The main objective of this thesis is to provide a conceptual framework for the use of Central Nervous System (CNS) biomarkers in early phase clinical drug development. In the Introduction the... Show moreThe main objective of this thesis is to provide a conceptual framework for the use of Central Nervous System (CNS) biomarkers in early phase clinical drug development. In the Introduction the current use of biomarkers in early CNS drug development is discussed. A conceptual framework for the classification of biomarkers is suggested, based on general questions that these markers should provide information on. The body of this thesis (Chapters 1-7) exemplifies the use of these markers within this conceptual framework. In the Conclusions and Discussion a critical evaluation of the presented conceptual biomarker framework is give and directions for future biomarker research are offered. Show less
In the group of women with equivocal cytology (Pap II) 15-30% have high-grade CIN or even cervical carcinoma. This high percentage underlines the importance of identifying these women. The... Show moreIn the group of women with equivocal cytology (Pap II) 15-30% have high-grade CIN or even cervical carcinoma. This high percentage underlines the importance of identifying these women. The sensitivity and specificity of cervical cytology are low. There are other methods besides cytology to identify women at risk for high-grade CIN or cervical cancer. This thesis focuses mainly on the prevalence of high-grade CIN in women with equivocal cytology (chapter 2) and on other methods than cytology alone to identify women at risk for high-grade CIN in this category of abnormal cytology. Methods like colposcopy (chapter 2, 3), detection of high-risk HPV (chapter 2, 5), persistence/ clearance of HPV (chapter 4), HPV viral load (chapter 4 and 5), and biomarker Ki-67 (chapter 6) were studied to this means. Show less
