Background: Köhne et al. [Ann Oncol 2002;13:308–317] showed that four prognostic variables can be used to classify patients with metastatic colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)/leucovorin (LV) into three risk groups with different overall survival (OS). This model was applied to data from phase II/III trials of first-line bevacizumab plus 5-FU/LV with/without irinotecan (IFL). Methods: Data on tumor sites, Eastern Cooperative Oncology Group performance status, alkaline phosphatase levels and white blood cell counts were used to classify patients into Köhne prognostic high-, intermediate- and low-risk groups. Median OS and progression-free survival (PFS) were calculated for patients receiving 5-FU/LV plus bevacizumab or placebo (n = 489) and IFL plus bevacizumab or placebo (n = 812). Results: Median OS was longer in 5-FU/LV/bevacizumab (11.2–22.6 months) than in the 5-FU/LV/placebo (5.7–17.5 months), and in the IFL/bevacizumab arm (14.3–22.5 months) than in the IFL/placebo arm (8.4–17.9 months) across the Köhne high-, intermediate- and low-risk groups. The addition of bevacizumab also extended median PFS across the Köhne risk groups compared with placebo. Conclusions: Bevacizumab improves OS and PFS across the Köhne risk classification in patients with metastatic CRC. The Köhne model can be extended to patients treated with 5-FU/LV/bevacizumab, IFL and IFL/bevacizumab and to PFS data.

As has been shown by the authors of a paper recently published in this journal, a deviation from a long-term trend in perinatal mortality within the former Federal Republic of Germany occurred in 1987, i.e. 1 year following the Chernobyl disaster. It is the aim of this study to make a comparison between the areas of the state Bavaria. Germany, with different fallout levels as well as between the observed and expected numbers of perinatal deaths relating to these areas. The expected numbers of perinatal deaths, defined as external standard, were derived from the remainder of the former FRG. Testing an a priori formulated hypothesis revealed no differences in the temporal development of perinatal mortality between the areas with different fallout levels and subsequent exposure. Including May 1986 into the analysis revealed a significant increase during the first 3 months after the accident, which is due to an excess in May alone. Since no elevated radiation risks for the last days in utero are known, the additional Chernobyl radiation exposure is not plausible as a causative agent. Further analyses on stillbirths showed an increase in Southern Bavaria during the first 2 years following the accident. Later on, the rates were comparable to the expected values again.

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ObjectivesEvidence requirements and assessment methods access differ between health technology assessment (HTA) agencies. The HTA Core Model® provides a standardized approach to HTA, targeting evidence sharing and collaboration between participating HTA bodies. It is fit for purpose from an industry perspective and was used by pharmaceutical company Roche to develop a framework for internal assessment of evidence required for market access and coverage/reimbursement (“access evidence”).MethodsTools were developed to systematically scope, assess, plan, and summarize access evidence generation. The tools were based mainly on the first four HTA Core Model® domains and rolled-out in selected development teams in 2017. Five months after full implementation, the impact of tools was assessed in an internal survey.ResultsSystematic access evidence generation started with the Access Evidence Questionnaire, to scope evidence requirements and identify evidence gaps. Findings were summarized in the Access Evidence Metric, which assessed the alignment of available/planned evidence against HTA bodies’ requirements and developed scope mitigation strategies. The Access Evidence Plan was then used to plan and document (additional) evidence generation. Once generated, evidence was summarized in the Access Evidence Dossier. A survey of twenty-seven Roche employees involved in evidence generation showed that the tools made discussions around access strategies and evidence more efficient and transparent.ConclusionsThe HTA Core Model® provided a useful framework around which to optimize internal evidence generation and assessment. The benefits of using a standardized HTA approach in industry mirror those expected from implementing the HTA Core Model® in HTA agencies.

The study presents data on cardiovascular malformations in Bavarian livebirths, born between 1984 and 1991. Cases have been ascertained retrospectively by reviewing hospital records of all children being referred to a children's hospital up to 2 years of age. The classification scheme was based on abnormalities in developmental mechanisms. Among 984,570 livebirths, 7020 cases with structural congenital heart disease were identified. The birth prevalence was 7.1 per 1000 livebirths. Between 1984 and 1991, total prevalence increased from 5.9/10(3) to 8.0/10(3). Prevalence in males was 7.3/10(3) and in females 6.9/10(3). 78.1% of all heart defects were isolated, the remaining 21.9% were associated either with chromosomal abnormalities (9.6%), non-chromosomal syndromes (1.0%), or noncardiac malformations of other organ systems (11.3%). Total fatality rate was 12.0%, with two thirds of deaths occurring within a month of birth or the following month of life. Data were compared with those of the Baltimore-Washington Infant Study. This study presents for the first time regional data on birth prevalences of congenital heart defects in Germany. The classification scheme reduces the wide spectrum of phenotype cardiovascular defects to several pathogenetic groups. The defects in each group may be related to similar causal factors.