Managing Clinical Trials

Evaluating a trial site's track record

This month we've been writing about selecting sites for phase I oncology trials.  Our first recommendation is to use a dedicated oncology team.  Then we provide pros and cons of academic versus private sites.  Now we'll move to evaluating potential sites.

Without a doubt, your direct experience with a site is the best predictor of future success. You know what type of service, results, and responsiveness to expect. But what if you haven’t worked with a site before? How do you evaluate them?

Thoroughly.

Step one:  Determine how many phase I studies the site has completed in the last 12 to 24 months. Look for the details such as the number of patients enrolled in each study, enrollment rates, and data collection.

You’re always looking for a dedicated phase I oncology team. But sometimes we’re given sites that don’t have a dedicated team, so we have to make the best with what we have.

Since phase I oncology studies typically follow a standard approach, site comparisons are pretty straightforward. Talk directly with the site’s nurse to validate her experience. If she has hands-on phase I experience, you can be more comfortable that she understands the fast-changing nature of a phase I oncology trial and will handle the curveballs that always appear. It’s a red flag a nurse isn’t familiar with the phase I oncology process or feels that certain steps or frequencies of meetings are excessive.

It’s also important to understand the investigator’s experience level. Senior investigators are great because of their experience. Inexperienced investigators might require more hands-on trial management.

Something we look out for is a senior investigator that likes to assign a junior faculty member to a study.  While the junior member might bring enthusiasm to the study and enroll patients ahead of schedule (which of course sponsors love), his/her lack of experience can sometimes lead to trial problems later on.

For instance, overshooting patient enrollment rates can backfire if the structure and site staff aren’t in place to handle the impending avalanche of data. An experienced investigator will know that pacing patients is critical for staying responsive and keeping data processing manageable.

If "over-enrollment" occurs, it can become a challenging situation for you as a sponsor. You’re excited about being ahead of schedule, which sends a positive signal to management. But you also know that the faster patients go on study, the harder it becomes to manage the future data — especially if the right site staffing infrastructure isn’t in place.

Data managers or monitors are the people that understand the volume of work involved with getting data collected, reviewed, and entered into the database. "Over-enrollment" often leads to later delays, which wipes out the previous gains and makes it difficult to continue work with that site on the next trial.

Assessing a site’s track record is important when determining if you’re going to select it for your study. It’s also important to understand what’s in store for you if the site has already been selected for your trial. Dive deep into the details. Understand the site’s true experience, the nurse’s hands-on experience level, the lead investigator, and the site’s ability to manage resources. It’s well worth it and will help you keep your trial on track and on budget.

Academic versus private sites

In our last post, we talked about the importance of having a dedicated phase I oncology team and support structure at your site. Another element to evaluate is the type of site to use — academic or private?

It’s important to match your sites to fit your protocol and trial goals. However, there are differences between academic and private centers that directly affect the success of your trial.

Academic sites

Let’s look at the academic center first. If the site is a comprehensive cancer center, it likely has a dedicated phase I team. This is great and suggests a level of expertise. There’s a common perception, though, that academic centers have greater credibility than private sites. Whether or not that’s true is anyone’s guess.

There are purists who believe that unless a site is tied into an established academic group—in other words, a non-profit setting—the data does not carry weight. Purists might argue that results presented at ASCO, for example, might be dismissible because the study wasn’t done at a Harvard or an MD Anderson-caliber center. This is an important issue for some sponsors and a non-issue for others.

Private sites

In some parts of our industry, private sites suffer from a perceptual lack of credibility. However, a growing number of private sites have created the dedicated team and infrastructure to efficiently and effectively collect high-quality data for your study. These sites are typically headed up by physicians who have implemented an academic-type structure in a private setting.

One example is Premiere Oncology of California and Arizona. Dr. Lee Rosen and Dr. Michael Gordon created Premiere Oncology by combining rigorous academic-like processes with a more entrepreneurial pace. (Note: Dr. Gordon is one of the medical founders of Medelis, and we often recommend Premiere Oncology to sponsors.)

Other private sites might not have a fully dedicated phase I team but could have a dedicated research nurse or study coordinator instead of a complete team. Still other private sites have a single staff that handle all trials (phases I through III), which can create challenges if the entire team didn’t cut their teeth on phase I trials.

Advantages of private sites

If you’re able to find the right private site, you’ll probably find that they can ramp up faster (typically 6 to 8 weeks) compared with 4 to 6 months for academic sites. The bureaucracy from the many institutional levels at academic sites are the main reason for this lengthy timeframe.  (Note:  We have had great experience and rapid, efficient start-ups at Scottsdale HealthCare's Virginia G Piper Cancer Center, where the experienced staffs from TGen Clinical Research Centers and the Scottsdale Clinical Research Institute collaborate on over 20 cancer studies.)

The other benefit you’ll find from most private sites is that they’re often less expensive. Academic centers add what they call their indirect, or overhead, rate and it adds anywhere from 25% to 35% to costs.

Balance your needs

The decision regarding what kind of site to use should balance the need for rapid start-up with the need for high quality, accurate data. A high-quality academic center can raise the profile of your trial, but are you able to wait six months for the first stream of data?

If your main concern is getting clinical data as fast as possible because of budget concerns, private sites are probably your best bet. If budget and time aren’t much of an issue and you have a potential blockbuster, academic sites will suffice. Most sponsors we talk to fall into both categories – they want high quality data fast, are focused on driving down clinical trials costs, and desire the top investigators.

For them, we recommend using one of each. Use the private site to get the study launched, enrolling patients in the first 8 weeks to gain quality data at an affordable price. Then enroll the later patients at the academic center to add the credibility (whether it’s real or not) that satisfies the academic world and the investors looking for names like Johns Hopkins, MD Anderson, Vanderbilt etc. for your trial.