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The Alzheimer's disease (AD) research field has entered a new era, where our fundamental understanding of the pathophysiology of AD and advances in biomarkers have not only allowed for earlier, timely, and accurate detection and diagnosis of the disease, but that amyloid removal has been shown to be associated with signals of slowing cognitive and functional decline. Although recent FDA‐approved amyloid plaque‐lowering monoclonal antibody therapies have shifted the trajectory of AD, additional treatment options will be key to further slowing clinical decline or stopping disease progression. Thus, new and emerging therapies for AD have created an evolving therapeutic landscape. The Alzheimer's Association Research Roundtable (AARR) Spring meeting held on May 23–34, 2023, brought together a broad array of scientific leaders from the AARR membership, academia, industry, and government and regulatory agencies to discuss the future of clinical trials in an era of regulator‐approved amyloid‐targeting therapies. Participants discussed lessons learned from other neurological diseases where disease‐modifying treatments were first approved and key considerations for future clinical trials, for example, trial population real‐world representativeness, duration, biomarker screening, efficacy endpoints, combination therapy, as well as overall trial design and the ethical and equity concerns that clinicians, patients, and their families face when considering clinical trial participation. Highlights The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry and academia, as well as patients, clinicians, and government and regulatory agency scientists to discuss the topic, “Alzheimer's Disease Drug Development in an Evolving Therapeutic Landscape.” While recently approved amyloid‐targeting therapies show great promise in providing clinically meaningful outcomes for patients and families, additional treatments, and a better understanding of dosing and administration of these approved treatments, are needed to further slow and eventually prevent clinical decline in AD. Approved therapies will impact many aspects of clinical trial design including the use of placebo‐controls, participant re‐enrollment, safety monitoring, as well as biomarker selection. This exciting new era in AD research represents a hopeful future for clinicians, patients, and their care partners.

We conducted an experimental intervention in unelectrified areas of northern Bangladesh to investigate the effectiveness of solar products in improving children’s educational achievement. We found that treated households substituted solar lanterns for kerosene-based lighting products, helping to decrease total household expenditure. Solar lanterns increased the children’s home-study hours, particularly at night and before exams. The solar lanterns initially led to an increase in school attendance, but this effect diminished over time. However, the increased study hours and initial improvement in school attendance did not translate into improved academic performance. Varying the number of solar products within the treated households did not alter these results. Analyses that exploited the school grade treatment intensity also provided no evidence suggesting that spillover effects explained the “no academic performance effects.” These findings suggest that improving the home-study environment solely through the provision of solar products may have a limited impact on children’s educational achievement.

This paper measures the causal effects of parent enrollment into voluntary health insurance on healthcare utilization among insured and uninsured children in Nicaragua. The study utilizes a randomized trial and age-eligibility cutoff in which insurance subsidies were randomly allocated to parents that covered their dependent children under 12; children age 12 and older were not eligible for coverage. Among eligible children, the insurance increased utilization at covered providers by 0.56 visits and increased overall utilization by 1.3 visits. Ineligible children with insured parents experienced 1.7 fewer healthcare visits driven by parent, not sibling, enrollment. The results suggest complementarities across healthcare provider type and provide evidence that households reallocate resources across all members in response to changes in healthcare prices for some.

Background: Recent studies have demonstrated that brain activities using NIRS (near-infrared spectroscopy) at baseline during cognitive tasks (e.g., N-back task) can predict the cognitive benefits of a cognitive training. In this study, we investigated whether brain activities during brain training game (BT) at baseline would predict benefits to cognitive functions after the intervention period. Methods: In a four-week double-blinded randomized control trial (RCT) 72 young adults were randomly assigned to one of the two groups: participants in the BT group played specific game, called the Brain Age. Participants in an active control group (ACT) played the puzzle game Tetris. We measured brain activity during the training games using two channel NIRS before the intervention period. Cognitive functions were tested before and after the four-week intervention period. Results: The BT showed significant improvements in inhibition, processing speed, and working memory performance compared to ACT. The left and right DLPFC (dorsolateral prefrontal cortex) brain activities during the BT at baseline were associated with improvements in inhibition and processing speed. Discussion: This randomized control trial first provides scientific evidence that DLPFC activities during BT at baseline can predict cognitive improvements after a four-week intervention period.

We conducted an experimental intervention in unelectrified areas of northern Bangladesh to investigate the effectiveness of solar products in improving children’s educational achievement. We found that treated households substituted solar lanterns for kerosene-based lighting products, helping to decrease total household expenditure. Solar lanterns increased the children’s home-study hours, particularly at night and before exams. The solar lanterns initially led to an increase in school attendance, but this effect diminished over time. However, the increased study hours and initial improvement in school attendance did not translate into improved academic performance. Varying the number of solar products within the treated households did not alter these results. Analyses that exploited the school grade treatment intensity also provided no evidence suggesting that spillover effects explained the “no academic performance effects.” These findings suggest that improving the home-study environment solely through the provision of solar products may have a limited impact on children’s educational achievement.

Abstract Three recent randomized control trials (RCTs) found that treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) did not reduce rates of future cardiovascular events. This article discusses the biases in these RCTs that may explain their negative results, and how to overcome these biases in future studies. First, sample selection bias affected each RCT. The subjects recruited were not patients typically presenting for treatment of OSA. In particular, subjects with excessive sleepiness were excluded due to ethical concerns. As recent data indicate that the excessively sleepy OSA subtype has increased cardiovascular risk, subjects most likely to benefit from treatment were excluded. Second, RCTs had low adherence to therapy. Reported adherence is lower than found clinically, suggesting it is in part related to selection bias. Each RCT showed a CPAP benefit consistent with epidemiological studies when restricting to adherent patients, but was underpowered. Future studies need to include sleepy individuals and maximize adherence. Since it is unethical and impractical to randomize very sleepy subjects to no therapy, alternative designs are required. Observational designs using propensity scores, which are accepted by FDA for studies of medical devices, provide an opportunity. The design needs to ensure covariate balance, including measures assessing healthy user and healthy adherer biases, between regular users of CPAP and non-users. Sensitivity analyses can evaluate the robustness of results to unmeasured confounding, thereby improving confidence in conclusions. Thus, these designs can robustly assess the cardiovascular benefit of CPAP in real-world patients, overcoming biases in RCTs.

(1) Background: The aim of this study was to pool and compare all-cause and colorectal cancer (CRC) specific mortality reduction of CRC screening in randomized control trials (RCTs) and simulation models, and to determine factors that influence screening effectiveness. (2) Methods: PubMed, Embase, Web of Science and Cochrane library were searched for eligible studies. Multi-use simulation models or RCTs that compared the mortality of CRC screening with no screening in general population were included. CRC-specific and all-cause mortality rate ratios and 95% confidence intervals were calculated by a bivariate random model. (3) Results: 10 RCTs and 47 model studies were retrieved. The pooled CRC-specific mortality rate ratios in RCTs were 0.88 (0.80, 0.96) and 0.76 (0.68, 0.84) for guaiac-based fecal occult blood tests (gFOBT) and single flexible sigmoidoscopy (FS) screening, respectively. For the model studies, the rate ratios were 0.45 (0.39, 0.51) for biennial fecal immunochemical tests (FIT), 0.31 (0.28, 0.34) for biennial gFOBT, 0.61 (0.53, 0.72) for single FS, 0.27 (0.21, 0.35) for 10-yearly colonoscopy, and 0.35 (0.29, 0.42) for 5-yearly FS. The CRC-specific mortality reduction of gFOBT increased with higher adherence in both studies (RCT: 0.78 (0.68, 0.89) vs. 0.92 (0.87, 0.98), model: 0.30 (0.28, 0.33) vs. 0.92 (0.51, 1.63)). Model studies showed a 0.62–1.1% all-cause mortality reduction with single FS screening. (4) Conclusions: Based on RCTs and model studies, biennial FIT/gFOBT, single and 5-yearly FS, and 10-yearly colonoscopy screening significantly reduces CRC-specific mortality. The model estimates are much higher than in RCTs, because the simulated biennial gFOBT assumes higher adherence. The effectiveness of screening increases at younger screening initiation ages and higher adherences.

Early childhood poverty is a risk factor for lower school achievement, reduced earnings, and poorer health, and has been associated with differences in brain structure and function. Whether poverty causes differences in neurodevelopment, or is merely associated with factors that cause such differences, remains unclear. Here, we report estimates of the causal impact of a poverty reduction intervention on brain activity in the first year of life. We draw data from a subsample of the Baby’s First Years study, which recruited 1,000 diverse low-income mother–infant dyads. Shortly after giving birth, mothers were randomized to receive either a large or nominal monthly unconditional cash gift. Infant brain activity was assessed at approximately 1 y of age in the child’s home, using resting electroencephalography (EEG; n = 435). We hypothesized that infants in the high-cash gift group would have greater EEG power in the mid- to high-frequency bands and reduced power in a low-frequency band compared with infants in the low-cash gift group. Indeed, infants in the high-cash gift group showed more power in high-frequency bands. Effect sizes were similar in magnitude to many scalable education interventions, although the significance of estimates varied with the analytic specification. In sum, using a rigorous randomized design, we provide evidence that giving monthly unconditional cash transfers to mothers experiencing poverty in the first year of their children’s lives may change infant brain activity. Such changes reflect neuroplasticity and environmental adaptation and display a pattern that has been associated with the development of subsequent cognitive skills.

Background and objectives: The purpose of this study is to clarify the effects on the mental health of face-to-face exercise performed by an instructor (lesson-style Group: Group L) and exercise using machines (program-style Group: Group P) by randomized control trial. Materials and Methods: Among 120 subjects, 117 subjects were allocated to two groups with stratified randomization by sex (Group P: 58 subjects; Group L: 59 subjects). A 60-min health exercise class was held once per week for 12 consecutive weeks. The measurement items were mental health as a primary evaluation item and self-efficacy as a secondary evaluation item. Physical fitness was also measured using a new physical fitness test used in Japan. The 12-item general health questionnaire (GHQ-12) was used to measure mental health and the general self-efficacy scale (GSES) was used to measure self-efficacy. Results: After the intervention, 102 subjects were analyzed. The changes in mental health evaluated by GHQ-12 scores were significantly lower in Group L −0.7 (95% CI, −1.2 to −0.3) than Group P −0.1 (95% CI, −0.4 to 0.2) (p = 0.03). The changes in self-efficacy evaluated by GSES scores were significantly higher in Group P 5.3 (95% CI, 3.1 to 7.5) than Group L 1.3 (95% CI, −0.4 to 3.1) (p < 0.01). Conclusions: Compared with program exercises mainly using machines, face-to-face exercises performed by instructors improved mental health.

A classical approach to collecting and elaborating information to make entrepreneurial decisions combines search heuristics, such as trial and error, effectuation, and confirmatory search. This paper develops a framework for exploring the implications of a more scientific approach to entrepreneurial decision making. The panel sample of our randomized control trial includes 116 Italian startups and 16 data points over a period of about one year. Both the treatment and control groups receive 10 sessions of general training on how to obtain feedback from the market and gauge the feasibility of their idea. We teach the treated startups to develop frameworks for predicting the performance of their idea and conduct rigorous tests of their hypotheses, very much as scientists do in their research. We let the firms in the control group instead follow their intuitions about how to assess their idea, which has typically produced fairly standard search heuristics. We find that entrepreneurs who behave like scientists perform better, are more likely to pivot to a different idea, and are not more likely to drop out than the control group in the early stages of the startup. These results are consistent with the main prediction of our theory: a scientific approach improves precision—it reduces the odds of pursuing projects with false positive returns and increases the odds of pursuing projects with false negative returns. This paper was accepted by Marie Thursby, entrepreneurship and innovation.