Formidable impediments stand in the way of treatment development for lupus. These include the unwieldy size of current trials, international competition for scarce patients, complex outcome measures and a poor understanding of these outcomes in the world at large. The heterogeneity of the disease itself coupled to superimposition of variegated background polypharmacy has created enough immunological noise to virtually ensure the failure of lupus treatment trials, leaving an understandable suspicion that at least some of the results in testing failed drugs over the years may not have been negative, but merely uninterpretable. The authors have consulted with many clinical trial investigators, biopharmaceutical developers and stakeholders from government and voluntary sectors. This paper examines the available evidence that supports workable trial designs and proposes approaches to improve the odds of completing interpretable treatment development programs for lupus.
- clinical trials
- trial design
- outcome measures
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Contributors All authors contributed to the discussions and data interpretation that were used to form the recommendations contained in this paper and provided input to the manuscript and approved its final version. All consultants listed from the biotechnology sector reviewed the paper and provided helpful comments.
Funding JTM received grant/research support from Bristol-Myers Squibb Company, GSK group of companies, Xencor and Office of Minority Health. VPW received grant support from Celgene, Janssen, Biogen and Gilead. SM received grant support from BMS, AstraZeneca, HGS/GSK and Amgen.
Disclaimer The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Competing interests JTM, MD Consultant: Anthera, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb Company, Celgene Corporation, Eisai, EMD Serono; Exagen Diagnostics, Genentech, GSK, Gilead, ImmuPharma PLC, Horizon, Incyte, Janssen Pharmaceuticals; Mallinckrodt Pharmaceuticals, MedImmune/AstraZeneca, Neovacs SA, Pfizer, ReAlta, RRD International, Sanofi, Takeda Pharmaceuticals USA; UCB. VPW, MD Consultant: Resolve, Eli Lilly, Biogen, Idera, Medimmune, Genentech, BMS, Amgen, Penn own the copywright for the CLASI. IB MD, FRCP Research Support: Roche, GSK and Genzyme, and Sanofi Consulting/Speaker: Eli Lilly, AstraZeneca, GSK and UCB. IB is a National Institute for Health Research (NIHR) Senior Investigator and is funded by Arthritis Research UK, the Medical Research Council and the NIHR Manchester Biomedical Research Centre. BR MD Consultant: Alexion, Aurinia, Biogen, Biomarin, Bristol-Myers Squibb, EMB Serono, Fraizer, Genentech, Gilead, Eli Lilly, Lupus Foundation of America, Mallinckrodt, Pfizer, Pharmalink, Retrophin, Rigel, Trinity, Trinity Partners. JM MD, MMSc Consultant/Advisor: GSK and Biogen IDEC in Lupus indications. EG MD, MPH Consultant: Ablynx/PPDI Data Monitoring Board: Janssen Clinical Trial Investigator: Aurina, BMS, Genentech, GSK. CA MD Consultant: GSK Research Support: GlaxoSmithKline, EMD Serrono, Xencor, Takeda Pharmaceuticals and Janssen. BC MD Investigator: Daavin Corporation and Biogen. MD’E MD Consultant: Kezar Abbvie Independent Data Monitoring Committee: Janssen Genentech Biogen. KK MD Consultant: Amgen, Eli Lilly, Genentech, Roche, BMS, Medimmune, AstraZeneca, Janssen, Xencor, Anthera, Exagen, Baxalta, Biogen Idec, Sorrento Therapeutics Grants/Contracts: NIH, Lupus Research Alliance, Sanford Regenerative Medicine Consortium, Pfizer, Ablynx, Resolve, Celgene, Takeda, Questcor, Proximagen, UCB, Gilead, Ampel, Kirin. KC MD MPH Consultant: AstraZeneca GSK Merck Research Collaborations: AstraZeneca GSK Merck. Research Support: NIH. SM MD, MPH Consultant: Exagen Diagnotics, Inc; GSK, UCB Advisory Board, Lupus Foundation of America (Medical Director), AstraZeneca (Advisory Board).
Patient consent None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data presented in this article are already published and are not in possession of the authors.
Presented at The authors thank the following Panel of Expert Reviewers for their helpful comments and suggestions: Gabor Illei, MD MedImmune Jeffrey N. Siegel, MD Genentech, Inc. William J. Eastman, MD GlaxoSmithKline Bonnie Pobiner, PhD GlaxoSmithKline David Martin, MD Pfizer Inc. James B. Chung, MD, PhD Amgen Inc. Dorothy (Dottie) McCabe, PhD, FCP Boehringer Ingelheim Pharmaceuticals, Inc. John Throup, PhD Bristol-Myers Squibb Sabine Bongardt UCB BIOSCIENCES GmbH Amy H. Kao, MD, MPH, MS EMD Serono Research & Development Institute, Inc. (A business of Merck KGaA, Darmstadt, Germany)
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