By Débora S. Araujo
By Débora S. Araujo, Boehringer Ingelheim
Imagine for a moment you are your favorite superhero, charged with the task of saving the whole world from villains such as the Joker, Lex Luthor, Doctor Doom, and the Green Goblin. You would not be very effective — or much of a superhero, for that matter — if you only took one of them out while letting the others roam free. In the same way, as an industry, we cannot effectively tackle the issue of delays in the execution of Clinical Trial Agreements (CTAs) by only addressing one or two of the “villains” contributing to this industrywide problem.
Currently, executing a clinical trial agreement (CTA) between sponsor/CROs and sites takes a median of more than three months globally and more than two months in North America.1 The delays have a real-life impact on thousands of patients who desperately depend on the execution of such agreements to be able to participate in a potentially life-saving clinical trial at their local investigator site.
It is widely known that legal language is one of the main villains threatening the timely execution of CTAs. The issue has prompted much-needed industry focus and related initiatives in recent years, in an effort to standardize legal language and thus streamline negotiations. However, to effectively address the overall delays in CTA execution, the other “villains” causing this delay must be dealt with alongside the legal language piece. The following are some of the top villains threatening an expeditious study start-up and some ways to counter each of them.
Villain #1 – Limited Negotiation Parameters
Sponsors usually have either internal staff negotiating CTAs or have a CRO/vendor handling this task. For mid-size and large sponsors, the contract negotiators handling this task usually do not reside within the legal department and are not necessarily attorneys. Negotiation parameters or a CTA playbook is usually developed by the sponsor’s legal team and provided to the contract negotiators to aid in the negotiations. Such playbooks are vital to expediting the negotiation process and reducing the need for escalation in approving routinely requested modifications that the sponsor would agree to under certain circumstances. It is important for sponsors to update their playbooks periodically to reflect routinely requested items or new industry trends for both language and budget. Failing to maintain the document and/or keep the parameters current and comprehensive defeats the document’s purpose. This process may be time-consuming up-front and requires periodic review, but it will streamline and speed up negotiations significantly.
Villain #2 – Site Budget Negotiations
If you are involved in study start-up, you have likely seen many instances where the sponsor/CRO and site have agreed on the legal language of the CTA only to have things still delayed due to the site budget. Possible solutions to this problem include:
- Tailor budgets while maintaining fair market value. Many sponsors and CROs across the board develop one standard site budget for a country (some keep the same for all countries) and send this out without ever taking into consideration geographical locations, institution size, or other pertinent information. This increases the number of days sites will need to revise the budget proposal with more appropriate numbers — and the number of days required to obtain the necessary internal sponsor approvals to revise the budget items.
By starting out with a robust, accurate, and fair site budget based on geographical location, institution size, site intelligence, etc., we can shrink the number of days needed for the back and forth between sponsor, CRO/vendor, and site. Sponsors should take into consideration differences in healthcare costs between different geographical locations, even within a country.
Objections to this approach are usually rooted in the fear of not maintaining fair market value (FMV). To clarify, maintaining FMV while producing more accurate and robust site budgets can be achieved if the sponsor/CRO has a standard process they apply consistently across the board and can show proper documentation to prove they have followed this process in the event of an audit.2
The key here is setting up an excellent initial structure to assure a consistent process that is replicated for all sites while considering their unique differences – this is the key to maintaining FMV. This solution may require some time up front to build the infrastructure, but it will also prove to be amazingly effective in speeding up site budget negotiations.
- Negotiate master site budgets. For those sites with which the sponsor has already negotiated master agreements, it may be beneficial to establish a master site budget as well. By coming to an agreement on certain routine costs and fees, the return on investment of that negotiation time will be invaluable in expediting future trials with that site.
- Start with previously approved fees. If a master site budget is not a possibility, simply customizing the site budget prior to sending out to a recently used site may slash negotiation time. Items such as overhead, fixed fees, and other appropriate costs are many times not protocol specific and can help start negotiations on a good note as well as reduce the back and forth. There is no reason to begin a site budget negotiation without using recent site budget business intelligence as the starting point.
Villain #3 – Lack Of Understanding Of Country/Site Requirements
Take the time to understand if the countries and sites on your list have specific requirements such as specific model agreements regularly used, unique regulatory requirements and timelines affecting the CTA execution, any special approval requirements other than regulatory bodies, which parties need to be involved in negotiations, or any other unique situations. Many of the issues that result in delays in CTA execution can be solved by proactively seeking business intelligence and an understanding of the specific sites being used for a study and appropriately planning/preparing for them. This approach is important whether a sponsor is conducting a study in their home country or in multiple countries.
Villain #4 – Cumbersome Internal Processes
Ever heard the idiom “the devil is in the details”? This is a good description of how significant delays can be hidden in something as plain as internal sponsor/CRO processes for CTA negotiations and execution. Sponsors should review their internal processes for approvals during negotiations — whether they are negotiating using internal staff or a CRO/contract negotiation vendor — and look at opportunities to delegate authority to appropriate individuals to expedite the negotiation process. Only individuals who add true value to the process or have approval authority in the matter should be involved. Otherwise, streamline, streamline, streamline.
The Unintended Consequences Of CTA Delays
The impact of delays in CTA execution has gained new meaning in the clinical trial community through the story of T.J. Sharpe, who was diagnosed with Stage IV melanoma at age 37 and found a glimpse of hope in a clinical trial — only to have that hope threatened by a six-week delay in joining the trial due to a CTA not being executed.3 T.J’s story, and countless other examples throughout the years, have prompted industrywide initiatives attempting to solve the issue, mainly from the language aspect of CTA negotiations. Although legal language is an extremely important piece of CTA negotiations, and should be streamlined and standardized, it is only one of the components affecting the execution of the CTA. By addressing this industry issue via a strategic and holistic view, sponsors/CROs can decrease delays in CTA execution, speed up study start-up by weeks, and let patients like T.J. know that we have not only heard them, but that we are listening.
- KMR Group. Site Contracts from Weeks to Months: Results from KMR Group’s Site Contracts Study. Biospace.com. 24 August 2016. Accessed from: http://www.biospace.com/News/site-contracts-from-weeks-to-months-results-from/430240
- “How to Negotiate Study Budgets,” Norman M. Goldfarb, Journal of Clinical Research Best Practices, Vol. 12 No. 8, August 2016.
- Society for Clinical Research Sites (SCRS), CLEARTM Common Language Evaluation and Reconciliation (White Paper), October 2016.
About The Author:
Débora S. Araujo has over 10 years of experience within clinical trial operations with a special focus in the areas of global clinical contracting and clinical financial management. Her previous roles include both large and small pharmaceutical sponsors, as well as the investigative site side of clinical trials. Working within organizations such as Novartis Pharmaceuticals, Eisai, Inc., and Merck & Co., among others, has given Débora unique insight into the systemic blind spots sponsors have regarding clinical contracting and clinical financial management, particularly investigator site payments. In her current role as associate director of clinical contracting services within Boehringer Ingelheim, Débora manages, from both a strategic and tactical level, driving global harmonized processes for clinical contracting and clinical financial management with a strong customer focus.
The views expressed in this article are not necessarily those of Boehringer Ingelheim Pharmaceuticals, Inc.
Image credit: J.J. at the English language Wikipedia, CC BY-SA 3.0, Link