BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD); however, the natural course of disease progression is heterogeneous between patients. This study aimed to develop a natural history model of ADPKD that predicted progression rates and long-term outcomes in patients with differing baseline characteristics.MethodsThe ADPKD Outcomes Model (ADPKD-OM) was developed using available patient-level data from the placebo arm of the Tolvaptan Efficacy and Safety in Management of ADPKD and its Outcomes Study (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948). Multivariable regression equations estimating annual rates of ADPKD progression, in terms of total kidney volume (TKV) and estimated glomerular filtration rate, formed the basis of the lifetime patient-level simulation model. Outputs of the ADPKD-OM were compared against external data sources to validate model accuracy and generalisability to other ADPKD patient populations, then used to predict long-term outcomes in a cohort matched to the overall TEMPO 3:4 study population.ResultsA cohort with baseline patient characteristics consistent with TEMPO 3:4 was predicted to reach ESRD at a mean age of 52 years. Most patients (85%) were predicted to reach ESRD by the age of 65 years, with many progressing to ESRD earlier in life (18, 36 and 56% by the age of 45, 50 and 55 years, respectively). Consistent with previous research and clinical opinion, analyses supported the selection of baseline TKV as a prognostic factor for ADPKD progression, and demonstrated its value as a strong predictor of future ESRD risk. Validation exercises and illustrative analyses confirmed the ability of the ADPKD-OM to accurately predict disease progression towards ESRD across a range of clinically-relevant patient profiles.ConclusionsThe ADPKD-OM represents a robust tool to predict natural disease progression and long-term outcomes in ADPKD patients, based on readily available and/or measurable clinical characteristics. In conjunction with clinical judgement, it has the potential to support decision-making in research and clinical practice.Electronic supplementary materialThe online version of this article (10.1186/s12882-017-0804-2) contains supplementary material, which is available to authorized users.

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dence interval 67-83%) of instances compared with the control method (25%, 95%CI 17-33%), and among 83% (95%CI 76-91%) of positively-GDP-associated cancers compared with 17% (95%CI 9-24%) for the control method. There was no significant difference between the two methods for negatively-GDP-associated cancers. In terms of the relative magnitude of change compared to the actual incidences, there was no significant difference between the GDP-based forecast incidences and the control (mean magnitude difference 3.8%, 95% CI -3.5% -11.0%). ConClusions: During epidemiological transition, cancer incidence is unlikely to remain static and so developing a proxy variable to evaluate risk over time is important. Using GDP as a proxy variable is preferable to the alternative of projecting historical values forward unchanged in terms of directional effect. However our study found no significant difference in terms of relative magnitude of the change over time. This latter result may be due to a small sample size of registries, indicating a need for further research.

controls based on gender, birth year and year of start enrolment in the PHARMO Database Network. Matched controls received the same index date as their matched case. Cases and controls were not allowed to have a diagnosis of cancer before index date. The association between the use of antipsychotics (either typical, atypical or lithium) before index date and risk of CRC was estimated using conditional logistic regression. Results: A total of 29,490 CRC cases and 117,960 controls were identified. The use of any antipsychotic before index date was slightly higher among controls compared to CRC cases [3% vs. 2%] resulted in an odds ratio (OR) of 0.64 (95% CI 0.59-0.70) for CRC. Stratification by typical or atypical antipsychotics yielded almost the same OR. A different OR was seen for lithium: 1.17 (95% CI: 0.94-1.45) and increased with long term use [≥ 5 years: 1.60 (95% CI: 1.12-2.31). Also, the OR of lithium differed between tumour sites: [proximal colon: 1.09 (95% CI: 0.78-1.53); distal colon: 1.44 (95% CI: 1.00-2.08) and rectum: 1.04 (95% CI: 0.65-1.65)], which was not seen for atypical or typical antipsychotics. ConClusions: Overall, no association was seen between the use of antipsychotics and the risk of CRC. However, an increased risk of CRC was seen with long term lithium use and differed between specific tumour sites.