% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Labrenz:182282,
      author       = {J. Labrenz$^*$ and D. Edelmann$^*$ and J. Heitmann$^*$ and
                      H. Salih$^*$ and A. Kopp-Schneider$^*$ and R. Schlenk$^*$},
      title        = {{P}erformance of phase-{I} dose finding designs with and
                      without a run-in intra-patient dose escalation stage.},
      journal      = {Pharmaceutical statistics},
      volume       = {22},
      number       = {2},
      issn         = {1539-1604},
      address      = {New York, NY},
      publisher    = {Wiley},
      reportid     = {DKFZ-2022-02542},
      pages        = {236-247},
      year         = {2023},
      note         = {#LA:C060#LA:W010# / 2023 Mar;22(2):236-247},
      abstract     = {Dose-finding designs for phase-I trials aim to determine
                      the recommended phase-II dose (RP2D) for further phase-II
                      drug development. If the trial includes patients for whom
                      several lines of standard therapy failed or if the toxicity
                      of the investigated agent does not necessarily increase with
                      dose, optimal dose-finding designs should limit the
                      frequency of treatment with suboptimal doses. We propose a
                      two-stage design strategy with a run-in intra-patient dose
                      escalation part followed by a more traditional dose-finding
                      design. We conduct simulation studies to compare the 3 + 3
                      design, the Bayesian Optimal Interval Design (BOIN) and the
                      Continual Reassessment Method (CRM) with and without
                      intra-patient dose escalation. The endpoints are accuracy,
                      sample size, safety, and therapeutic efficiency. For
                      scenarios where the correct RP2D is the highest dose,
                      inclusion of an intra-patient dose escalation stage
                      generally increases accuracy and therapeutic efficiency.
                      However, for scenarios where the correct RP2D is below the
                      highest dose, intra-patient dose escalation designs lead to
                      increased risk of overdosing and an overestimation of RP2D.
                      The magnitude of the change in operating characteristics
                      after including an intra-patient stage is largest for the 3
                      + 3 design, decreases for the BOIN and is smallest for the
                      CRM.},
      keywords     = {dose escalation (Other) / dose-finding (Other) /
                      intra-patient (Other) / maximum tolerated dose (Other) /
                      phase-I (Other)},
      cin          = {C060 / TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331 / I:(DE-He78)TU01-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36285348},
      doi          = {10.1002/pst.2268},
      url          = {https://inrepo02.dkfz.de/record/182282},
}