We describe a novel collaboration between academia and industry, an in-house data science and artificial intelligence challenge held by Novartis to develop machine-learning models for predicting drug-development outcomes, building upon research at MIT using data from Informa as the starting point. With over 50 crossfunctional teams from 25 Novartis offices around the world participating in the challenge, the domain expertise of these Novartis researchers was leveraged to create predictive models with greater sophistication. Ultimately, two winning teams developed models that outperformed the baseline MIT model—areas under the curve of 0.88 and 0.84 versus 0.78, respectively—through state-of-the-art machine-learning algorithms and the use of newly incorporated features and data. In addition to validating the variables shown to be associated with drug approval in the earlier MIT study, the challenge also provided new insights into the drivers of drug-development success and failure.

We represent risk factors as sums of orthogonal components capturing fluctuations with cycles of different length. The representation leads to novel spectral factor models in which systematic risk is allowed—without being forced—to vary across frequencies. Frequency- specific systematic risk is captured by a notion of spectral beta. We show that traditional factor models restrict the spectral betas to be constant across frequencies. The restriction can hide horizon-specific pricing effects that spectral factor models are designed to re- veal. We illustrate how the methods may lead to economically meaningful dimensionality reduction in the factor space.

The 75th anniversary of the founding of the Financial Analysts Journal offers a rare vista of the evolutionary path of financial analysis and its practitioners. That path is by no means random but is shaped by a complex ecosystem in which technological innovation interacts with shifting business conditions and a growing population of financial stakeholders. Using the lens of the Adaptive Markets Hypothesis—the principles of evolutionary biology and ecology applied to the financial system—we can clearly identify eight discrete financial “eras” in which unique combinations of economic need and technological advances gave rise to new products, services, and financial institutions. By understanding the underlying drivers and resulting dynamics of these eras, we can begin to develop a deeper appreciation for the origins of financial innovation and its great promise for our future.

We collect tax return data from all 311,222 public NPOs in the United States over the 2009-2017 period to study the asset allocation choices and investment returns of their endowment funds. One in nine public NPOs have endowment funds. The majority of funds allocate their assets conservatively to low-risk assets, and as a result, earn an average annual return of 5.3%. There is substantial heterogeneity in investment returns across funds. Large funds significantly outperform small funds across all return measures and nonprofit sectors. Endowments in NPO sectors devoted to public and societal benefit, the environment, and the arts are among the top performers. High returns among higher education endowments are explained by size, while hospital endowments significantly underperform. Higher investment returns are associated with better governance, more highly paid management, lower discretionary spending, and lower investment management fees. Lastly, when faced with volatile contributions, endowment funds hold more cash and invest more conservatively.

BACKGROUND: Parkinson’s disease (PD) is neurodegenerative, causing motor, cognitive, psychological, somatic, and autonomic symptoms. Understanding PD patients’ preferences for novel neurostimulation devices may help ensure that devices are delivered in a timely manner with the appropriate level of evidence. Our objective was to elicit preferences and willingness-to-wait for novel neurostimulation devices among PD patients to inform a model of optimal trial design.

METHODS: We developed and administered a survey to PD patients to quantify the maximum levels of risks that patients would accept to achieve potential benefits of a neurostimulation device. Threshold technique was used to quantify patients’ risk thresholds for new or worsening depression or anxiety, brain bleed, or death in exchange for improvements in “on-time,” motor symptoms, pain, cognition, and pill burden. The survey elicited patients’ willingness to wait to receive treatment benefit. Patients were recruited through Fox Insight, an online PD observational study.

RESULTS: A total of 2740 patients were included and a majority were White (94.6%) and had a 4-year college degree (69.8%). Risk thresholds increased as benefits increased. Threshold for depression or anxiety was substantially higher than threshold for brain bleed or death. Patient age, ambulation, and prior neurostimulation experience influenced risk tolerance. Patients were willing to wait an average of 4 to 13 years for devices that provide different levels of benefit.

CONCLUSIONS: PD patients are willing to accept substantial risks to improve symptoms. Preferences are heterogeneous and depend on treatment benefit and patient characteristics. The results of this study may be useful in informing review of device applications and other regulatory decisions and will be input into a model of optimal trial design for neurostimulation devices.

Funding for early-stage biomedical innovation has become more difficult to secure at the same time that medical breakthroughs seem to be occurring at ever increasing rates. One explanation for this counterintuitive trend is that increasing scientific knowledge can actually lead to greater economic risk for investors in the life sciences. While the Human Genome Project, high-throughput screening, genetic biomarkers, immunotherapies, and gene therapies have made a tremendously positive impact on biomedical research and, consequently, patient lives, they have also increased the cost and complexity of the drug development process, causing many investors to shift their assets to more attractive investment opportunities. This suggests that new business models and financing strategies can be used to reduce the risk and increase the attractiveness of biomedical innovation so as to bring new and better therapies to patients faster.

Bayes' rule is a fundamental principle that has been applied across multiple disciplines. However, few studies have addressed its origin as a cognitive strategy or the underlying basis for generalization from a small sample. Using a simple binary choice model subject to natural selection, we derive Bayesian inference as an adaptive behavior under certain stochastic environments. Such behavior emerges purely through the forces of evolution, despite the fact that our population consists of mindless individuals without any ability to reason, act strategically, or accurately encode or infer environmental states probabilistically. In addition, three specific environments favor the emergence of finite memory—those that are Markov, nonstationary, and environments where sampling contains too little or too much information about local conditions. These results provide an explanation for several known phenomena in human cognition, including deviations from the optimal Bayesian strategy and finite memory beyond resource constraints.

Probability matching, also known as the “matching law” or Herrnstein’s Law, has long puzzled economists and psychologists because of its apparent inconsistency with basic self-interest. We conduct an experiment with real monetary payoffs in which each participant plays a computer game to guess the outcome of a binary lottery. In addition to finding strong evidence for probability matching, we document different tendencies towards randomization in different payoff environments—as predicted by models of the evolutionary origin of probability matching—after controlling for a wide range of demographic and socioeconomic variables. We also find several individual differences in the tendency to maximize or randomize, correlated with wealth and other socioeconomic factors. In particular, subjects who have taken probability and statistics classes and those who self-reported finding a pattern in the game are found to have randomized more, contrary to the common wisdom that those with better understanding of probabilistic reasoning are more likely to be rational economic maximizers. Our results provide experimental evidence that individuals—even those with experience in probability and investing—engage in randomized behavior and probability matching, underscoring the role of the environment as a driver of behavioral anomalies.

This special issue of PNAS is intended to highlight this relatively new interdisciplinary field, featuring original joint research from collaborating biologists and financial economists on the interplay between evolutionary theory and market dynamics. The aim of this research is not to debunk traditional financial theories, but rather to complement existing research and attempt to reconcile the apparent gap between theoretical ideals and empirical realities. Given that financial economics is based so heavily on empirical observation, the synergies with evolutionary theory—which emerged from Charles Darwin’s careful study of Galápagos flora and fauna and other studies—run deep. This program is intended to improve our models rather than simply assume away or ignore the apparent inefficiencies and irrationality contained in financial data. The application of principles and techniques from evolutionary biology and associated disciplines, like ethology and ecology, may provide a key to unlocking long-standing puzzles within these disciplines. Our goal in publishing this special issue is to disseminate these ideas to a broader audience, and to encourage greater collaboration among ecologists, economists, evolutionary biologists, regulators, and finance professionals.

Development of curative treatments for glioblastoma (GBM) has been stagnant in recent decades largely because of significant financial risks. A portfolio-based strategy for the parallel discovery of breakthrough therapies can effectively reduce the financial risks of potentially transformative clinical trials for GBM. Using estimates from domain experts at the National Brain Tumor Society (NBTS), we analyze the performance of a portfolio of 20 assets being developed for GBM, diversified across different development phases and therapeutic mechanisms. We find that the portfolio generates a 14.9% expected annualized rate of return. By incorporating the adaptive trial platform GBM AGILE in our simulations, we show that at least one drug candidate in the portfolio will receive US Food and Drug Administration (FDA) approval with a probability of 79.0% in the next decade.

We construct an evolutionary model of a population consisting of two types of interacting individuals that reproduce under random environmental conditions. We show that not only does the evolutionarily dominant behavior maximize the number of offspring of each type, it also minimizes the correlation between the number of offspring of each type, driving it toward −1. We provide several examples that illustrate how correlation can be used to explain the evolution of cooperation.

The regulatory process for market authorization of medical diagnostic and therapeutic products is fraught with ethical dilemmas that regulators outside the medical industry do not face. The consequences of approving an ineffective therapy with potentially dangerous side effects (a “Type I error” or false positive) must be weighed against not approving a safe and effective therapy (a “Type II error” or false negative) that could help ease the burden of disease for many patients. Regulators must strike the proper balance by considering multiple factors, including scientific merit; clinical evidence from randomized, control trials; the burden of disease; the current standard of care and alternatives; and patient preferences. How these factors are—and should be—weighed is not always clear, which only encourages criticism by whichever stakeholder group disagrees with the decision.

Academic institutions play a central role in the biotech industry through technology licensing and the creation of startups, but few data are available on their performance and the magnitude of their impact. Here we present a systematic study of technology licensing by one such institution, the Massachusetts Institute of Technology (MIT). Using data on the 76 therapeutics-focused life sciences companies formed through MIT’s Technology Licensing Office from 1983 to 2017, we construct several measures of impact, including MIT patents cited in the Orange Book, capital raised, outcomes from mergers and acquisitions, patents granted to MIT intellectual property licensees, drug candidates discovered and US drug approvals—a key benchmark of innovation in the biopharmaceutical industry. As of December 2017, Orange Book listings for four approved small-molecule drugs cite MIT patents, but another 31 FDA-approved drugs (excluding candidates acquired after phase 3) had some involvement of MIT licensees. Fifty-five percent of the latter were either a new molecular entity or a new biological entity, and 55% were granted priority review, an indication that they address an unmet medical need. The methodology described here may be a useful framework for other academic institutions to track outcomes of intellectual property in the therapeutics domain.

We propose a heuristic approach to modeling investor behavior by simulating combinations of simpler systematic investment strategies associated with well-known behavioral biases—in functional forms motivated by an extensive review of the behavioral finance literature—using parameters calibrated from historical data. We compute the investment performance of these heuristics individually and in pairwise combinations using both simulated and historical asset-class returns. The mean-reversion or momentum nature of a heuristic can often explain its effect on performance, depending on whether asset returns are consistent with such dynamics. These algorithms show that seemingly irrational investor behavior may, in fact, have been shaped by evolutionary forces and can be effective in certain environments and maladaptive in others.

Current brain research, innovation, regulatory, and funding systems are artificially siloed, creating boundaries in our understanding of the brain based on constructs such as aging, mental health, and/or neurology, when these systems are all inextricably integral.

Grand strategy provides a broad framework that helps to guide all elements of a major, long-term project. There are converging global trends resulting from the COVID pandemic compelling a Brain Capital Grand Strategy: widespread appreciation of the rise in brain health issues (e.g., increase prevalence of mental illness and high rates of persons with age-related cognitive impairment contracting COVID), increased automation, job loss and underemployment, radical restructuring of health systems, rapid consumer adoption and acceptance of digital and remote solutions, and recognition of the need for economic reimagination. If we respond constructively to this crisis, the COVID pandemic could catalyze institutional change and a better social contract.