Enhancing quality and impact of early phase dose-finding clinical trial protocols: SPIRIT Dose-finding Extension (SPIRIT-DEFINE) guidance.

Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work. JdB has served on advisory boards and received fees from companies including Amgen, Astra Zeneca, Astellas, Bayer, Bioxcel Therapeutics, Daiichi, Genentech/Roche, GSK, Harpoon, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp and Dohme, Pfizer, and Sanofi Aventis; is an employee of the Institute of Cancer Research (ICR), which have received funding or other support for his research work from AZ, Astellas, Bayer, Cellcentric, Daiichi, Genentech, Genmab, GSK, Janssen, Merck Serono, Merck Sharp & Dohme (MSD), Menarini/Silicon Biosystems, Orion, Sanofi Aventis, Sierra Oncology, Taiho, Pfizer, and Vertex (the ICR has a commercial interest in abiraterone and poly (ADP-ribose) polymerase (PARP) inhibition in DNA repair defective cancers and PI3K/AKT pathway inhibitors (no personal income)); was named as an inventor, with no financial interest, for patent 8 822 438, submitted by Janssen that covers the use of abiraterone acetate with corticosteroids; has been the chief investigator/principal investigator of many industry sponsored clinical trials; and is a National Institute for Health Research (NIHR) senior investigator. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. AM is employed by GSK. TRJE has received honorariums for consultancies (payable to the employing institution) from Ascelia, Astra Zeneca, Bayer, Bicycle Therapeutics, Bristol Myers Squibb, Celgene Eisai, Karus Therapeutics, Medivir, MSD, Otsuka, Roche, and Seagen; honorariums for speaker’s fees (payable to employing institution) from Astra Zeneca, Ascelia, Bayer, Bicycle Therapeutics, Bristol Myers Squibb, Celgene, Eisai, Nucana, Otsuka, Medivir, MSD, Roche, Seagen, and United Medical; support of costs of commercial clinical trials (payable to employing institution) from Astra Zeneca, Basilea, Bayer, Celgene, MiNa Therapeutics, Roche, Pfizer, Sierra, Lilly, Eisai, Glaxo Smith Kline, Novartis, Bicycle Therapeutics, Johnson and Johnson, CytomX, Vertex, Plexxikon, Boehringer, Athinex, Adaptimmune, Bristol Myers Squibb, MSD, Medivir, Versatem, Nucana, Immnuocore, Berg, Beigene, Iovance, Modulate, BiolinerX, Merck Serono, Nurix Therapeutics, T3P, Janssen Clovis, Sanofi-Aventis, Halozyme, Starpharma, Union Chimique Belge, Sapience, Seagen, Avacta, and Codiak; and funding from Cancer Research UK, Chief Scientist’s Office Scotland, and Medical Research Council UK; is the editor-in-chief of the British Journal of Cancer and has an honorary clinical contract with the NHS Greater Glasgow and Clyde Health Board. RP is an employee and a stockholder in F Hoffmann la Roche, and a family member is also an employee and a stockholder of F Hoffmann la Roche. KSH declares grant funding (payable to the employing institution) received by the Medical Research Future Fund (grant 2007425), National Health and Medical Research Council of Australia (grants 2016420 and 2015705), and Heart Foundation of Australia (grant 106607). SH and A-WC are members of the SPIRIT-CONSORT executive group and are leading the current update of the SPIRIT 2013 and CONSORT 2010 reporting guidelines, funded by the UK Medical Research Council NIHR Better Methods, Better Research (MR/W020483/1). MU acted as consultant for eXYSTAT, Saryga, PTC Therapeutics International, and ImCheck Therapeutics. MC is director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, director of the Centre for Patient Reported Outcomes Research, and is a NIHR senior investigator. MJC has received funding from the NIHR, UK Research and Innovation (UKRI), NIHR Birmingham Biomedical Research Centre, NIHR Surgical Reconstruction and Microbiology Research Centre, NIHR, Applied Research Collaboration West Midlands, UK SPINE, Research England, European Regional Development Fund DEMAND Hub at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, and NIHR Birmingham-Oxford Blood and Transplant Research Unit in Precision Transplant and Cellular Therapeutics; funding from Health Data Research UK, Innovate UK (part of UKRI), Macmillan Cancer Support, UCB Pharma, Janssen, GSK, Gilead Sciences, European Commission, European Federation of Pharmaceutical Industries and Associations, and the Brain Tumour Charity; and personal fees from Aparito, CIS Oncology, Takeda Pharmaceuticals, Merck, Daiichi Sankyo, Glaukos, GSK, the Patient-Centered Outcomes Research Institute, Genentech, and Vertex Pharmaceuticals outside the submitted work; has received lecture fees from the University of Maastricht, Maastricht, Netherlands; a family member owns shares in GSK. DPR is the volunteer vice president of the Canadian Arthritis Patient Alliance, a patient led and run organisation that derives most funding from independent grants from pharmaceutical companies. OB is an employee of Bayer AG. JM is an employee of Cytel (Australia). LS declares grant funding from AstraZeneca, Bayer, Pfizer, Merck, Roche, REPARE, Treadwell, and Janssen; has provided expert testimony for CADTH Health Canada; and declares AstraZeneca stock/options ownership. LM received honorariums for speaker fees from Bayer and as co-organiser, chair, and speaker at two educational preceptorships (online webinars); and advisory board/consultancy honorariums from Tesaro, BMS, and Illumina; is also a member of external data monitoring committees for early phase clinical trials run between Eisai and Merck. RL is an employee and stockholder of Bristol Myers Squibb. JB declares consultancy fees from Mirati, Insmed, Oxford BioTherapeutics, Biosapien, EMD Serono, Ipsen, Merck Sharp and Dohme, Perus, BMS, and Bexion; declares grant funding from Abbvie, Astellas, Atreca, Bayer, Dragonfly, I-Mab, Lilly, Incyte, EMD Serono, Pfizer, BMS, Transcenta Therapeutics, Tyra, Totus, Sumitomo Dainippon Pharma Oncology, 23 and me, Parthenon, and Hibercell; and sits on data safety monitoring committees for Astra Zeneca, Novocure, and Boehringer-Ingelheim. All other authors declare no conflict of interest.