10 Steps to Clinical Study Start Up: Step 6 – The Clinical Trial Agreement (CTA)

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10 Steps to Clinical Study Start Up: Step 6 – The Clinical Trial Agreement (CTA)

This is the sixth installment of our ongoing series on 10 Steps to Clinical Study Start Up. We hope you enjoy it. And of course feedback/comments/thoughts are welcome!

The Clinical Trial Agreement (CTA):

This document which can go by other names, like any other document processed in the clinical trial start-up process, is mandatory and often proves to be responsible for substantial delays in site activation measured in days, weeks, or months.

The CTA is a legal binding agreement between the sponsor and the institution; whereas the sponsor typically provides the study drug or device, financial support, and proprietary information; and the institution provides data and results, publication or input into publication, and potential further intellectual property. The CTA achieves important functions between sponsor and site such as: allocation of: risk, responsibilities, obligations, and financial commitments. It also serves to protect both parties with regard to academic, legal, and intellectual property rights.

Typical sections of the CTA are:
* Preamble
* Acknowledgements & Responsibilities
* Term & Termination
* Payment/Reimbursement of Costs
* HIPAA, Patient Privacy
* Publication
* Intellectual Property
* Confidentiality/
* Proprietary Information
* Indemnification
* Insurance
* Subject Injury
* Waiver of Consequential Damages
* Miscellaneous
o Export Controls
o Governing Law
o Dispute Resolution/ Arbitration/Mediation
* Exhibits (e.g. budget & payment terms)

Executing the CTA

The CTA will almost always include the sponsor and institution/site, and may also include a CRO as a third party; in which case the document will outline the same parameters for CRO involvement. Since ultimate responsibility at the institution rests on the principal investigator, it is almost always the case that the PI must sign the CTA.

Sponsors have template CTAs that they use with every site, though they may have different templates for different kinds of institutions with which they may work (independent research site, academic institution, site network, etc). The contracting process begins when the site receives the template contract from the sponsor. Following institutional review of the CTA template, one of two things may happen. They may either sign and return it to the sponsor for full execution, or they may redline their requested changes and return the edited version to the sponsor for approval.

Hurdles

As one can surmise by looking at the contents of a CTA, there are many potential points of contention outlined within this document, with indemnification, insurance, intellectual property, and budget being some of the hot spots. Again, each topic within the CTA merits its own study and the purpose of this blog will be to look at the bigger picture of road blocks and remedies in the CTA execution process.

Both parties (or all three if a CRO is also included) may present limiting factors in efficiently executing the CTA.

Beginning from when the CTA is first generated, most sites will want to see the budget and CTA prior to completing the regulatory package for the IRB. It is reasonable for the institution/site to want to confirm that the study will be equitable for them. Typically, sites are not compensated throughout the start-up process, so completion of regulatory work before they are certain they will be working on the study (i.e. they can afford to), would be a marked misuse of resources. Oftentimes; however, due to internal sponsor or CRO SOPs, the budget, CTA and regulatory pack are all delivered simultaneously. It is not uncommon for the CTA and budget to follow the regulatory pack weeks later.

Poor delivery of the CTA can include ill-thought out timing as discussed above, but the delivery method can also impede efficient CTA processing. The sponsor that sends the regulatory pack with 3 hard copies of executable CTAs when first delivering the CTA is making a big presumption – that is that the site will approve the language within the CTA as is, sign, and return all three copies. While it is still common place for sites to accept the initial language in the CTA as well as the budget offered, it’s baffling why so many variables within these documents are negotiable and site or state or country specific.

It would behoove all parties if the CTA was delivered in an editable, electronic format from the person with whom negotiations will eventually take place. Ideally, this would be done immediately after the site has been approved for initiation. Truthfully, it does not hurt to send them even earlier in the start-up process. It is not uncommon for sites to forgo initiation due to an inability to come to mutually acceptable terms in the budget or CTA. If delivery is done prior to the pre-study visit, and the site does not agree to the terms, at least the early identification of this eventuality will minimize the loss of dollars and time spent by the sponsor &/or CRO in the start-up process. Furthermore; recognizing the site’s need to negotiate these documents and facilitating that process for them will assure that sponsor and CRO teams have done what they can to minimize delays due to contracting.

Tips:
* The site will be at a disadvantage if they have not spent adequate time and resources in developing their own internal CTA/budget SOPs and trainings.
* Knowing well what the guidelines and restrictions are for your state and site will service sites well when red-lining the sponsor’s template
* Basic negotiation skills are essential for the sites to facilitate an efficient completion of the CTA
* A phone call, in tandem to the email with the edited CTA is a nice touch and helps pave the way for successful negotiations
* Basic preparation such as having an up-to-date insurance policy to share should the sponsor require verification
* 48-72 hours is a reasonable expectation in turnaround time for the first red-line draft to be delivered

Allan Valmonte is a Senior Director of Business Development at goBalto and has over 12 years of biopharmaceutical drug development experience. He served as a clinical research consultant for KAI Pharmaceuticals and StemCells, Inc., and held positions in clinical research and development at OXiGENE, Cerexa, and Telik. He has also worked on early, late, and post-approval programs for Integrilin® (Millennium), Vectibix® (Amgen), Lipitor® (Pfizer), and Xolair® (Genentech). Allan holds a B.A. in psychology from California State University, Hayward.

Erik Sam is the Senior Director of Customer Development at goBalto and began his career as an engineer in the Process Research and Development department at Genentech, Inc. There he developed and optimized manufacturing processes in Late Stage Purification for numerous products entering clinical trials. He also ran successful GMP campaigns and collaborations with outside vendors to develop new technologies for the entire biotech industry. Erik holds a B.S. in chemical engineering, with a focus in biotechnology, from the University of California, Berkeley.

Dan Manak is a Senior Director of Business Development at goBalto and a graduate of the University of Wisconsin – Madison. After earning his bachelor of science degree in Molecular Biology he began his career in pharmaceuticals with Hoffman-La Roche, holding positions in sales, sales management, and training. He has worked in pharmaceuticals, health care, and clinical research for over 20 years with Fortune 100 companies as well as start-ups. For the past seven years he led a small clinical research service organization as the President and Director of Business Development. His expertise and passion exist specifically in the area of clinical study start-up, having worked on several hundred protocols and initiating close to a thousand investigative research sites. In his spare time, Dan is a volunteer EMT and martial artist/Instructor.

About goBalto: goBalto is a small team that creates simple, focused and affordable web based software for the global clinical trial industry. Our products offer drug trial sponsors the easiest possible way to start their clinical studies on the web, which makes them feel better. www.gobalto.com