The University of Oxford and NIHR Oxford CLAHRC. AVdB is supported through the National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative Oxford at Oxford Health Foundation Trust (IS_DEC_0812_100).

  • Disclaimer This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The dataset is available on request from the corresponding author.

  • Presented at This study has been presented as an oral presentation at the SAPC Conference, Dublin, July 2016.

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