Spectral factor models2021
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.
To maximize or randomize? An experimental study of probability matching in financial decision making2021
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.
The evolutionary origin of Bayesian heuristics and finite memory2021
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.
Can Financial Economics Cure Cancer?2021
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.
Introduction to PNAS special issue on evolutionary models of financial markets2021
One of the longest debates in economics involves the existence of a rare Hominid “species” known as Homo economicus, the economic human. H. economicus is able to determine the optimal use of its resources to maximize its well-being as defined by the assumptions of neoclassical economics, leading to behavior that has come to be known as economic rationality. When interacting with other members of this species in market settings, such behavior leads to a magical outcome. The participants’ self-interested efforts to exploit their disparate pieces of information aggregates, distills, and compresses their information into a single number: the price. And because no piece of information is left unused or uninterpreted in the process of price discovery, this market is deemed “efficient.” Prices fully reflect all available information, as Eugene Fama concluded in his first articulation of the efficient markets hypothesis (1).
The origin of cooperation2021
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.
Patterns of Multimorbidity2021
With multimorbidity becoming the norm rather than the exception, the management of multiple chronic diseases is a major challenge facing healthcare systems worldwide. Using a large, nationally representative database of electronic medical records from the United Kingdom spanning the years 2005 to 2016 and consisting over 4.5 million patients, we apply statistical methods and network analysis to identify comorbid pairs and triads of diseases and identify clusters of chronic conditions across different demographic groups. Unlike many previous studies, which generally adopt cross-sectional designs, we examine temporal changes in the patterns of multimorbidity. In addition, we perform survival analysis to examine the impact of multimorbidity on mortality.
Accelerating glioblastoma therapeutics via venture philanthropy2021
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.
Algorithmic Models of Investor Behavior2021
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.
Life sciences intellectual property licensing at the Massachusetts Institute of Technology2021
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.
Incorporating Patient Preferences via Bayesian Decision Analysis2021
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.
Parkinson’s Patients’ Tolerance for Risk and Willingness to Wait for Potential Benefits of Novel Neurostimulation Devices: A Patient-Centered Threshold Technique Study2021
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.
World of EdCraft: Challenges and Opportunities in Synchronous Online Teaching2021
Online teaching at higher educational institutions has become a much higher priority in the face of the COVID-19 pandemic, but most faculty and staff at these institutions are ill-prepared to adapt their teaching methods and content to this new medium. In this article, we describe our approach to dealing with the challenges and opportunities of synchronous online teaching by borrowing ideas and tools from the gaming community. The gamification of education is a well- known concept, but we found few applications in higher-education settings to rely on when we were forced to move online in March 2020. We hope to remedy this gap by providing colleagues with a step-by-step guide to setting up their own home studios, including a complete listing of the software and hardware that we use and how we use them in three distinct online teaching applications: a large (90-student) graduate healthcare finance course at MIT, an even larger (200- student) undergraduate statistics course at the University of Tennessee Knoxville, and a medium- sized (50-student) graduate operations management course at MIT.
Financing Correlated Drug Development Projects2021
Current business models have struggled to support early-stage drug development. In this paper, we study an alternative financing model, the megafund structure, to fund drug discovery. We extend the framework proposed in previous studies to account for correlation between phase transitions in drug development projects, thus making the model a more realistic representation of biopharma research and development. In addition, we update the parameters used in our simulation with more recent estimates of the probability of success (PoS). We find that the performance of the megafund becomes less attractive when correlation between projects is introduced. However, the risk of default and the expected returns of the vanilla megafund remain promising even under moderate levels of correlation. In addition, we find that a leveraged megafund outperforms an equity-only structure over a wide range of assumptions about correlation and PoS.
A Cost/Benefit Analysis of Clinical Trial Designs for COVID-19 Vaccine Candidates2020
We compare and contrast the expected duration and number of infections and deaths averted among several designs for clinical trials of COVID-19 vaccine candidates, including traditional and adaptive randomized clinical trials and human challenge trials. Using epidemiological models calibrated to the current pandemic, we simulate the time course of each clinical trial design for 756 unique combinations of parameters, allowing us to determine which trial design is most effective for a given scenario. A human challenge trial provides maximal net benefits—averting an additional 1.1M infections and 8,000 deaths in the U.S. compared to the next best clinical trial design—if its set-up time is short or the pandemic spreads slowly. In most of the other cases, an adaptive trial provides greater net benefits.