China Investigator-Initiated Trial (IIT) Spotlight Part 1: How do China IITs differ from other trials?

Dear all,

China IITs have become an increasingly hot topic over the summer, appearing in news headlines and at the centre of conference conversations. Vivara has also received a growing number of questions on IITs.

So we thought we would share our thinking in a three-part IIT Spotlight Series:

• How do China IITs differ from other trials?
  A recap of the basics

• The Problem Isn’t “China IITs.” It’s Trials Without Quality Systems
  A review of the cases in recent media, why they failed, and what drives success in IIT

• What does the future hold?
  A readout of what we learned 100 days after 818, and what we expect for the future

We start below with the first article, and please click to subscribe to our series!

IITs bring speed and flexibility that are vastly different from IND trials

When run correctly, IITs take a fraction of the budget of an IND trial and come with significantly greater speed and flexibility, with high-quality reliable data. There is no great secret to this. It is simply the result of well-designed, targeted trials coupled with seamless operations and ‘China efficiency’. All three are important, and we will expand on the operations part in the next article.

It is worth highlighting here the ‘China efficiency’ because it is often underestimated by people outside China. Recently, a client was exploring a glioblastoma trial with ~10 patients, using a novel surgical procedure developed by their team. There were questions around how many months it would take to recruit 10 patients and whether local PIs could learn their procedure. We told them that just one of the sites in our network conducts >600 glioblastoma operations a year, and co-surgery with their own surgeon can be arranged. So the real questions are: how many patients do they want in a month, and when can their surgeon travel to Shanghai?

But an IIT isn't just an accelerated trial — it's a different study

This gets lost in most coverage, and it is worth restating.

An IND trial may look at multiple cohorts, multiple centres, multiple statistically powered endpoints, etc. An IIT could look at the same breadth and depth (IITs can include 30 – 100 patients), but more often the study has a narrower focus; single site, less patients, more targeted endpoints, CMC and preclinical potentially tailored to study requirements. The focus is a signal, positive or negative, that a development or partnering decision can turn on. It moves quickly because the focus is sharper, not because safety was sacrificed.

Regulators are different, but the principle is the same as under FDA/EMA/NMPA

IITs are regulated through the NHC and are independent of the NMPA. The core principle is the one all agencies have talked about — to create a sustainable, systematic, regulated process that accelerates translation from bench to bedside. But as is typical with China, the speed and scale of the implementation are vastly different from what we have seen in the West. Though that has also come with real execution challenges.

Historically, the NHC had no equivalent technical review capacity, and the main gatekeepers were the individual Ethics and Academic reviewers within each hospital. There were also significant gaps in regulation that required individual interpretation or experience to bridge. This resulted in considerable variance in how trials were reviewed, approved, and managed (more on this in the next article).

But that landscape has changed.

Recently, amid the numerous, perhaps politically tinted debates on both sides, the directors of CDER, CBER, CDRH and the Oncology Center of Excellence issued a joint statement on good clinical practice in foreign studies. It says plainly that many foreign institutions produce data of the highest quality, which the FDA welcomes and relies on. What it asks for is specific: that participants were protected, that conduct met GCP, that provenance is clear, and that the record can be inspected.

In almost the same week, Chinese regulators highlighted those same criteria for conducting IITs. This follows the full implementation of Order 818, which already introduces several features that we think will significantly stem lower-quality trials. This includes the formalisation of a parallel clinical research and translational application pathway, more standardised and stringent review criteria, and considerable investment to build uniformity in reviews at local hospitals.

From the regulators’ perspective, an IIT must bring significant speed without compromising safety.

So why then did we see the stories reported in recent news? What went wrong?

Stay tuned for our next article to find out.