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. 2015 Nov 11:351:h5441.
doi: 10.1136/bmj.h5441.

Development and validation of risk prediction equations to estimate future risk of blindness and lower limb amputation in patients with diabetes: cohort study

Julia Hippisley-Cox  1 , Carol Coupland  2
Affiliations

Development and validation of risk prediction equations to estimate future risk of blindness and lower limb amputation in patients with diabetes: cohort study

Julia Hippisley-Cox et al. BMJ. .

Abstract

Study question: Is it possible to develop and externally validate risk prediction equations to estimate the 10 year risk of blindness and lower limb amputation in patients with diabetes aged 25-84 years?

Methods: This was a prospective cohort study using routinely collected data from general practices in England contributing to the QResearch and Clinical Practice Research Datalink (CPRD) databases during the study period 1998-2014. The equations were developed using 763 QResearch practices (n=454,575 patients with diabetes) and validated in 254 different QResearch practices (n=142,419) and 357 CPRD practices (n=206,050). Cox proportional hazards models were used to derive separate risk equations for blindness and amputation in men and women that could be evaluated at 10 years. Measures of calibration and discrimination were calculated in the two validation cohorts.

Study answer and limitations: Risk prediction equations to quantify absolute risk of blindness and amputation in men and women with diabetes have been developed and externally validated. In the QResearch derivation cohort, 4822 new cases of lower limb amputation and 8063 new cases of blindness occurred during follow-up. The risk equations were well calibrated in both validation cohorts. Discrimination was good in men in the external CPRD cohort for amputation (D statistic 1.69, Harrell's C statistic 0.77) and blindness (D statistic 1.40, Harrell's C statistic 0.73), with similar results in women and in the QResearch validation cohort. The algorithms are based on variables that patients are likely to know or that are routinely recorded in general practice computer systems. They can be used to identify patients at high risk for prevention or further assessment. Limitations include lack of formally adjudicated outcomes, information bias, and missing data.

What this study adds: Patients with type 1 or type 2 diabetes are at increased risk of blindness and amputation but generally do not have accurate assessments of the magnitude of their individual risks. The new algorithms calculate the absolute risk of developing these complications over a 10 year period in patients with diabetes, taking account of their individual risk factors.

Funding, competing interests, data sharing: JH-C is co-director of QResearch, a not for profit organisation which is a joint partnership between the University of Nottingham and Egton Medical Information Systems, and is also a paid director of ClinRisk Ltd. CC is a paid consultant statistician for ClinRisk Ltd.

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Conflict of interest statement

Competing interests: Both authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: JH-C is co-director of QResearch, a not for profit organisation which is a joint partnership between the University of Nottingham and Egton Medical Information Systems (leading commercial supplier of IT for 60% of general practices in the UK), and is also a paid director of ClinRisk Ltd, which produces open and closed source software to ensure the reliable and updatable implementation of clinical risk equations within clinical computer systems to help improve patient care; CC is a paid consultant statistician for ClinRisk Ltd. This work and any views expressed within it are solely those of the co-authors and not of any affiliated bodies or organisations.

Figures

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Fig 1 Adjusted hazard ratios for blindness and lower limb amputation by age in derivation cohort
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Fig 2 Adjusted hazard ratios for blindness and lower limb amputation by HbA1c in derivation cohort
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Fig 3 Adjusted hazard ratios for blindness and lower limb amputation by systolic blood pressure in derivation cohort
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Fig 4 Mean predicted risks and observed risks of blindness and lower limb amputation at 10 years by 10th of predicted risk, applying equations to all men and women in QResearch validation cohort
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Fig 5 Mean predicted risks and observed risks of blindness and lower limb amputation at 10 years by 10th of predicted risk, applying equations to all men and women in CPRD validation cohort
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Fig 6 Web calculator applied to example female patient
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Fig 7 Web calculator applied to example male patient
See this image and copyright information in PMC

Comment in

References

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