De zoektocht naar effectieve behandelingen

In 2006 hield ik een inaugurele rede aan Nyenrode Business Universiteit te Breukelen. De rede werd uitgesproken bij het aanvaarden van het ambt van hoogleraar in de Kwantitatieve Bedrijfskundige Onderzoeksmethoden en had als titel “Meten en weten”. De volgende vraag stond centraal: Stel we hebben meetgegevens over bepaalde verschijnselen. Op welke wijze kunnen dan met behulp van moderne statistische methoden en technieken mogelijke oorzaak-gevolg relaties tussen twee of meer van deze verschijnselen worden vastgesteld? Ofwel: hoe kunnen op grond van verzamelde gegevens eventuele causale verbanden statistisch worden aangetoond? Deze vraag werd door mij aan de hand van bedrijfseconomische gegevens beantwoord. Vandaag richt ik mij op de medische sector. Ruim een jaar geleden werd ik benoemd als hoofd statistiek bij de unit Trials&Statistiek van het Erasmus Medisch Centrum (Erasmus MC) te Rotterdam. Enige tijd later volgde bij dit centrum tevens een benoeming als bijzonder hoogleraar, met als leerstoel ‘Biostatistiek in het Klinische Kankeronderzoek’. Een belangrijke doelstelling van deze leerstoel is een bijdrage te leveren aan de kwaliteit van het klinische kankeronderzoek en daarmee aan de effectiviteit van oncologische behandelingen. De titel van deze oratie luidt dan ook: “De zoektocht naar effectieve behandelingen”. De centrale vraag is: Op welke wijze kunnen moderne statistische methoden en technieken een bijdrage leveren aan het onderzoek naar effectieve behandelingen voor kankerpatiënten? Het gaat – net als in 2006 – nog steeds over statistiek, maar het toepassingsgebied is totaal anders

Modeling ICT Perceptions and Views of Urban Front Liners

This paper offers both a conceptual and an operationalmodel that aims to map out the causes and implicationsof ICT perceptions and views of urban policy makersand/or administrative officials (denoted as urban frontliners). This is followed by the presentation of an opera-tional path model, viz. a linear structural equations model(Lisrel). The model serves to describe and test the rela-tionships between perceptions of the city, policy makers'beliefs about ICT and the associated urban ICT policy.According to the model, respondents that perceive theircity as having many urban functions (e.g., commercialcentre, service centre, higher education centre) have moreawareness to various ICT tools and are likely to consider amultiplicity of ICT measures as relevant to their city. Re-spondents that consider their city as having severe bottle-necks (e.g., traffic congestion, housing shortage) are lesslikely to think of ICT measures and ICT -related goals asrelevant to their city, nor that the municipality impactssignificantly on ICT in the city. Furthermore, respondentsthat perceive their city as suffering from many socio-economic problems (unemployment, ageing population,industrial decline and so on), are likely to consider manyICT tools as relevant to their city, although they have a lowawareness of the specific tools to be deployed. Finally,respondents who believe that ICT will affect significantly(and positively) the city and its administration, tend to at-tach a high municipal influence on ICT, and consider manyICT initiatives as relevant to their city

Developments in statistical evaluation of clinical trials

This book describes various ways of approaching and interpreting the data produced by clinical trial studies, with a special emphasis on the essential role that biostatistics plays in clinical trials. Over the past few decades the role of statistics in the evaluation and interpretation of clinical data has become of paramount importance. As a result the standards of clinical study design, conduct and interpretation have undergone substantial improvement. The book includes 18 carefully reviewed chapters on recent developments in clinical trials and their statistical evaluation, with each chapter providing one or more examples involving typical data sets, enabling readers to apply the proposed procedures. The chapters employ a uniform style to enhance comparability between the approaches

Increased aortic stiffness and blood pressure in non-classic Pompe disease

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99)

Is the Clinical Risk Score for Patients with Colorectal Liver Metastases Still Useable in the Era of Effective Neoadjuvant Chemotherapy?

Background: Several clinical risk scores (CRSs) for the outcome of patients with colorectal liver metastases have been validated, but not in patients undergoing neoadjuvant chemotherapy. Therefore, this study evaluates the predictive value of these CRSs in this specific group. Methods: Between January 2000 and December 2008, all patients undergoing a metastasectomy were analyzed and divided into two groups: 193 patients did not receive neoadjuvant chemotherapy (group A), and 159 patients received neoadjuvant chemotherapy (group B). In group B, the CRSs were calculated before and after administration of neoadjuvant chemotherapy. Results were evaluated by using the CRSs proposed by Nordlinger et al., Fong et al., Nagashima et al., and Konopke et al. Results: In groups A and B, the overall median survival was 43 and 47 months, respectively (P = 0.648). In group A, all CRSs used were of statistically significant predictive value. Before administration of neoadjuvant chemotherapy, only the Nordlinger score was of predictive value. After administration of neoadjuvant chemotherapy, all CRSs were of predictive value again, except for the Konopke score. Conclusions: Traditional CRSs are not a reliable prognostic tool when used in patients before treatment with neoadjuvant chemotherapy. However, CRSs assessed after the administration of neoadjuvant chemotherapy are useful to predict prognosis

Increased aortic stiffness and blood pressure in non-classic Pompe disease

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20 %), more Pompe patients had a history of hypertension (36 %, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly

Outcome of Microscopic Incomplete Resection (R1) of Colorectal Liver Metastases in the Era of Neoadjuvant Chemotherapy

Background: Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM. Methods: Between January 2000 and December 2008, all consecutive patients undergoing liver resection for CRLM were analyzed. Patients were divided into those who did and did not receive neoadjuvant chemotherapy. The outcome after R0 (tumor-free margin >0 mm) and R1 (tumor-free margin 0 mm) resection was compared. Results: A total of 264 were eligible for analysis. Median follow-up was 34 months. Patients without chemotherapy showed a significant difference in median disease-free survival (DFS) after R0 or R1 resection: 17 [95% confidence interval (CI) 10-24] months versus 8 (95% CI 4-12) months (P < 0.001), whereas in