Building Quality into Clinical Trials with Effective Protocol Design Comprehensive Roadmap to Study Protocol Quality by Design June 11, 2013 By Kenneth Schif
President, Quality Risk Management Associates, LLC
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Table of Contents Introduction Current Overview Utilizing Quality Risk Management Significant Benefits Conclusion Amendment Q&A
7303 Introduction The pharmaceutical industry has been developing clinical trials utilizing the same protocol designs for over 20 years, yet studies continue to indicate the same bad news when it comes to regulatory inspection findings: that despite extensive quality risk management procedures, over 60 percent of clinical trials have at least one amendment, and 43 percent of amendments were signed off by sponsors before the first patient was even enrolled. What may be worse is that 13 percent of any given project’s amendments are somewhat avoidable…and up to 20 percent are completely avoidable! INSERT SLIDE #21 And that’s expensive. The cost of performing just one amendment: approximately $450,000. What is this telling us? Obviously that we're not building the kind of protocol designs that will gather the information we really need beforehand. That we have to think better, think smarter, when we're putting trial protocols together. That’s why so-called quality by design is a very hot topic in the industry at the moment, resonating with healthcare professionals, the pharma industry, the biotech industry, as well as the service providers and contract research organizations. It’s not a new concept. It’s been utilized among many industries for many years, for example within the manufacturing, where it works very nicely. Now we want to understand how to build quality by design into a specific aspect of our clinical work: our clinical trial protocols. We can use it from the very beginning (and the sooner the better) in protocol synopses, and ultimately to the actual protocol design.
This presentation looks at rethinking the utilization of quality risk management (QRM) tools specifically in relation to developing more effective protocols, thereby cutting costs, and delivering safer products, from the outset.
Barriers to Effective Quality Design There are a lot of consequences to failing to evaluate current protocol design: INSERT SLIDE # 20 So it would seem there are certainly enough incentives to moving forward. So what are the difficulties? Why are we so many trials generating requests for amendments? There are quite a number of reasons, or there wouldn’t be a need better understand the ways in which quality risk management systems should be utilized, so as to review and modify trial protocols. This report will provide a broad range of issues that need to be addressed, but for now let’s just look at a few key obstacles. 1. Science-only Focus: For decades, only physicians, clinicians, and/or scientists have written trial protocols. That means two things happen: [P. 8] That means these protocols are scientifically driven, rather than reviewed from a complete quality standpoint. And this leads to a very narrow focus; especially since nobody wants to challenge these scientists when we want to make changes to the protocol. In fact, there’s no procedure—such as a review committee—designed to allow for either positive or negative feedback to these experts. 2. Fragmented Data: In most systems our data is fragmented, stored in many different databases. For example: we have safety data, we have clinical trial data, we have trial information in CTMS, we have Oracle Clinical, we have EDC Rave. We have our CROs and our service providers, we have clinical suppliers…and they all have isolated databases. I think one organization told me they had over 100 systems, just to support clinical trials. So, that's quite a lot of systems that are out there, with pretty much none of them coordinating with us, let alone with each other. [p.12] INSERT SLIDE 12