Key Points Question What is the estimated percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor drugs approved for oncology indications by the US Food and Drug Administration? Findings This cross-sectional study found that the estimated percentage of US patients with cancer who are eligible for checkpoint inhibitor drugs increased from 1.54% in 2011 to 43.63% in 2018. The percentage of patients estimated to respond to checkpoint inhibitor drugs was 0.14% in 2011 and increased to 12.46% in 2018. Meaning The estimated percentages of patients who are eligible for and who respond to checkpoint inhibitor drugs are higher than reported estimates for drugs approved for genome-driven oncology but remain modest.

IMPORTANCE A common justification for high cancer drug prices is the sizable research and development (R&D) outlay necessary to bring a drug to the US market. A recent estimate of R&D spending is $2.7 billion (2017 US dollars). However, this analysis lacks transparency and independent replication. OBJECTIVE To provide a contemporary estimate of R&D spending to develop cancer drugs. DESIGN, SETTING, AND PARTICIPANTS Analysis of US Securities and Exchange Commission filings for drug companies with no drugs on the US market that received approval by the US Food and Drug Administration for a cancer drug from January 1, 2006, through December 31, 2015. Cumulative R&D spending was estimated from initiation of drug development activity to date of approval. Earnings were also identified from the time of approval to the present. The study was conducted from December 10, 2016, to March 2, 2017. MAIN OUTCOMES AND MEASURES Median R&D spending on cancer drug development.RESULTS Ten companies and drugs were included in this analysis. The 10 companies had a median time to develop a drug of 7.3 years (range, 5.8-15.2 years). Five drugs (50%) received accelerated approval from the US Food and Drug Administration, and 5 (50%) received regular approval.

Although the number of patients eligible for genome-driven treatment has increased over time, these drugs have helped a minority of patients with advanced cancer. To accelerate progress in precision oncology, novel trial designs of genomic therapies should be developed, and broad portfolios of drug development, including immunotherapeutic and cytotoxic approaches, should be pursued.

Internet technology is often considered to be fundamentally changing the business paradigm and increasingly integrated into the marketing function. The authors offer a conceptual model linking market orientation, marketing competencies, and export performance and investigate the role of the Internet technology in these relationships. On the basis of an analysis of survey data from 381 manufacturing firms involved in exporting, the authors find that firms' integration of Internet technology into marketing activities generally leverages the influence of market orientation on the firms' marketing competencies (compared with competitors), which in turn have a positive impact on their export performance. The authors identify competitive intensity, firm size, and degree of export dependence as additional moderating variables.Notes: Values in the cells are marketing competencies measured on a 1-5 scale (1 = "well below industry average," 5 = "well above industry average"). at the University of Wisconsin-Madison.

BackgroundSurrogate outcomes are not intrinsically beneficial to patients, but are designed to be easier and faster to measure than clinically meaningful outcomes. The use of surrogates as an endpoint in clinical trials and basis for regulatory approval is common, and frequently exceeds the guidance given by regulatory bodies.DiscussionIn this article, we demonstrate that the use of surrogates in oncology is widespread and increasing. At the same time, the strength of association between the surrogates used and clinically meaningful outcomes is often unknown or weak. 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. Post-marketing studies, designed to ensure drugs have meaningful benefits, are often not performed. Alternatively, if a drug fails to improve quality of life or overall survival, market authorization is rarely revoked.We suggest this reliance on surrogates, and the imprecision surrounding their acceptable use, means that numerous drugs are now approved based on small yet statistically significant increases in surrogates of questionable reliability. In turn, this means the benefits of many approved drugs are uncertain. This is an unacceptable situation for patients and professionals, as prior experience has shown that such uncertainty can be associated with significant harm.ConclusionThe use of surrogate outcomes should be limited to situations where a surrogate has demonstrated robust ability to predict meaningful benefits, or where cases are dire, rare or with few treatment options. In both cases, surrogates must be used only when continuing studies examining hard endpoints have been fully recruited.