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.

While the FDA is often blamed for high trial costs, a major culprit is the consolidated Clinical Research Organization (CRO) market. These entrenched players lack incentives to adopt modern, cost-saving technologies, creating a structural bottleneck that prevents regulatory modernization from translating into cheaper and faster trials.

When integrating acquired biotechs, Merck prioritizes retaining key talent and preserving ongoing science. The strategy involves immediate face-to-face engagement to reduce anxiety, followed by a pragmatic assessment of which processes must be standardized versus which can remain to avoid disrupting critical trials, a practice they call avoiding 'mercification'.

Novo Nordisk's large semaglutide Alzheimer's trial failure highlights a critical design flaw: launching a massive study without first using smaller trials to validate mechanistic biomarkers and confirm central nervous system penetration. This serves as a cautionary tale for all CNS drug developers.

Despite a threefold increase in data collection over the last decade, the methods for cleaning and reconciling that data remain antiquated. Teams apply old, manual techniques to massive new datasets, creating major inefficiencies. The solution lies in applying automation and modern technology to data quality control, rather than throwing more people at the problem.

Using safety and preliminary efficacy data from its lead drug for MPS1, Immusoft successfully requested an FDA waiver for definitive toxicology studies for its next program in MPS2. This platform approach saves significant time and capital, accelerating the entire pipeline without 'reinventing the wheel'.

Clinical trial sites are increasingly leveraging their power to demand protocol modernization from sponsors. Merck changed its internal processes to allow non-physician sub-investigators only after a site refused to participate without that flexibility. This shows that operational change can be driven from the ground up by partners, not just top-down by sponsors.

Modernizing trials is less about new tools and more about adopting a risk-proportional mindset, as outlined in ICH E6(R3) guidelines. This involves focusing rigorous oversight on critical data and processes while applying lighter, more automated checks elsewhere, breaking the industry's habit of treating all data with the same level of manual scrutiny.

Merck uses a functional service provider (FSP) model, integrating CRO staff directly into their teams. They follow Merck processes and use Merck systems, creating a seamless experience for trial sites and avoiding the transactional conflicts and change orders common in fully outsourced models, which allows for greater agility.