Targeted and Strategy-Driven Clinical Development

In a recent video interview with Applied Clinical Trials, Heidi Chen, Associate Director of Research & Commercial Services at Citeline, discussed findings from the company’s 2025 Annual Clinical Trials Roundup. She outlined how personalized and biomarker-based therapies are creating opportunities and challenges for trial design, especially in rare disease populations, and highlighted the use of historical controls and real-world evidence to support targeted development. She also explained the growth in CNS, autoimmune, and obesity trials, noting the operational implications for study design, site selection, and adoption of decentralized and hybrid trial models. Finally, she discussed how sponsors and CROs are navigating new ICH GCP guidelines while continuing to innovate and maintain data integrity, emphasizing resilience and the ongoing expansion of the clinical pipeline.

The below interview transcript was lightly edited for clarity.

ACT: With Phase I-III trial starts growing 5.5% in 2024, how would you describe the shift toward more targeted and strategy-driven clinical development?

Chen: It's a very good question and great observation. I would say that targeted and personalized therapies have certainly emerged, and it's trending, especially when you think about treatment based on biomarkers or personal genetics. You're actually creating a custom-made biological product for each patient. However, you have to keep in mind that these drugs are also limited to treating the relevant patient population, which can be kind of niche and sometimes small in certain rare diseases. So there's going to be some logistical challenge to apply these approaches toward large randomized clinical trials, as in traditional medicine.

That said, smaller, single-arm trials that are using historical controls or utilizing combinations with real-world evidence gathered from registries and medical records do offer some possibility to help progress development in these strategy-driven developments. Rare diseases and over-indication therapies are increasingly making some progress—they're making some strides, even though it's a relatively small patient pool. Given the current limitations I just mentioned, traditional drug discovery and large RCTs [randomized clinical trials] aren't going to go away or be replaced by these targeted therapies.

In general, I think there's going to be more growth, especially in clinical trials overall, because we are going to see new drugs entering the pipeline, and we keep seeing them progressing through each clinical phase. We’re also seeing a trend in early attrition, which is probably one of the important strategies occurring. The share of Phase I trials has very little change compared with last year, but Phase II had a big increase, and Phase III had the most impressive jump—it went from 2.7% to 15.4%, as pointed out in the paper. That just goes to show these are encouraging successes in drugs passing through these crucial Phase I and II hurdles.