Delivering the precision oncology paradigm: reduced R&D costs and greater return on investment through a companion diagnostic informed precision oncology medicines approach.

BACKGROUND: Precision oncology medicines represent a paradigm shift compared to non-precision oncology medicines in cancer therapy, in some situations delivering more clinical benefit, and potentially lowering healthcare costs. We determined whether employing a companion diagnostic (CDx) approach during oncology medicines development delivers effective therapies that are within the cost constraints of current health systems. R&D costs of developing a medicine are subject to debate, with average estimates ranging from $765 million (m) to $4.6 billion (b). Our aim was to determine whether precision oncology medicines are cheaper to bring from R&D to market; a secondary goal was to determine whether precision oncology medicines have a greater return on investment (ROI). METHOD: Data on oncology medicines approved between 1997 and 2020 by the US Food and Drug Administration (FDA) were analysed from the Securities and Exchange Commission (SEC) filings. Data were compiled from 10-K, 10-Q, and 20-F financial performance filings on medicines' development costs through their R&D lifetime. Clinical trial data were split into clinical trial phases 1-3 and probability of success (POS) of trials was calculated, along with preclinical costs. Cost-of-capital (CoC) approach was applied and, if appropriate, a tax rebate was subtracted from the total. RESULTS: Data on 42 precision and 29 non-precision oncology medicines from 56 companies listed by the National Cancer Institute which had complete data available were analysed. Estimated mean cost to deliver a new oncology medicine was $4.4b (95% CI, $3.6-5.2b). Costs to bring a precision oncology medicine to market were $1.1b less ($3.5b; 95% CI, $2.7-4.5b) compared to non-precision oncology medicines ($4.6b; 95% CI, $3.5-6.1b). The key driver of costs was POS of clinical trials, accounting for a difference of $591.3 m. Additional data analysis illustrated that there was a 27% increase in return on investment (ROI) of precision oncology medicines over non-precision oncology medicines. CONCLUSION: Our results provide an accurate estimate of the R&D spend required to bring an oncology medicine to market. Deployment of a CDx at the earliest stage substantially lowers the cost associated with oncology medicines development, potentially making them available to more patients, while staying within the cost constraints of cancer health systems.

Challenges in the clinical implementation of precision medicine companion diagnostics.

INTRODUCTION: The pace of biomarker discovery has increased exponentially over the last few years, ushering in an era of precision medicine (PM) with a growing arsenal of treatments tailored to specific patient populations. To accurately identify patients, companion diagnostics (CDx) are developed and launched alongside these treatments. However, even with a timely launch of therapies and CDx tests, patients are not guaranteed optimal access to these tests because of the inefficiencies embedded within the clinical diagnostic testing landscape supporting PM. AREAS COVERED: This commentary describes implementation challenges facing CDx tests and delaying clinical uptake. We also assess the 'siloed thinking' perpetuating these challenges and propose steps toward resolution. Our research is based on published literature and findings from the Diaceutics proprietary patient testing database. EXPERT OPINION: The clinical and economic ecosystem underpinning the diagnostic journey of patients remains severely underdeveloped. Patients are denied suitable therapies because of delayed identification or failings in real-world testing deployment. Progress is needed in clinical collaborations, integrator platforms, economic value sharing, and ownership of the patient testing journey to PM. We need to consider that better precision testing will deliver an equal or greater outcome to patients than new precision treatments alone.

Examining the functional range of commercially available low-cost airborne particle sensors and consequences for monitoring of indoor air quality in residences.

Low-cost airborne particle sensors are gaining attention for monitoring human exposure to indoor particulate matter. This study aimed to establish the concentrations at which these commercially available sensors can be expected to report accurate concentrations. We exposed five types of commercial integrated devices and three types of "bare" low-cost particle sensors to a range of concentrations generated by three different sources. We propose definitions of upper and lower bounds of functional range based on the relationship between a given sensor's output and that of a reference instrument during a laboratory experiment. Experiments show that the lower bound can range from approximately 3 to 15 µg/m3 . At greater concentrations, sensor output deviates from linearity at approximately 300-3000 µg/m3 . We also conducted a simulation campaign to analyze the effect of this limitation on functional range on the accuracy of exposure readings given by these devices. We estimate that the upper bound results in minimal inaccuracy in exposure quantification, and the lower bound can result in as much as a 50% error in approximately 10% of US homes.

Conversion, correction, and International Scale standardization: results From a Multicenter External Quality Assessment Study for BCR-ABL1 testing.

CONTEXT: Monitoring BCR-ABL1 expression levels relative to clinically validated response criteria on the International Scale (IS) is vital in the optimal management of patients with chronic myeloid leukemia, yet significant variability remains across laboratories worldwide. OBJECTIVE: To assess method performance, interlaboratory precision, and different IS standardization modalities in representative laboratories performing routine BCR-ABL1 testing. DESIGN: Fifteen blinded test specimens with 5-level nominal BCR-ABL1 to ABL1 IS percentage ratios ranging from 5% to 0.0005% and 4-level secondary IS reference panels, the ARQ IS Calibrator Panels, were tested by relative quantitative polymerase chain reaction in 15 laboratories in 5 countries. Both raw and IS percentage ratios calculated by using local conversion factors (CFs) or analytic correction parameters (CPs) were collected and analyzed. RESULTS: A total of 670 valid positive results were generated. BCR-ABL1 detection was associated with variable ABL1 quality metric passing rates (P < .001) and reached at least 0.01% in 13 laboratories. Intralaboratory precision was within 2.5-fold for all sample levels combined with a relative mean difference greater than 5-fold across laboratories. International Scale accuracy was increased by using both the CF and CP standardization methods. Classification agreement for major molecular response status was 90% after CF conversion and 93% after CP correction, with precision improved by 3-fold for the CP method. CONCLUSIONS: Despite preanalytic and analytic differences between laboratories, conversion and correction are effective IS standardization methods. Validated secondary reference materials can facilitate global diffusion of the IS without the need to perform sample exchange and improve the accuracy and precision of BCR-ABL1 quantitative measurements, including at low levels of residual disease.

Monitoring of chimerism following allogeneic haematopoietic stem cell transplantation (HSCT): technical recommendations for the use of short tandem repeat (STR) based techniques, on behalf of the United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping Chimerism Working Group.

Analysis of short tandem repeats (STR) is the predominant method for post-transplant monitoring of donor engraftment. It can enable early detection of disease relapse, level of engraftment and provide useful information on the graft-versus-host disease (GVHD)/graft-versus-tumour (GVT) effect, facilitating therapeutic intervention. Harmonization and standardization of techniques and result interpretation is essential to reduce the impact of laboratory variability on both clinical management and the results of multi-centre clinical trials. However, the United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI) has highlighted significant issues inherent in STR testing that impact upon inter- and intra- laboratory variation. We present here consensus best practice guidelines and recommendations for STR chimerism testing, data interpretation and reporting that have been drawn up and agreed by a consortium of 11 UK and Eire clinical laboratories. This document uses data obtained from the UK NEQAS LI Post-Stem Cell Transplant (SCT) Chimerism Monitoring Programme.