Clinical trial protocols become overly complex because teams copy and paste from previous studies, accumulating unnecessary data points and criteria. Merck advocates for "protocol lean design," which starts from the core research question and rigorously challenges every data collection point to reduce site and patient burden.

Novo Nordisk ran a nearly 4,000-patient Phase 3 Alzheimer's trial despite publicly stating it had a low probability of success. This strategy consumes valuable patient resources, raising ethical questions about whether a smaller, definitive Phase 2 study would have been a more responsible approach for the broader research ecosystem.

The most valuable lessons in clinical trial design come from understanding what went wrong. By analyzing the protocols of failed studies, researchers can identify hidden biases, flawed methodologies, and uncontrolled variables, learning precisely what to avoid in their own work.

Don't dismiss high-leverage but hard-to-measure interventions like government capacity building. Use "cost-effectiveness thinking": create back-of-the-envelope calculations and estimate success probabilities. This imposes quantitative discipline on qualitative decisions, avoiding the streetlight effect of only focusing on what's easily measured.

Government-administered aid programs are often highly inefficient, with significant overhead costs meaning only "cents on the dollar" reach the intended recipients. A more effective solution is to provide direct cash transfers or vouchers, empowering individuals to spend the money within the existing private market.

When a public health intervention successfully prevents a crisis, the lack of a negative outcome makes the initial action seem like an unnecessary overreaction. This paradox makes it difficult to justify and maintain funding for preventative measures whose success is invisible.

While cash transfers are effective, the "Graduation Model" provides a more comprehensive intervention. It bundles a cash or asset transfer with training, life coaching, and savings access to build stable, long-term income sources for the ultra-poor, showing more consistent long-run effects across dozens of RCTs.

For any development problem, a program should either be based on strong existing evidence ("use it") or, if such evidence is absent, be designed as an experiment to generate new findings ("produce it"). This simple mantra avoids redundant research and ensures all spending either helps or learns.

A charity like Make-A-Wish can demonstrably create value, even exceeding its costs in healthcare savings. However, the same donation could save multiple lives elsewhere, illustrating the stark opportunity costs in charitable giving. Effective philanthropy requires comparing good options, not just identifying them.