Andrew Lo discusses the tension between statistical significance (p-values) and patient values in medical research. Based on his research, he proposes a Bayesian decision analysis framework for making regulatory decisions that reflects differences in both the impact of diseases and stakeholder perspectives in a systematic, objective, transparent and repeatable manner.

For precision genetic medicines to fulfill their potential as treatments for ultra-rare diseases, fresh approaches to academic– industry partnerships and data sharing are needed, together with regulatory change and adaptation of reimbursement models. Advances in gene therapy and gene editing technologies could revolutionize the ability to treat individuals with genetic disease, allowing treatments to be devised that target specific genetic mutations in people with even the rarest of disease indications. In 2018, a seven-year-old child with Batten disease received attention for becoming the first recipient of a customized antisense oligonucleotide (ASO) therapy specifically designed for her unique mutation1. Since then, multiple patients with ultra-rare genetic conditions have been treated with precision ASOs through academic-investigator-initiated programs. Development of these ASOs has been rapid, justified by the severity of the conditions being treated (for example, rapidly progressive neurologic degeneration), following streamlined regulatory processes. Here we discuss possible models for drug development, regulation and reimbursement that could allow these tailored genetic interventions to be scaled.

Most people will experience a severe pandemic within their lifetime, and the world remains dangerously unprepared. In fact, scientists predict a nearly 50% chance—the same probability as flipping heads or tails on a coin—that we will endure another COVID-19-level pandemic within the next 25 years. Shifting America’s pandemic response capability from reactive to proactive is, therefore, urgent. Failure to do so risks the country’s welfare.

Getting ahead of the next pandemic is impossible without government financing. Vaccine production is costly, and these expenses will hinder industries from preemptively developing the tools needed to halt disease transmission. For example, the total expected revenues over a 20-year vaccine patent lifecycle would cover just half of the upfront research and development (R&D) costs.

However, research suggests that a portfolio-based approach to vaccine development—especially now with new, broadly applicable mRNA technology—dramatically increases the returns on investment while also guarding against an estimated 31 of the next 45 epidemic outbreaks. With lessons learned from Operation Warp Speed, Congress can deploy this approach by (i) authorizing and appropriating $10 billion to the Biomedical Advanced Research and Development Authority (BARDA) (ii) developing a vaccine portfolio for 10 emerging infectious diseases (EIDs), and (iii) a White House Office of Science and Technology Policy (OSTP)-led interagency effort focused on scaling up production of priority vaccines.

Brains are the indispensable drivers of human progress, but brain health issues can wreak havoc on society. Consider the devastation of disorders like depression, anxiety, and Alzheimer disease—which cost the economy trillions each year. There are currently $40.5 trillion allocated to Environment, Sustainability, and Governance (ESG) investing around the world. If only a portion of these funds were diverted into brain health, they could produce major improvements for our society.

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.

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.

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.

Opinion article by Andrew W. Lo and Kenneth Kosik on the potential role of California in the space of Alzheimer's Disease research.

Ever since I was a graduate student in economics, I’ve been struggling with the uncomfortable observation that economic theories often don’t seem to work in practice. That goes for that most influential economic theory, the Efficient Markets Hypothesis, which holds that investors are rational decision makers and market prices fully reflect all available information, that is, the “wisdom of crowds.”