How To Cut Clinical Time And Cost With CRO Continuity

By Ed Miseta, Chief Editor, Clinical Leader

Roxanne Tavakkol, VP of Regulatory and Scientific services, TKL Research

Roxanne Tavakkol has a lengthy track record in the pharmaceutical industry. Currently the VP of Regulatory and Scientific services at clinical firm TKL Research, she began her career on the sponsor side of the house and has been involved in over 10 NDA registrations in her 20-year career in pharma. This experience has instilled in her the importance of solid data and streamlined data collection process in clinical trials.  

“When FDA reviews an application for a registration, the primary concern to them is the risk/benefit to the patients,” she says. “That is not news to the pharmaceutical industry. We all know the quality of the data will ultimately determine whether or not a drug is approved. But I do think a lot more attention is now being paid to how the choice of a CRO can affect that the quality of the data.”

Although data is submitted to FDA by pharma sponsors, many companies are now using CROs to perform clinical trials. When a trial is outsourced, it is the CRO that has all of the interactions with the clinical sites, investigators and ultimately the patients. Pharma is increasingly looking to CROs for protocol development, patient interaction, and data collection, analysis, and delivery. Unfortunately, that also means the sponsors are getting more distant from the front lines of the study.

“As pharma becomes more distant from the patients, it becomes more vital for them to do business with CROs that can produce quality data via close connections with the clinical sites,” says Tavakkol. “In my career, there have been occasions where the data collected during the study was so messy that reaching a firm conclusion was a challenge. When there is a lack of proper planning and understanding of the patient interactions with the clinical team at the site, the result will generally be poor data that is difficult to interpret. Sometimes the protocol is not clear, or site personnel simply did not fully understand it. This is more likely to happen when the individuals designing the protocol are far removed from the people actually working with the patient.”

Continuity Leads To Better Results

The CRO ensures the that the sites have an intimate understanding of the study protocol, the right patients are involved in the study, the patients stay committed to the study, and that the knowledge learned in earlier studies can be used and built upon in later studies. Therefore, CRO continuity can have a very positive impact in the process.

If the data from a Phase I study is promising, the sponsor will advance the molecule to Phase II and Phase III, which involve larger patient populations. This is where the transition of the knowledge learned in earlier phases will determine how quickly and efficiently the study is done. When changing CROs from one phase to the next, some of the valuable information learned in earlier phases may not be passed along.

A CRO performing a study will receive feedback from the patients, learn how they react to the drug, and understand the difficulty in collecting the data. Losing some of that first-hand knowledge when advancing from one phase to the next can result in slower recruitment, a higher number of dropouts, or the data not being collected cleanly. This will often result in delays and an increase in the number of patients required for enrollment.

“The primary concerns for pharma is patient safety, controlling cost, and getting the product to market as quickly as possible,” notes Tavakkol. “The best way to control all three is to know your target patient population. Continuity in your CRO will give you a huge advantage in that regard. A CRO that performed an earlier study will already have a database of patient information and will understand the patient population they are going after.”

Bringing a CRO onboard as early as possible and maintaining that CRO throughout the different phases is a key contributor to having a successful clinical development program. At the very least, the same CRO should be carried over from Phase II to Phase III, as long as the sponsor is pleased with the performance. Although the sponsor maintains regulatory responsibility for the program and performs site visits and audits, it is not there on a daily basis dealing with the site, gathering the data, or talking to patients.

Patient Recruitment Made Easier

One of the primary advantages of CRO continuity that cannot be overlooked is patient recruitment, which seems to be getting more difficult, time consuming, and costly. “The first time you do a study you screen a lot of patients and will have some amount of screen failure,” says Tavakkol. “The CRO staff conducting the screening will know why certain patients did not get enrolled. They will know who was screened, the primary cause of screen failure, and the signals that made it likely a patient would be enrolled. They will also know, for future studies, how to come up with a better screening pool. That screen failure information does not always make it into a clinical study report. Usually, the only data presented there is as a number. A new site that does not have access to the source information will have to start from scratch, which will waste a lot of time.”

Some CROs offer specialized recruitment management programs, which is a powerful tool for increasing enrollment speed and meeting tight timelines. In many cases, the individuals on the project teams at the CRO and the sites are maintained from Phase II to Phase III, creating additional momentum in the recruiting process.

A successful product registration will always come down to the efficacy and safety of the drug. Tavakkol has seen the worldwide regulatory environment get more conservative over the course of her career. She believes the greater emphasis on safety has led to many effective drugs not gaining approval. When sponsors stay with the same CRO over the course of Phase II and Phase III, this creates the opportunity for both the sponsor and CRO to have an integrated perspective on what the safety profile of the product looks like, which she believes will benefit the sponsor when preparing the registration packet.

“Clinical research is also about generating a side-effect profile,” she says. “Having that understanding of the common side-effects of the drug being studied is critical to gaining approval. The continuity in a CRO helps to understand the effects better, and that continuity comes down to knowing and interacting with the patients. I believe the continuity will help sponsors explain that side-effect profile more clearly to the Health Authorities.” 

Selecting The Right CRO

According to Tavakkol, there are several factors to consider when selecting your CRO. The first is the ability to build on early studies and transfer knowledge from one phase to another. To evaluate this ability, ask the CRO about their experience transitioning products between phases of development.  Also ask how it transitioned knowledge from one project team to another. She believes CROs should always have a discussion of lessons learned at the end of every trial, which would include a plan detailing how to move forward into the next phase.  

The CRO should also have an experienced regulatory group that has worked with both large and small pharma companies. “While large pharma companies already have regulatory experience, many of the smaller biotech companies will need their CRO to have a broad regulatory background.” says Tavakkol. “Asking how many Phase ll studies they have worked on and how many study approvals they have gained will also give you an indication of their level of expertise.”

Finally, Tavakkol advises caution when working with “one size fits all” CROs. A large CRO performing both an early phase and late phase study may have entirely different teams performing the studies, which would negate the continuity advantages of dealing with the same team. “The end result is the same as if you had changed CROs,” she adds. “The new team will not have access to some of the lessons learned because they were not involved in the earlier studies. When dealing with one of these firms, be sure to ask who will be working on the study and whether there will be continuity of the staff. In summary, pharma sponsors should look for a CRO that cares as much about the success of the study as they do, has close relationships with the study sites, and has experienced data management and regulatory staff.”