These are further passages of the ten texts this paper read, word for word, grouped by text. The government works are in the public domain; the six articles are published under the Creative Commons Attribution 4.0 licence. The paper's reading of them is its own interpretation, and none of the passages is offered as medical advice.
21st Century Cures Act, sections 1001 and 2011
Public law of 2016, read in two sections only: the funding account and its oversight, and the precision medicine provisions.
(B) Amounts deposited.--Any amounts transferred under subparagraph (A) shall remain unavailable in the Account until such amounts are appropriated pursuant to paragraph (3).
(d) Limitations.--Notwithstanding any transfer authority authorized by this Act or any appropriations Act, any funds made available pursuant to the authorization of appropriations under subsection (b)(3) may not be used for any purpose other than a NIH Innovation Project.
the Director of NIH shall provide an update in the form of testimony and any additional reports to the respective congressional committee regarding the allocation of funding under this section or the description of the NIH Innovation Projects.
(3) applying genomic technologies, such as whole genomic sequencing, to provide data on the molecular basis of disease;
(4) consider the diversity of the cohort to ensure inclusion of a broad range of participants, including consideration of biological, social, and other determinants of health that contribute to health disparities;
(e) Report.--Not later than 1 year after the date of enactment of the 21st Century Cures Act, the Secretary shall submit a report
National Cancer Institute, Cancer Moonshot
The Institute's page on the initiative, as retrieved; the page for the Moonshot's expert panel redirects to it.
A panel of experts was convened to make research recommendations on how to best carry out the Cancer Moonshot.
Constructed a national cancer data ecosystem — the NCI Cancer Research Data Commons — to enable researchers, clinicians, and patients to contribute data and facilitate more efficient data analysis.
Conducted a retrospective analysis of patient data and biospecimens from past clinical trials to predict future patient outcomes.
Launched the NCI Telehealth Research Centers of Excellence program , aimed at determining whether the use of telehealth can improve cancer-related care and outcomes across the cancer control continuum.
National Cancer Institute, National Cancer Plan
The landing page of the plan, as retrieved.
These goals focus on transforming how cancer research is conducted and cancer care is delivered, to accelerate progress toward achieving the health-centric goals.
Focused on directly improving health outcomes, these goals describe the progress that is needed across the spectrum of people's experiences with cancer.
FDA, Project Optimus
An initiative page of the agency's oncology centre, on dose finding.
The Oncology Center of Excellence (OCE) Project Optimus is an initiative to reform the dose optimization and dose selection paradigm in oncology drug development.
Patients may be receiving these novel therapeutics for longer periods of time to maximize the benefit of a drug, which ideally includes not only longer survival but also an improved quality of life.
Provide opportunities for and encourage drug developers to meet with FDA Oncology Review Divisions early in their development programs, well before conducting trials intended for registration, to discuss dose-finding and dose optimization.
Kemp and Prasad, Surrogate endpoints in oncology
An opinion article on when measures that stand in for survival should support regulatory and clinical decisions.
The ultimate goal of all oncology drugs is to improve patient-centered endpoints.
Attempts to validate surrogates are rarely undertaken. When this is done, validation relies on only a fraction of available data, and often concludes that the surrogate is poor.
To date, no example of a surrogate validation study based on all of the relevant evidence exists.
As companies trade off speed for market share, the role of surrogates as speeding up the process may in fact slow it down or at least maintain the current pace.
These examples emphasize that poorly validated surrogate outcomes can be misleading with regards to benefit. Premature regulatory decisions can result in patients being exposed to considerable harm for no benefit.
Haslam and Prasad, Estimation of the Percentage of US Patients
A cross-sectional study estimating, as upper bounds, how many patients with cancer in the United States were eligible for and might respond to one class of drugs.
Moreover, the percentage of individuals who are eligible to receive these drugs has grown since 2014 at a faster rate than the estimated percentage of individuals who actually benefit from these drugs.
First, our study estimates but does not measure the uptake of these drugs.
Further research should be done to clarify the effectiveness of these drugs in the real world.
Hackshaw and others, Estimating the population health impact
A modelling study of adding a blood test for many cancers to recommended screening in the United States and the United Kingdom.
Adding an MCED blood test to recommended screening can potentially be an efficient strategy. Ongoing randomised studies are required for full efficacy and cost-effectiveness evaluations.
Large RCTs with long follow-up were used to evaluate previous cancer screening tests, but innovative and complementary approaches to evidence generation are needed for rapidly evolving MCED genomic tests that detect large numbers of cancers and can demonstrate stage shift and cancer-specific mortality benefits in a shorter timeframe.
Ongoing prospective studies of various MCED tests will provide more information on overdiagnosis.
All authors had full access to all the data in the study and accept responsibility to submit for publication. Three authors are employed by the funding source though this was a collaborative academic study.
Wong and others, Estimation of clinical trial success rates
An empirical study of the chances and durations of clinical drug development, from trial databases.
Previous estimates of drug development success rates rely on relatively small samples from databases curated by the pharmaceutical industry and are subject to potential selection biases.
Oncology trials have lower CRs across all phases, with only 73.9% of the trials reaching completion. This points to a possible bottleneck in the development of oncology drugs.
We found that trials using biomarkers for patient stratification have higher success rates, especially in the area of oncology. Given the active development of biomarkers for the area of oncology, we expect that the dismal approval rates of oncology will improve.
However, our expectations are tempered by the fact that the median time to completion for oncology trials is twice as long as for non-oncology trials, signifying increased cost and risk.
Sammut and others, Multi-omic machine learning predictor
A study that built a predictor of response to treatment before surgery from breast tumour biopsies and tested it on an external cohort.
However, these studies have been frequently small, combined data from patients receiving different treatments and used single platform profiling that fails to capture the complexity of the tumour ecosystem.
Combining these features into a multi-omic machine learning model predicted a pathological complete response in an external validation cohort (75 patients) with an area under the curve of 0.87.
The high accuracy obtained in external validation suggests that the models are robust and may enable using molecular and digital pathology to determine therapy choice in future clinical trials, including in the adjuvant therapy setting.
Rojas and others, Personalized RNA neoantigen vaccines
The report of an early-phase trial, in pancreatic cancer after surgery, of a vaccine made for each patient.
The primary end point was safety (Extended Data Table 1). Secondary end points were 18-month RFS and 18-month OS.
Our study was not powered to detect differences in biomarkers of vaccine response.
Furthermore, given its limited sample size, this trial enrolled only white individuals.
Future studies must test individualized mRNA neoantigen vaccines in a diverse population of patients with PDAC, coupled with a faster time to adjuvant mFOLFIRINOX.