Correction: Designing integrated early-phase protocols to reduce substantial modifications, including considerations for patient cohorts – a multi-stakeholder consensus view for a practical approach in Germany

Frontiers in Pharmacology, vol. 17, pp. 1948963

Abstract

Adding/removing text We have identified three instances where we incorrectly used quotation marks although the wording parphrased the guideline rather than quoting it verbatim. In addition, one incorrect section reference to the EMA FIH guideline has been identified. We note that in each instance the meaning remains unchanged. However, we wish to correct these instances to avoid attributing wording to the EMA FIH guideline.All corrections concern Section 2.2 "Decision criteria for progressing between trial parts" 1. A correction has been made to section 2.2, paragraph 1.In the published article, the text reads:According to EMA FIH (Section 8.2.1): "The protocol should define dose escalation and stopping rules and other criteria guiding the decision to progress from one part of the trial to another."In line with EMA FIH Sections 7.4, 8.2.2 and 8.2.9, the protocol should define dose escalation criteria, stopping rules and criteria guiding the decision to progress from one trial part to another.The original version of this article has been updated. 2. A correction has been made to section 2.2, paragraph 2.In the published article, the text reads: Section 6.7 of the guideline further requires that for patient populations, the starting dose is expected to have a minimal pharmacological effect and must be safe to use This has been corrected to read: Section 7.3 of the guideline further requires that for patient populations, the starting dose is expected to have a minimal pharmacological effect and must be safe to use.The original version of this article has been updated.A correction has been made to section 2.2, paragraph 3.In the published article, the text reads:The guideline emphasises that escalation steps should be conservative and justified, especially once a pharmacologically active range has been reached. It explicitly advises that "when pharmacodynamic activity has been reached, dose increments above a two-fold increase should be avoided unless appropriately justified" (EMA FIH, Section 8.2.2).The guideline emphasises that escalation steps should be conservative and justified, especially once a pharmacologically active range has been reached (EMA FIH, Sections 7.4, 7.5). Based on the consensus process reported in this article, when pharmacodynamic activity has been reached, dose increments above a two-fold increase should be avoided unless appropriately justified.The original version of this article has been updated.In the published article, the text reads:Optional parts and flexible design elements (e.g., optional cohorts) must also follow predefined boundaries. As stated in Section 8.2.2: "All parts and options within an integrated protocol should be predefined, and the data to be used to make decisions about proceeding should be clearly described."This has been corrected to read: Optional parts and flexible design elements (e.g., optional cohorts) must also follow predefined boundaries. In line with EMA FIH sections 8.2.2 and 8.2.8, all parts and options within an integrated protocol should be predefined, and the data to be used to make decisions about proceeding should be clearly described.End of template. If you would like to request a correction for a reason not seen here, please contact the journal's editorial office.

Authors 19

1. R. Schultz-Heienbrok

   Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Charité Research Organisation GmbH

2. S. Baumann

   Clinical Research Services

   Affiliation as printed

   CRS Clinical Research Services Management

3. R. Böhm

   SocraTec R&D (Germany) · University Hospital Schleswig-Holstein

   Affiliation as printed

   SocraTec R&D

   Universitätsklinikum Schleswig-Holstein

4. A. Bonertz

   Paul Ehrlich Institut

   Affiliation as printed

   Paul-Ehrlich-Institut

5. K. Breithaupt-Groegler
   Affiliation as printed

   Consultant Clinical Pharmacology

6. U. Buckpesch-Heberer

   Paul Ehrlich Institut

   Affiliation as printed

   Paul-Ehrlich-Institut

7. M. Coenen

   University Hospital Bonn

   Affiliation as printed

   Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn

8. K. Erb-Zohar
   Affiliation as printed

   Clinphase

9. N. Faisst

   Dr Falk Pharma (Germany)

   Affiliation as printed

   Dr. Falk Pharma GmbH

10. G. Grass
    Affiliation as printed

    Spezialisierte Ethikkommission für besondere Verfahren

11. J. Höchel

    Bayer (Germany)

    Affiliation as printed

    Bayer AG

12. A. Kovar

    Sanofi (France)

    Affiliation as printed

    Sanofi

13. A. Muehlenbroich

    Novartis (Switzerland)

    Affiliation as printed

    Novartis

14. J. Rengelshausen Aachen

    Universitätsklinikum Aachen

    Affiliation as printed

    Uniklinik RWTH Aachen

15. C. Riedel

    Federal Institute for Drugs and Medical Devices

    Affiliation as printed

    Bundesinstitut für Arzneimittel und Medizinprodukte

16. B. Schug

    SocraTec R&D (Germany)

    Affiliation as printed

    SocraTec R&D

17. T. Sudhop

    Federal Institute for Drugs and Medical Devices

    Affiliation as printed

    Bundesinstitut für Arzneimittel und Medizinprodukte

18. A. Warnke

    SocraTec R&D (Germany)

    Affiliation as printed

    SocraTec R&D

19. B. Ziegele

    University Hospital Bonn

    Affiliation as printed

    Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn