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Implementing a "just-in-time" site activation process effectively can significantly speed trial startup.
Clinical trials have never been a more important part of the drug development cycle. The demand for high-quality, dependable, and consistent trials has never been higher as pharmaceutical companies feel more and more competitive pressure to discover and test a wide array of drugs in locations all around the globe.
At the same time, CROs are under their own pressure to reduce costs and remain competitive with other CROs while maintaining a high level of quality for their sponsor clients.
It's a challenge that also presents a tremendous opportunity for those CROs willing to identify and execute new ways to streamline key site activation processes, leverage new tools to pre-certify a number of steps in investigator site recruitment and set-up, and avoid wasteful repetitive steps that add time and cost to trials.
Implementing a “just-in-time” site activation process effectively can significantly speed trial startup. In this model, sites are engaged in the site activation process before there is an approved protocol. Master Clinical Trial Agreements (CTAs) are executed, certain budgetary items are pre-negotiated, and non-protocol specific essential site documents (i.e. CVs, medial licenses) are collected.
Sites that are selected to participate in this kind of activation process are typically ones used by a sponsor on a routine basis. This approach to site activation essentially has the site primed and ready to be fully activated as soon as a protocol is approved. Tufts estimates it takes an average of 45 days to execute a CTA at a central IRB site and an average of 145 days to execute a CTA at a local IRB site. That is a long time, and time is money. This drawn out process delays delivery of life-saving products to market and slows the all-critical return on investment for pharmaceutical companies. From a business standpoint, it can also serve to discourage pharmaceutical companies from developing drugs because the costs are so high.
But CROs can seize a competitive advantage. Early evidence suggests a robust just-in-time activation program can slice those activation times cited by Tufts in half or even more. That translates into going from 45 days to execute a CTA at a central IRB site to 14 days, or going from 142 days to execute a local IRB site CTA down to 30.
There are an estimated 5,400 drugs in development worldwide today. Clinical trials are being conducted in more and more locations, each demanding an understanding of local laws, customs, and nuances that can make or break a trial. But, as the Pharmaceutical Association of America (PhRMA) has recently reported, less than .01% of drugs ever make it to the marketplace. On average, it takes 10-to-15 years and $1.2 billion to develop a drug. Clearly, the pressures are great to find the most efficient ways to vet drugs in the quickest, most economical way.
As someone with years of experience with big pharma, I've heard repeatedly from professionals at investigator sites, industry conferences, and in other conversations that they are increasingly frustrated by what they view as having to reinvent the wheel over and over again with some sponsors and CROs.
Just-in-time activation can isolate some of the most time consuming and unnecessary bottlenecks by enhancing the site selection process and addressing some critical start-up tasks earlier in the process.
Pre-negotiated contract terms is just one area where there are a number of ways to save time. For example if a site has a known $1k pharmacy fee, that fee can be built into a master CTA. That avoids a time consuming back-and-forth exchange of the same information as agreements are negotiated. Similarly, many sites have a non-refundable startup fee. These kinds of fees and certain standard contractual language are items that can be plugged into a master agreement at the outset and re-used on multiple clinical trials. By employing this kind of process standard contractual and budget terms can be negotiated in advance of a clinical trial, allowing negotiators to focus on the protocol specific items when a trial is in the activation phase.
As we all know, effective site selection is one of the foundations for any successful clinical trial. Again, there are many pieces of data that can be teased out and applied to an agreement from the outset without wasting hours or days with the same questions and answers going back and forth between CRO and site. As an example in Latin America, where CROs must work with a national health network, the physicians are often government employees. That changes the payment structure. It also raises questions of currency, e.g. are US dollars acceptable or does the CRO need to work with local currency? These factors are well-known in advance and can be built into an overarching master CTA.
Looking more closely at the physician frustration issue, there are also opportunities to save time and money. Sponsor companies tend to work with many of the same physicians across their portfolio of studies. This means there is an opportunity to collect certain essential site documents required at activation (i.e. CVs and medical licenses) from potentially participating physicians. In addition, site demographic data collected for one trial can be used to pre-populate essential site documents in other trials in which the site participates. With the right technology platform and sound operational process, sponsors and CROs can eliminate redundant data and document collection activities, and can often use the same data and documents for multiple studies.
The reality today is that a CRO might work with the same physician half a dozen times each year, yet they still often collect the demographic information and non-protocol specific essential documents each time. This effort can be handled much more effectively at the enterprise level.
There are other automated ways to save time and money. For example, the basic generation of contractual documents is often done manually, with data being hand keyed, and revisions sent back and forth, sometimes via snail mail. Too often, this translates into entry errors and wasted effort filling out some of the same information each time. Instead of using email and manual population of Excel spread sheets to track data, deadlines, and revisions, there are new technologies available to automate those processes.
In fact, there are robust tools available to pre-populate reams of documents as well as the ability to target approval and sign sections to significantly streamline the process. The time savings can be immense.
"There is simply too much time and paper being wasted today as CROs toil to activate sites and work with pharmaceutical companies," notes Ibraheem Mahmood, President and CEO of DrugDev. "The savings are there for any CRO with the right tools and technology. The benefits of a just-in-time activation program can be across their study portfolio, from small Phase I studies to large Phase III programs. But the larger the study the greater the ROI, with significant returns occurring on studies with 50 sites or more."
There are some hurdles still to overcome. For starters, pharmaceutical companies tend to be technology-averse. Big pharma has been slow, for example, to embrace the wide usage of embedded e-signatures. "Understandably, this is a sensitive area for pharmaceutical companies,” Ibraheem Mahmood says. “They must be very careful with patient privacy, but today's esignature technology is strong, and just changing this one process can shave 15-30 days off the site activation time for a clinical trial."
It's a competitive marketplace, and all signs suggest it will continue to be more and more challenging to thrive. Whether facing new government regulations, new demands from pharmaceutical companies, or other competitive pressures, a CRO would be well-advised to assess and strongly consider the benefits of just-in-time activation. The tools are available. The time savings have been proven. The opportunity is here.
About the Author
Jim DiCesare helps foster strong relationships between sponsors and investigative sites by leading the clinical trial start-up process, which includes the collection, review, and tracking of essential investigator site documents as well as the negotiation of clinical trial agreements (CTAs). He can be reached at firstname.lastname@example.org