Clinipace Blog

Understanding FDA’s Final Guidance on Exempt Infant Formula Production

Marci Ardinger is the Associate Director of Project Management at Clinipace Worldwide. Infant formulas play an important role in the overall health of infants that consume them, and the FDA has recognized that infant formulas for specific uses (i.e., infants with inborn errors of metabolism, low birth weight and other medical or dietary issues) might need to differ in their nutrient content from the formulas manufactured and marketed for healthy, term infants. These “exempt infant formulas” are therefore considered exempt from the specific subsections that provided guidance regarding the nutrient content and reporting of the nutrient content of infant formulas in the Federal Food, Drug, and Cosmetic Act (FD&C Act) section 412, which was written specifically to “ensure the safety and nutrition of infant formulas.” Instead, the terms and conditions for exempt infant formulas were provided in the guidance 21 CFR 107.50, “Exempt Infant Formulas.” Last week (April 14, 2016), the FDA issued final guidance for industry on exempt infant formula production. This guidance aims to provide an understanding of the recommended manufacturing standards for exempt infant formulas as they relate to those for non-exempt infant formulas. The manufacturing of these non-exempt infant formulas is guided by 21 CFR 106, which was last amended on June 10, 2014. The FDA recommends that future manufacturing of exempt formulas follow subparts A (general provisions), B (current good manufacturing process), C (quality control procedures), D (conduct of audits) and F (records and reports) of 21 CFR 106, rather than 21 CFR 107.50. Doing so ensures the exempt formulas adhere to sound public health policy that these products should be manufactured using protocols and procedures... read more

Clinipace Statistical Expert Presenting at 5th Annual PhUSE and FDA Collaboration Computational Science Symposium (CSS)

Dirk Spruck, Clinipace’s Manager of Statistical Programming, will share his expertise as part of a working group during the 5th annual Computational Science Symposium (CSS) held by PhUSE and the FDA March 13 – 15, 2016 in Silver Spring, Maryland. Dirk and his collaborators, Hanming Tu of Accenture and Dante Di Tommaso of Roche, will present on behalf of the CS Standard Analyses Working Group. Their poster, titled “The Car is in the Shop, but Where are the Mechanics?”, reviews the future of standard scripts for analysis and reporting. The poster will also be presented at PharmaSUG 2016 in May in Denver, Colorado. Dirk and his co-presenters will review the vision of the CS Standard Analyses Working Group, summarize its progress to date and outline proposals to resource further advances. After meeting its main goal of establishing a framework for standardizing analyses across the industry, the group has made progress along three main areas: The White Paper Project developed guidance on nine data analysis topics and published four papers. The Infrastructure Project established a GitHub code repository. The Content Project established implementation guidelines, established a qualification process and published scripts that display standard measures of central tendency. Moving forward in 2016 and beyond, the group will work to promote adoption of these standard analyses; to coordinate review of, finalize and publish white papers; and to increase the scope, quality and usability of the standard scripts. However, the main challenges to completing the vision of a comprehensive framework for cross-industry standard analysis is the lack of resources. In order to fully realize its vision, the group will work to secure... read more

Clinical Events Adjudication in the Digital Age: A Better Way to Adjudicate

Heather Bristol, MS, is the Vice President of Informatics at Clinipace. Manejeh Yaqub, MD, is the CEC Consulting Expert. Thank you to everyone who attended our webcast “Clinical Events Adjudication in the Digital Age.” In the presentation, we discussed when clinical events committees (CECs) are needed, CEC structures, CEC processes, what to look for when outsourcing CEC services and benefits of technology-enabled CEC processes. During the webcast, we received a number of great questions from the audience. Therefore, we would like to share answers to those questions with you in a series of blog posts. In previous blog posts, we’ve answered questions about therapeutic areas for which standard definitions are unavailable, the CEC structure and the CEC process. In our final blog post, we’ll discuss a major difference between electronic adjudication and traditional adjudication. If you have any additional thoughts or questions for our experts, please share your comments below. Q: Does the FDA or any regulatory agency view electronically blinded adjudicated results more favorably than traditionally adjudicated results? A: There are no clear regulations around this, but from a quality standpoint, in our opinion it is definitely more favorable. In addition, electronically, one can present blinded adjudications as truly independent assessments. Finally, electronically blinded adjudication provides good audit trails, which, in our opinion, are viewed more favorably by regulatory authorities.   If you’re interested in learning more about clinical events adjudication in the digital age, be sure to download our recorded webcast and the associated... read more

Clinical Events Adjudication in the Digital Age: The CEC Process

Heather Bristol, MS, is the Vice President of Informatics at Clinipace. Manejeh Yaqub, MD, is the CEC Consulting Expert. Thank you to everyone who attended our webcast “Clinical Events Adjudication in the Digital Age.” In the presentation, we discussed when clinical events committees (CECs) are needed, CEC structures, CEC processes, what to look for when outsourcing CEC services and benefits of technology-enabled CEC processes. During the webcast, we received a number of great questions from the audience. Therefore, we would like to share answers to those questions with you in a series of blog posts. In previous posts, we discussed how to handle therapeutic areas where standard definitions are unavailable as well as several considerations in relation to CEC structure. Today, we’ll dive into a handful of questions about the CEC process. Check back Thursday for our final blog post of this series, in which we’ll discuss the difference between electronic adjudication and traditional adjudication. If you have any additional thoughts or questions for our experts, please share your comments below. Q: Are all members of the CEC unblinded to study treatment? A: It depends on the study. If the study protocol calls for blinded treatment for patients and the sponsor is blinded, the CEC will also likely remain blinded. However, if it’s an open-label study, there is no way to blind members of the CEC because they are actually reviewing the chart from the source level. There may be other study designs where it’s not possible to blind CEC members, so it really follows the protocol blinding criteria. Q: Can efficacy data be part of a CEC? A: Yes,... read more

Clinical Events Adjudication in the Digital Age: CEC Structure

Heather Bristol, MS, is the Vice President of Informatics at Clinipace. Manejeh Yaqub, MD, is the CEC Consulting Expert. Thank you to everyone who attended our webcast “Clinical Events Adjudication in the Digital Age.” In the presentation, we discussed when clinical events committees (CECs) are needed, CEC structures, CEC processes, what to look for when outsourcing CEC services and benefits of technology-enabled CEC processes. During the webcast, we received a number of great questions from the audience. Therefore, we would like to share answers to those questions with you in a series of blog posts. Last week we discussed how to handle therapeutic areas where standard definitions are not available. In this blog post, we’ll answer a few questions regarding CEC structure, including the ideal committee size, if committee members can change during the course of a study and more. Check back next week for answers to more questions about the CEC process. If you have any additional thoughts or questions for our experts, please share your comments below. Q: What do you see as the ideal committee size, and how do you decide how many members to include? A: It depends on the study. It is preferable to have a committee of odd numbers, and three-member committees are popular. In a large-volume studies with aggressive study milestone timelines or commitment challenges, five-, seven- or nine-member committees can be set up with a quorum decided upfront. The ideal committee size also depends on the therapeutic area of the study. For example, a study with events randomized to CABG, PCI and medical therapy may need a CV surgeon, an interventional cardiologist... read more

Clinical Events Adjudication in the Digital Age: Therapeutic Areas Without Standard Definitions

Heather Bristol, MS, is the Vice President of Informatics at Clinipace. Manejeh Yaqub, MD, is the CEC Consulting Expert. Thank you to everyone who attended our webcast “Clinical Events Adjudication in the Digital Age.” In the presentation, we discussed when clinical events committees (CECs) are needed, CEC structures, CEC processes, what to look for when outsourcing CEC services and benefits of technology-enabled CEC processes. During the webcast, we received a number of great questions from the audience. Therefore, we would like to share with you answers to those questions in a series of blog posts. In today’s post, we’ll discuss how to handle therapeutic areas where standard definitions are unavailable. Check back Thursday for more questions regarding CEC structure. If you have any additional thoughts or questions for our experts, please share your comments below. Q: Standard definitions are available in some therapeutic areas like cardiovascular and cerebrovascular, but how do you handle areas where standard definitions are not available? A: It depends on the protocol. You’re right that standard definitions are more widely available in the cardiovascular and neurovascular therapeutic areas. However, there are protocols with specific endpoints that may require higher utilization of consistent definitions, which the CEC can also help refine for future scientific endeavors. Therefore, it really depends upon what endpoints or safety events each study is looking for. A good example would be stem cell studies that involve harvesting of stem cells through sternal puncture, which are prone to bleeding complications that are often severe and serious. For such studies, a consistent bleeding definition distinguishing various categories of bleeding would be of potential benefit. CEC... read more

Making Sense of Rising Oncology Drug Costs

Mark Shapiro is the Vice President of Clinical Development at Clinipace. Although cost control for drugs has been common in countries with socialized medicine or government-payer systems, this issue is now beginning to take center stage here in the United States.  Despite wide coverage in the popular media, such as Dr. Ezekiel Emanuel’s editorial in The New York Times, it was quite striking to see calls for more value-based pricing at the American Society of Clinical Oncology (ASCO) meeting earlier this year. The cost of new drug development is the most-often-cited justification for the high and rising cost of new drugs.  According to the team at the Tufts Center for the Study of Drug Development (CSDD), “developing a new prescription medicine that gains marketing approval, a process often lasting longer than a decade, is estimated to cost $2,558 million.”  That figure includes average out-of-pocket costs of $1,395 million and time costs (expected returns that investors forego while a drug is in development) of $1,163 million.  Relative to their study in 2003, the CSDD estimates that “the cost to develop and win marketing approval for a new drug has increased by 145% between the two study periods, or at a compound annual growth rate of 8.5%.” Despite these dramatic costs, it has long been known that pharmaceutical companies price drugs based on value and demand rather than cost, to the extent possible. Of course, this is also subject to formulary negotiations with insurers. Strong biotechnology investment in new oncology therapeutics has partly been justified by the relative price insensitivity of oncology drugs versus other types of therapeutics.  This has led... read more

Clinipace Worldwide Honored in Inc. 500|5000 List for the Sixth Year Running

We’re having a great morning because we’ve been named to Inc. Magazine’s 34th annual Inc. 500|5000 list – for the sixth year running! The Inc. 500|5000 list represents the most comprehensive look at America’s independent entrepreneurs. Started in 1982, this prestigious list of the nation’s most successful private companies has become the hallmark of entrepreneurial success. Clinipace by the numbers: 321% revenue growth from 2011 to 2014 466 jobs added during that period Facts and figures of the 2015 Inc. 5000 Health is the 8th fastest growing industry by aggregate growth rate (147%) North Carolina is the 11th fastest growing state by number of companies (145) “Being recognized by Inc. on a global business level for the sixth year running provides validation for our work. We’re in a very competitive marketplace and we strive to continuously innovate, expand our therapeutic expertise and improve our service delivery model to stay ahead of the curve.” – Jeff Williams, CEO, Clinipace Worldwide This recognition follows our announcement earlier this year of our acquisition of Accovion, a leading European full-service CRO headquartered in Frankfurt, Germany. The move strengthened our operational and therapeutic expertise within Europe and marked our sixth acquisition in as many years. We now have nearly 1,000 global staff members with clinical operations and staff in 39 countries, including North and South America, Europe and Asia. For more information on Inc. and the Inc. 5000 Conference, visit... read more

New eBook: Streamlining the Regulatory Path to Market for Low-Risk Medical Devices

U.S.-based companies dominate the roughly $350 billion global medical device industry, and, as a result, the United States exports more medical devices than it imports. The U.S. Food and Drug Administration (FDA) is responsible for regulating firms that manufacture, repackage, relabel, or import medical devices sold in the United States. It categorizes medical devices into three classes based on the level of regulatory control needed to provide reasonable assurance of safety and effectiveness. Because Class III devices pose a potential for serious risk to humans, all Class III devices must be evaluated in clinical trials before receiving Premarket Approval from the FDA. The clearance process for Class I and II devices is often simpler and commonly does not require novel clinical trial data. Class I and II devices rely mostly on safety and performance data in accordance with quality regulations and consensus standards. Especially when clinical trials are not required, developing Class I and II devices is very feasible for small companies without large capital reserves. However, although the process of FDA clearance for Class I and II medical devices is considered easier, the various submission standards are not always obvious or intuitive, and failure to properly navigate them can lead to wasted resources at best and federal prosecution at worst. In this eBook, we review vital steps in receiving FDA clearance of Class I and II medical devices and strategies for streamlining the process. Download our eBook to learn more about: Understanding the classes and corresponding regulatory controls Confirming your device’s classification Identifying predicate devices already cleared for sale Defining your device’s Intended Use Developing a regulatory and... read more

Clinipace’s UK Office Hosts Harding University Students

Martin Cripps is the Senior Director, Project Management, at Clinipace Worldwide. Last week, our UK office hosted a group of Harding University students and faculty as part of their summer program. This is the fourth year in a row we’ve had the pleasure of hosting this wonderful group from the university. Harding University is located in Searcy, Arkansas, and their summer program brings students to the UK to visit various businesses across multiple sectors. The group of business majors was led by James G. Shelton, PhD, professor of accounting at Harding. In addition to faculty sponsors, the group was also joined by Bruce McLarty, president of Harding University; his wife Anne; and Bryan Burks, dean of the Carter College of Business. During their visit, I presented on the state of research and development in health care, including an industry overview, the phases of clinical development, and an introduction to the business and operations of Clinipace. The presentation reflected current industry trends and our growing geographical footprint and services. I’m always intrigued to learn what the students are most interested in. In previous years, topics of interest have included the phases of clinical development, pricing, and intellectual property. This year, students asked many questions about our TEMPO eClinical platform functionality and our global project operations. They were surprised by the fact that not all companies in our industry have a single data platform. Could this be a sign that technology will be embraced at a faster rate in the future perhaps? As always, I was impressed by the students’ intuitive questions about the pharmaceutical and biotech industry. We would like... read more

Navigating Regulatory Biostatistical Requirements During Trial Analysis and Submission: Post Hoc Analyses

Ron Marks, PhD, serves as CSO and director of biostatistics and is a Clinipace Worldwide cofounder. It was a pleasure to host the webinar “Navigating Regulatory Biostatistical Requirements Throughout the Clinical Trial Lifecycle” with my colleague, Scott Miller, PhD, a biostatistician at Clinipace. We reviewed common statistical issues (during trial planning, conduct, analysis, and submission phases) and discussed potential approaches to address these issues. We’ve addressed many excellent questions from attendees regarding the trial planning phase (including protocol deviations, adaptive designs, and alpha spending functions in interim analyses) and the trial conduct phase. In our last posts, we address questions related to trial analysis and submission. If you have any additional thoughts or related questions to ask our experts, please share your comments below. Q: What is the best way to present post hoc analyses to the FDA? A: This is a very interesting question because you can get into really some good discussions about whether or not post hoc analyses are useful. When you write your protocol and especially the SAP, you’re defining all the important planned analyses that are going to take place, which you completely identify before you ever get the database lock and look at your data. That’s clearly what the FDA is going to focus on. But I think you have an opportunity to really use post hoc analyses, especially in Phase II studies more so than in the Phase III studies, to learn more about your product. We have three different stages of analysis: You have the primary analysis, the secondary analysis on your secondary endpoints, and then either exploratory or observational endpoints... read more

Navigating Regulatory Biostatistical Requirements During Trial Planning: Considerations for Adaptive Designs

Scott Miller, PhD, is a biostatistician at Clinipace. Thanks to everyone who tuned in to the webcast “Navigating Regulatory Biostatistical Requirements Throughout the Clinical Trial Lifecycle” I recently hosted with my colleague Ron Marks, PhD, Clinipace CSO, director of biostatistics and cofounder. During the presentation, we reviewed common statistical issues (during trial planning, analysis, and submission phases) and discussed potential approaches to address these issues. As a result of a great turnout and many excellent follow-up questions, we decided to address a number of questions in a series of blog posts. Earlier this week we addressed protocol deviations. Today, we’re going to address considerations for adaptive trial designs. If you have any additional thoughts or related questions to ask our experts, please share your comments below. Q: Can you briefly highlight statistical considerations for adaptive trial designs? Adaptive designs are a fairly broad category that covers a wide range of very diverse topics. Essentially, an adaptive design is a pre-specified process which allows for some aspect(s) of a clinical trial (e.g. design, conduct, analysis) to be changed in light of accumulating data. One example is covariate adaptive design, where you have multiple clinically relevant covariates of interest you need to ensure balance on, but there are too many to account for via stratified randomization. Another example is response-adaptive designs. In a standard trial, you would randomize subjects to the treatment arms based on some fixed randomization ratio (like 1:1 or 2:1) and use that ratio all the way through the trial. In some cases, you might want to adjust that ratio over time either to be more statistically precise,... read more

Navigating Regulatory Biostatistical Requirements During Trial Planning: Understanding Protocol Deviations

Ron Marks, PhD, serves as CSO and director of biostatistics and is a Clinipace Worldwide cofounder. Thanks to everyone who tuned in to the webcast “Navigating Regulatory Biostatistical Requirements Throughout the Clinical Trial Lifecycle” I recently hosted with my colleague Scott Miller, a biostatistician at Clinipace. During the presentation, we reviewed common statistical issues (during trial planning, conduct, analysis, and submission phases) and discussed potential approaches to address these issues. As a result of a great turnout and many excellent follow-up questions, we decided to address a number of questions in a series of blog posts. In our first few posts, we’ll start with questions regarding trial planning. Check back next week for more great questions around regulatory biostatistical requirements during the trial conduct phase. If you have any additional thoughts or related questions to ask our experts, please share your comments below. Q: Will you please list some common protocol deviations? A: As we discussed in the webinar, protocol deviations are defined as events that occur during your study that don’t go according to the protocol. When protocol deviations occur, they get graded during or at the end of the study to determine whether they are major or minor deviations. Major deviations are handled differently than minor deviations, and if you have a major protocol deviation, you are not part of the per-protocol analysis. All clients want to maximize their per-protocol population because that’s the population that followed the protocol. The more major protocol deviations that occur, the more subjects you lose from that analysis. Typical protocol deviations include assessments or visits that occur outside of a protocol... read more

Clinipace Expert Presenting at DIA 2015

Our head of clinical trial regulatory management in Western and Central Europe, Rainer Porrmann, PhD, will share his expertise at DIA 2015 June 17, in Washington, D.C. His presentation, “Current Situation and Potential Future Development of Regulatory Requirements,” takes place in the medical devices/in vitro diagnostics and combination products track and will provide an overview of the current regulatory requirements for clinical trials for medical devices in Europe and key factors of the proposed new European regulations. Unlike the pharmaceutical side of clinical trials, there is currently no separate regulation or directive that defines the requirements and procedures for medical device trials in detail. This can sometimes lead to some insecurity for non-EU sponsors planning or conducting medical device trials in EEA countries. During his presentation, Rainer will discuss the current regulatory framework in Europe for medical device trials, explaining similarities and differences that show the range of potential variability across Europe. In addition, he will highlight key factors of the proposed new European regulations and provide an update about their development to help prepare for the upcoming changes. Attendees will gain an understanding of key implications for sponsors in regards to trial planning, the submission process, timelines, and conducting clinical trials with medical devices in the EEA. DIA is a neutral, global, professional and member-driven association of nearly 18,000 professionals involved in the discovery, development and life-cycle management of pharmaceuticals, biotechnology, medical devices, and related health care products. This annual meeting provides thought leaders, decision makers and patient advocates with the opportunity to collaborate and share knowledge with the top minds in medicine. To learn more about their... read more