RESEARCH
Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors
(JAMA Network Open, 2023)
By Valerie Jentzsch, Leeza Osipenko, Jack Scannell, John Hickman
In this paper we are aiming to answer the following question: what are the associated expenses of clinical research and what factors underly the translational failure of inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) in oncology? Our findings show that 16 inhibitors of IGF-1R underwent 183 clinical trials in more than 12 000 patients; none of the agents was approved for clinical use in oncology practice and the trials were estimated to have had expenses of greater than $1.6 billion. Half of the published in vivo preclinical data analyzed showed less than a 50% inhibition of tumor growth by IGF-1R inhibitors. With high attrition rates for oncology drugs, the fruitless and expensive clinical trials of 16 IGF-1R inhibitors draw attention to the need for improved preclinical models and better decision-making before trials are launched, reducing substantial financial losses and avoiding exposure of patients to potential toxic effects.
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Invited Commentary
Journeys to Failure that Litter the Path to Developing New Cancer Therapeutics
Tito Fojo, MD, PhD
Endpoints News: Failed trials for 16 IGF-1R inhibitors and $1.6B later: Time for better preclinical models? by Zachary Brennan
Cancer Therapy Advisor: Failed Oncology Trials May Cost Up to $60 Billion Per Year by Hibah Khaja
Are European clinical trial funders policies on clinical trial registration and reporting improving? A cross-sectional study
(J Clin Transl Sci. 2023)
by Marguerite O’Riordan, Martin Haslberger, Carolina Cruz, Tarik Suljic, Martin Ringsten, Till Bruckner
In this study we assess the extent to which the clinical trial registration and reporting policies of 25 of the world’s largest public and philanthropic medical research funders meet best practice benchmarks as stipulated by the 2017 WHO Joint Statement, and document changes in the policies and monitoring systems of 19 European funders over the past year.
This study enables funders worldwide to identify and address gaps in their clinical trial transparency policies by pinpointing exactly where they currently fall short of WHO best practices. It also enables policymakers and citizens to assess whether public bodies tasked with furthering medical knowledge have adopted adequate safeguards against research waste and publication bias.
Data redaction practices in NICE technology appraisals from 1999 to 2019
(BMJ Open, 2021)
This paper presents a complete audit of data redaction practices in all active technology appraisals (TA) and highly specialised technology (HST) evaluations issued by the National Institute for Health and Care Excellence (NICE) from the conception of the Institute to September 2019. Over 81.6% of appraisals feature data redactions. Data redaction increased substantially over time, and is currently at its highest level with 100% of TAs having at least some data redaction in 2019/2020, 96% of appraisals in 2018/2019% and 94% of appraisals in 2017/2018. Policy changes are needed to stop clinical data redaction practice at NICE.
UK government refuses to discuss ‘alarming’ NICE data redactions
Pressure Builds On England’s HTA Body & Industry To Reduce Data Redaction
ICMJE statement on clinical trial data contained in assessment reports
Health groups call for end to redacted clinical trial data in technology assessments
BMJ News Jan 19, 2022
Feb 16, 2022
Why NICE’s Lack of Data Transparency Undermines Priority Setting in Low- and Middle- Income Countries
The European Union and personalised cancer medicine
(EJC, 2021)
By John Hickman, Ian Tannock, Lisa Hutchinson and Lydie Meheus
This paper discusses two recent policy documents by the European Union, ‘Europe’s Beating Cancer Plan’ and its accompanying ‘Conquering Cancer: Mission Possible’. These articulate broad policies aimed at reducing cancer mortality across Europe. The focus for cancer treatment in these manifestos is the expansion of personalised cancer medicine (PCM). We address the limits of PCM in pathology-driven and pathology-agnostic PCM, briefly discussing the results of umbrella and basket trials. We suggest that the complexity, plasticity and genetic heterogeneity of advanced cancers will continue to thwart the impact of PCM, limiting it to specific pathologies, or rare subsets of them, and that caution regarding the advancement of PCM is justified. Policymakers should be wary of the hype of lobbyists, who do not acknowledge the limits of PCM.
Blockchain’s potential to improve clinical trials
(BMJ, 2019)
“Blockchain” has become a buzzword. Some entrepreneurs and researchers evangelise its promise of innovation, but others are turned off by the hype surrounding the technology. Blockchain sceptics warn about high costs. There’s more to this tamperproof technology than bitcoin. It could be used to improve the administration of clinical trials, ensuring transparency and yielding better quality data. Patients taking part in clinical trials deserve every record to be counted, appropriately handled, and independently assessed. Increased transparency and data integrity would help to accomplish this. The remit of regulators and the funders of non-commercial research is to protect and advance public health—and therefore they, rather than industry or academia, should lead blockchain’s implementation in managing clinical trials.
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Limits to Personalized Cancer Medicine
(NEJM, 2016)
By John Hickman and Ian Tannock
This commentary addresses some of the reasons for the limited impact of cancer drugs targeted to the genetic lesions driving malignancies. The genetic heterogeneity of advanced cancers is a particular barrier to the effective use of single targeted therapies because there are multiple genetic drivers. The paper reviews some of the data on the use of drug combinations that attempt to overcome the challenge of genetic heterogeneity, suggesting that drug combinations are limited by significant host toxicity. In particular, the paper questions the growing use of targeted drugs guided by the next generation sequencing of tumour genomes, in so-called precision or personalised medicine trials. It asks that this approach is only taken as part of well-controlled trials and that patients should be informed of the limits of personalised cancer medicine with targeted therapies.