TY  - JOUR
A1  - Gökbuget, N.
A1  - Kelsh, M.
A1  - Chia, V.
A1  - Advani, A.
A1  - Bassan, R.
A1  - Dombret, H.
A1  - Doubek, M.
A1  - Fielding, A. K.
A1  - Giebel, S.
A1  - Haddad, V.
A1  - Hoelzer, D.
A1  - Holland, C.
A1  - Ifrah, N.
A1  - Katz, A.
A1  - Maniar, T.
A1  - Martinelli, G.
A1  - Morgades, M.
A1  - O'Brien, S.
A1  - Ribera, J.-M.
A1  - Rowe, J. M.
A1  - Stein, A.
A1  - Topp, M.
A1  - Wadleigh, M.
A1  - Kantarjian, H.
T1  - Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia
JF  - Blood Cancer Journal
N2  - We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20–27%) and a median OS of 3.3 months (95% CI: 2.8–3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36–50%) and a median OS of 6.1 months (95% CI: 4.2–7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67–4.31) and improved OS (HR=0.536, 95% CI: 0.394–0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.
KW  - Acute lymphocytic leukaemia
KW  - Drug development
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164495
VL  - 6
ER  - 
TY  - JOUR
A1  - Gerlach, Manfred
A1  - Maetzler, Walter
A1  - Broich, Karl
A1  - Hampel, Harald
A1  - Rems, Lucas
A1  - Reum, Torsten
A1  - Riederer, Peter
A1  - Stöffler, Albrecht
A1  - Streffer, Johannes
A1  - Berg, Daniela
T1  - Biomarker candidates of neurodegeneration in Parkinson’s disease for the evaluation of disease-modifying therapeutics
JF  - Journal of Neural Transmission
N2  - Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson’s disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.
KW  - Parkinson’s disease
KW  - Disease-modifying therapies
KW  - Neuroprotection
KW  - Biomarkers
KW  - Surrogate endpoints
KW  - Drug development
KW  - Disease progression
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133856
VL  - 119
IS  - 1
ER  -