Enhancing quality and impact of early phase dose-finding cli

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

SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 provides guidance for clinical trial protocol writing. However, neither the original guidance nor its extensions adequately cover the features of early phase dose-finding trials. The SPIRIT Dose-finding Extension (DEFINE) statement is a new guideline that provides recommendations for essential items that should be provided in the protocols of these trials. It details extensions to the SPIRIT 2013 guidance, incorporating 17 new items and modifying 15 existing items. The purpose of this guideline is to promote transparency, completeness, reproducibility of methods, and interpretation of early phase dose-finding trial protocols. It is envisioned that the resulting improvements in the design and conduct of early phase clinical trials will ultimately reduce research inefficiencies and inconsistencies, driving transformational advances in clinical care.

Developing an intervention is a lengthy process pursued in stages where decisions are based on balance of benefits and risks or harms of the intervention under investigation. Lack of efficacy or evidence of harm due to adverse safety profiles are common reasons for phase 2 and phase 3 trials to be unsuccessful.12 Phase 3 trial failures can reflect incorrect decisions made at earlier stages, including in early phase dose-finding (EPDF) trials (commonly known as phase 1, phase 1/2, or first-in-human trials). Reasons why interventions do not progress or succeed in later stages of clinical development include misleading preclinical studies, inadequate participant selection, inefficient trial design, suboptimal biomarker or outcome choices, and poor dose selection. The same reasons can also contribute to early discontinuation of promising interventions.

EPDF trials typically evaluate new interventions that can be used in different doses and can be pharmacological (chemical or biological—eg, drugs, vaccines, cell therapies, gene therapies), non-pharmacological (eg, radiotherapy, devices, rehabilitation, digital therapies), or a combination of both. They usually include a small number of …

Related Keywords

Canada , Glasgow , Glasgow City , United Kingdom , Australia , Maastricht , Limburg , Netherlands , West Midlands , United Kingdom General , United States , Canadian , America , British , Scotland , Daiichi Sankyo , Oxford Biotherapeutics , Janssen Clovis , Lilly Incyte , Smith Kline , Celgene Eisai , Sumitomo Dainippon Pharma , Genentech Roche , Astra Zeneca , Merck Serono , Canadian Arthritis Patient Alliance , Outcomes Research Institute , Vertex Pharmaceuticals , Gilead Sciences , European Commission , Birmingham Health Partners Centre For Regulatory Science , Serono , Research Future Fund , United Kingdom Health Research Authority , Health Canada , Microbiology Research Centre , Bayer Ag , Research England , Regulatory Agency , Research Council Of Australia , Heart Foundation Of Australia , Union Chimique Belge , National Institute For Health , Royal Marsden Cancer Charity , Bristol Myers Squibb , European Regional Development Fund , Research Collaboration West Midlands , Genentech , University Hospitals Birmingham , Centre For Patient Reported Outcomes Research , Therapeutics International , Scientist Office Scotland , Novartis , Oak Foundation , Better Research , Research Council , Astrazeneca , Amgen , Research Unit In Precision , Birmingham Biomedical Research Centre , Clyde Health Board , Health Data Research United Kingdom , National Health , Pfizer , Sanofi Aventis , Institute Of Cancer Research , Cancer Research United Kingdom , International Delphi , European Federation Of Pharmaceutical Industries , Experimental Cancer Medicine Centre , United Kingdom Research , United Kingdom Medical Research Council , Research Council United Kingdom , University Of Maastricht , University Of Birmingham , Takeda Pharmaceuticals , Department Of Health , Brain Tumour Charity , Care Research , National Institute For Health Research , Imperial Biomedical Research Centre , Standard Protocol Items , Interventional Trials , Cancer Research , Clinical Research , International Council , Technical Requirements , Human Use , North America , National Institute , Imperial Biomedical Research , Medical Research Council , Heart Foundation , Cancer Biomedical Research , Royal Marsden , Medical Research , Consensus Meeting , Bioxcel Therapeutics , Imcheck Therapeutics , Merck Sharp , Silicon Biosystems , Sierra Oncology , Health Research , Bicycle Therapeutics , Karus Therapeutics , United Medical , Mina Therapeutics , Glaxo Smith Kline , Nurix Therapeutics , Chief Scientist , Office Scotland , Medical Research Council United Kingdom , British Journal , Clyde Health , Medical Research Future Fund , Birmingham Health Partners Centre , Regulatory Science , Patient Reported Outcomes Research , Biomedical Research Centre , Applied Research Collaboration West Midlands , Oxford Blood , Transplant Research Unit , Precision Transplant , Cellular Therapeutics , Innovate United Kingdom , Macmillan Cancer Support , European Federation , Pharmaceutical Industries , Patient Centered Outcomes Research Institute , Bristol Myers , Transcenta Therapeutics , Sumitomo Dainippon Pharma Oncology ,

© 2025 Vimarsana