The FDA did make sure to provide examples of its proposed enrichment strategies within the draft guidance, a fact that was pointed out by a number of pharmaceutical companies in their official responses and comments. However, some areas – such as oncology – were absent from the document, and some companies also had difficulty discerning whether the FDA was advocating a preferred approach to enrichment design or was merely presenting one of several different possibilities. Furthermore, questions were posed about the statistical details regarding enrichment designs, as well as which types of trials (exploratory versus late-stage) they should be applied to.

The draft guidance in question was reviewed and commented on by Aptiv Solutions staff, and includes a section on the use of adaptive trial design as a potential enrichment strategy. Recognizing that not every pharmaceutical company has the depth of adaptive trial expertise necessary to implement the benefits of this methodology when considering enrichment plans, Aptiv Solutions has put together the ADDPLAN software suite. ADDPLAN features a specific population enrichment module (ADDPLAN 6 PE) that provides a powerful tool for simulating and analyzing enrichment designs with an eye towards incorporating them into existing clinical trials. ADDPLAN offers a leg-up to study sponsors eager to take advantage of the economic and patient safety benefits of an adaptive enrichment design without the need to bring in outside experts.

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Benjamin Hunting
Aptiv Solutions Blogging Team

The IMDRF, which was formed last year when the regulatory bodies that had previously been part of the Global Harmonization Task Force dissolved that group in favor of an industry-free association, has taken an interest in the development of what has been labeled the Regulated Product Submission standard, or RPS. This Health Level 7 electronic standard is intended to reduce the amount of documentary redundancy that can accumulate during the drug and medical device submission processes. By adopting an XML-based design (also known as Refined Message Information Model, or R-MIM), authorities can more easily parse complex submissions.

The further advantage of moving to a RPS standard is that it can be applied not just to a single type of regulated product, but rather across all medical devices and drugs requiring FDA attention. Furthering the efficiencies made possible by RPS is the attempt by the IMDRF to work with other international bodies currently investigating similar standards (such as the International Conference on Harmonization), which could lead to a one-format/multiple regulatory agencies system. This would allow the efficiencies currently sought by the FDA to be enjoyed by medical device manufacturers and drug development companies around the globe, with a dramatic reduction in the amount of paperwork and bureaucratic wrangling associated with a product submission.

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Benjamin Hunting
Aptiv Solutions Blogging Team

Adaptive design trials are gaining wider acceptance across the drug, medical device, and diagnostics industries and have the potential to increase development efficiency, productivity, and the probability of success in pivotal studies. Hear from key industry leaders as they share their expertise through presentations, discussions, and case studies.

The program examines the impact of adaptive design on the development process in the context of both simple and more sophisticated designs, and discusses the regulatory acceptance of these approaches. The Tufts Center for the Study of Drug Development recently facilitated a senior executive roundtable to discuss the adoption and impact of adaptive design and the findings of that session will be discussed.

Speakers include:

• Vladimir Dragalin, PhD, Senior Vice President, software development and consulting, Aptiv Solutions
• Philip T. Lavin, PhD, FASA, FRAPS, Executive Vice President, device programs, Aptiv Solutions
• Stella Stergiopoulos, Project Manager, Tufts Center for the Study of Drug Development
• Sue Jane Wang, PhD, Associate Director for adaptive design and pharmacogenomics, Office of Biostatistics, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA

For additional information and to register, visit http://www.raps.org/education-amp-training/raps-meetings-amp-education-calendar/adaptive-design-trials-june-2013.aspx.

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According to an article published by Clinica, a re-think of NCAR was prompted by a survey sent by the IMDRF to users in an effort to find out what was, and what wasn’t, working with how the initiative was being run. 18 questions in total were posed by the survey, and all 29 program users provided their feedback. On the positive side, NCAR was shown to be useful in providing a global perspective on important medical device safety issues. Unfortunately, more detailed responses indicated that instead of transmitting information concerning serious adverse events (SAEs), NCAR was more often being used as a simple communications tool between program users. In fact, field safety corrective actions were the most-frequent data transmissions through the NCAR network, discouraging program proponents who lamented the lack of risk assessment or background information absent from these communications. Furthermore, NCAR information was frequently not timely enough to impact safety decisions in a meaningful way.

What does the near-term have in store for NCAR? Medical device companies can expect that corrective action will be taken with regard to how quickly SAEs are transmitted, but more importantly, the program will most likely have its scope broadened in order to better service its users. The Clinica article specifically mentions interfacing NCAR with global registries, as well as adding information concerning inspections, compliance, license and certificates, and pre-market assessments to the mix on top of SAE data.

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Benjamin Hunting
Aptiv Solutions Blogging Team

Like many smaller markets, Egypt makes use of a list of ‘reference countries,’ that is to say nations whose regulatory bodies offer medical device regulations that are considered to be equivalent to those upheld by the CAPA. This list is now much longer than in the past, with every country in the European Union being added to each of the other major worldwide regions (U.S. and Canada, Australia, Japan).

Egypt is also allowing medical device manufacturers to skip declarations of conformity, biocompatibility test reports, and stability studies in technical file submissions. In addition, there is now a process in place that facilitates registration inquiries during an initial 10-day period, post-submission, for companies curious about the status of their application.

There are a few areas where the CAPA hasn’t lessened the burden of submitting a medical device for approval in the Egyptian market. All registration requests must meet regulatory requirements within 60 days of the initial registration date or they will be considered invalid. CAPA also demands that the first shipment of a sterile medical device, regardless of its point of origin, undergo an analysis by Egypt’s own National Organization for Drug Control and Research. The timetable for this process – i.e. how long it would take for the body to perform its analysis – has not been provided by CAPA.

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Benjamin Hunting
Aptiv Solutions Blogging Team

The principal purpose of the Medical Device Vigilance System is to improve the protection of health and safety of patients, users, and others by reducing the likelihood of reoccurrence of any such incidents elsewhere. This outcome is to be achieved by the evaluation of reported incidents and, where appropriate, dissemination of information, which could be used to prevent such repetitions or alleviate the consequences of such incidents. The Medical Device Vigilance System is also intended to facilitate a “direct, early and harmonised” implementation of FSCA across the member states where the device is in use, rather than relying on action taken on a country by country basis. The guidelines specifically point out that vigilance reporting may be more difficult for medical devices that do not generally come into contact with patients:

“For the majority of diagnostic devices, IVDs and IVF/ART* medical devices, due to their intended use, it can be difficult to demonstrate direct harm to patients, unless the device itself causes deterioration in state of health.”

“It may be difficult to determine if a serious deterioration in the state of a patient’s health was or could be the consequence of an erroneous result obtained with an IVD or a diagnostic device, the consequence of an inappropriate treatment of reproductive cells with an IVF/ART device or the consequence of an error by the USER or third party.”

In these cases, the guidelines seem to err on the side of caution, noting that in cases of doubt, a report should be submitted. The revised guidance (MEDDEV 2.12-1 revision 8) will be applicable as of July 2013.

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Gwen Darling
Aptiv Solutions Blogging Team

*In-Vitro Diagnostics and In-Vitro Fertilization/Assisted Reproductive Technologies

Under the current system, a re-registration requires the submission of a substantial amount of documentation, much of which duplicates information that was provided during the initial approval process. In order to reduce the burden on medical device companies seeking to re-register, the new draft proposal from the CFDA does not require the submission of technical information if there have been no changes which impact the safety or efficacy of the product in question.

Furthermore, if changes have been made to a medical device, only technical documentation related to those specific alterations is required to be submitted, along with a device vigilance report addressing adverse events associated with the product. Major changes, however, would require that the medical device be treated as a new product, which would in turn force it to go through a new product registration.

One of the primary motivations behind the streamlining of its medical device re-registration process is the desire by China to improve the speed at which innovative products reach the market. The CFDA is in the midst of pondering the establishment of a dedicated office that would exclusively handle innovative medical device submissions, with an eye towards creating a ‘fast-track’ approval channel for products which meet very specific requirements. In order to be eligible for this program the CFDA would require that a medical device make its global debut in China, be registered in China under an invention patent, demonstrate a ‘significant improvement’ over similar medical devices, and offer a full research and development history establishing its pioneering status in its field.

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Benjamin Hunting
Aptiv Solutions Blogging Team

The conference entitled ‘Practice of Adaptive Clinical Trials’ features a number of key experts from several Japanese universities as well as representatives from the Japanese pharmaceutical industry, the Japanese CRO industry and the Pharmaceuticals and Medical Devices Agency (PMDA), Japan. Leaders from these four groups will discuss the current status of adaptive trial adoption in Japan and how this could evolve over time.

Professor Wassmer’s keynote lecture is entitled ‘Lessons learned from Phase II adaptive dose-finding trials’. Adaptive dose finding trials are recognized by both industry and regulatory agency experts as the area where adaptive design can have a major impact on the product development process, not only in terms of trial efficiency but also in terms of enhanced probability of success by guiding selection of the appropriate dose for Phase III pivotal trials.

“Poor design of Phase II studies is a major reason for failure in later Phase III trials. Traditional dose-finding trials leave much room for improvement and Phase II dose-finding is the key area regulatory agencies see as benefitting most from adaptive designs,” says Professor Wassmer.

In a second lecture, Spiess will provide an overview of adaptive design incorporating a number of case studies that demonstrate the benefits of adaptive trials as well as the regulatory agency guidance available from the FDA and EMA.

“We are both honored and very excited to be part of this prestigious event at Tokyo University,” says Pat Donnelly, Chairman and CEO of Aptiv Solutions. “Adaptive design trials are rapidly gaining acceptance in the US and Europe, and it’s exciting to see the discussion continually advancing in Japan and other key countries.”

About Aptiv Solutions 

Aptiv Solutions is a global development services company that is focused on enhancing clinical trial decision-making, efficiency and productivity in the pharmaceutical, biotech and medical device markets. The company offers clients an extensive portfolio of innovative services including adaptive clinical trials, translational research services, regulatory services, pharmacovigilance, clinical staffing and the operational support of a global clinical research organization. Aptiv Solutions has more than 850 professionals in North America, Eastern & Western Europe, Israel, and Japan. Visit the website at www.aptivsolutions.com.

Contact:  Ryan Ferrell
Mobile:  +1 312.506.5202

Email:rferrell@harrisdmckinney.com

Contact:  Alan Zachary, Ph.D.
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Email:azachary@harrisdmckinney.com

Join industry experts from Roche, Novartis, Boehringer-Ingelheim, and others in a complimentary half-day seminar to discuss the impact and challenges of adopting an adaptive design strategy in early phase development.

Date: Tuesday May 28th 2013

Time: 12.00 to 18.00 pm

Location: Ramada Hotel, Basel, Switzerland.

Confirmed speakers and topics include:

• Ralf Bilke, Head of Protocol Challenge Committee, Boehringer Ingelheim – Integrating adaptive design into protocol development.
• Simon Day, Statistical Expert, Roche (ex MHRA) – Challenges of making correct and effective decisions in data-monitoring committees.
• Laurent Spiess, Vice President Adaptive Clinical Trials, Aptiv Solutions – Value and benefits of adaptive design trials.
• Stuart Bailey, Global Head Early Clinical Biostatistics, Novartis Oncology – Strategic impact of adopting adaptive dose-escalation across a phase 1 oncology portfolio.
•  Professor Andy Grieve, Senior Vice President Clinical Trial Methodology, Aptiv Solutions – Design & execution of Phase II adaptive dose-finding trials.

Click here for additional details and to register.

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Aptiv Solutions Blogging Team

Reston, Virginia, May 2, 2013 – Aptiv Solutions, a biopharmaceutical and medical device development services company and pioneer in adaptive clinical trial design, simulation and execution, announces a significant expansion of its medical device research capabilities in Europe. Most notably, the company announces the appointments of Mr. Bernard Sweeney as Senior Vice President, Medical Devices and Mr. Erdmann Zippel as Senior Director, Clinical Operations. Mr. Sweeney and Mr. Zippel will be based in Allschwil, Switzerland and Cologne, Germany, respectively. They will lead a rapidly growing team that specializes in providing regulatory and clinical research solutions to the medical device and diagnostics industry in Europe and includes more than a dozen new European specialists who joined since the start of 2013. 

Mr. Sweeney brings more than 20 years of experience that includes operational, strategic, regulatory and clinical trial expertise. He provides a strong skill set to assist medical device clients with product development, global regulatory requirements, and clinical trial management.

Most recently he served as Vice President at D-TARGET, the medical device division of Premier Research, where he supported corporate development activities.  Before that, he was Director of Healthcare at the British Standards Institute (BSI), a full-service Notified Body, where he led healthcare certification operations and oversaw a team of 80 technical specialists providing assessments, certifications and standards services to medical device and IVD companies. 

In industry, Mr. Sweeney worked as Managing Director for Femcare-Nikomed Ltd, a global organization of medical device companies with a portfolio of products in gynecology, general surgery and urology. He also held Director and senior management positions at Huntleigh Healthcare and Beiersdorf.

Mr. Sweeney holds a Bachelors of Pharmacy degree from the University of Manchester, Manchester Business School, and a Master of Business Administration degree from the Open University in the United Kingdom. He is a member of the Regulatory Affairs Professionals Society (RAPS) and previously served on the society’s European Advisory Committee.

Mr. Zippel brings more than 13 years of experience within the medical device, CRO, and biotech industries, and has specific expertise managing medical device clinical studies throughout Europe in the fields of cardiology, angiology, anesthesia/intensive care, orthopedics and neurology. He most recently served as Executive Director, Europe at D-TARGET, responsible for project management and resourcing of all EU projects, and overseeing a team of project directors, clinical research managers, clinical research associates, regulatory affairs managers, and quality assurance managers.

His industry experience includes senior clinical research positions at Laryngeal Mask Company Ltd., now a Teleflex company, where he supported the development of anesthesia, urology and orthopedic devices. At Biotronik, a market leader in the CRM business, he was involved in clinical research, training, regulatory and technical support activities for pacemaker, ICD, heart failure and telemedicine devices. Prior to joining industry in 2001, he spent 12 years as a registered nurse focused on hospital intensive care and anesthesia.

In addition to these positions, Aptiv Solutions has further added to its operational expertise in medical devices by hiring more than a dozen project managers, clinical research associates, and business development professionals with specific experience in supporting medical device clients in Europe. These hires complement the medical device team Aptiv Solutions has based in North America.

“I am pleased to welcome Bernard, Erdmann, and the rest of our new hires to our growing medical device team in Europe,” says Pat Donnelly, Chairman and CEO of Aptiv Solutions. “Their experiences and expertise in the medical device market, gained from roles in industry and as service providers, bring a unique perspective and will benefit our European clients who are seeking to develop and commercialize innovative medical devices and diagnostics.”

“In the complex and evolving medical technology landscape, Bernard’s and Erdmann’s experience in the international market and combined depth of knowledge of global device regulations and clinical research will be of significant benefit to our clients,” adds Luis Gutierrez, Executive Vice President and Chief Commercial Officer at Aptiv Solutions.

About Aptiv Solutions 

Aptiv Solutions is a global development services company that is focused on enhancing clinical trial decision-making, efficiency and productivity in the pharmaceutical, biotech and medical device markets. The company offers clients an extensive portfolio of innovative services including adaptive clinical trials, translational research services, regulatory services, pharmacovigilance, clinical staffing and the operational support of a global clinical research organization. Aptiv Solutions has more than 850 professionals in North America, Eastern & Western Europe, Israel, and Japan. Visit the website at www.aptivsolutions.com.

Media Inquiries

Contact:  Ryan Ferrell
Mobile:  +1 312.506.5202

Email:   rferrell@harrisdmckinney.com

Contact:  Alan Zachary, Ph.D.
Office:  +1 312.506.5220
Email:  azachary@harrisdmckinney.com