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DIA's Content Currents provides you with new and important global regulatory developments and their impact on pharmaceutical, biotechnology, and medical product development.

EDITION PUBLISHED: October 24, 2014

SECTION 1 FDA GUIDANCES & MAPPS

CDER List of Guidance Documents

CDER Guidances: New/Revised/Withdrawn through 6/30/14

The links above lead to the List of Guidance Documents (CDER) updated on July 7, 2014, and to CDER Guidances that are new, revised, or withdrawn through the second calendar quarter of 2014.

Guidance Agenda: Guidance Documents CBER is Planning to Publish During Calendar Year 2014 (PDF - 31KB)

CDRH FY 2014 Proposed Guidance Development

On October 20, 2014, FDA announced the availability of a draft guidance entitled “Two-Phased Chemistry, Manufacturing, and Controls (CMC) Technical Sections.” The purpose of this document is to provide recommendations to sponsors submitting CMC data submissions. For review efficiency, the Center for Veterinary Medicine (CVM) prefers that CMC information be submitted in a single technical section. However, there may be instances when a two-phased technical submission process is more beneficial to improve the overall time to drug approval. Sponsors may submit the phased CMC technical section as a single technical section or a two-phased technical section. This guidance describes the use of the two-phased technical section submission process.  Comments should be submitted by December 19, 2014.  [Federal Register]

33    On October 22, 2014, FDA announced the availability of the guidance entitled ‘‘Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection.” This guidance defines the types of actions, inaction, and circumstances that FDA considers to constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection for the purposes of making a drug adulterated. Among other things, FDA added examples that may constitute reasonable explanations for actions, inactions, or circumstances that could otherwise be considered delaying, denying, or limiting inspection, or refusing to permit entry or inspection. [Federal Register]

On October 22, 2014, FDA announced the availability of a draft guidance entitled ‘‘Migraine: Developing Drugs for Acute Treatment.’’  This guidance focuses on specific drug development and trial design issues that are unique to the study of drugs for the acute treatment of migraine. This guidance is intended to serve as a focus for continued discussions among the Division of Neurology Products, pharmaceutical sponsors, the academic community, and the public. Comments should be submitted by December 22, 2014. [Federal Register]

On October 24, 2014, FDA announced the availability of a draft guidance entitled ‘‘Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care.’’ The Office for Human Research Protections (OHRP), through which the draft guidance was released, is specifically addressing what risks to subjects are presented by research evaluating or comparing risks associated with standards of care, and which of these risks are reasonably foreseeable and should be disclosed to prospective research subjects as part of their informed consent.  Comments should be submitted by December 23, 2014. [Federal Register]

SECTION 2 FDA NOTES & RELATED NEWS

Updated List of CDER Key Officials Posted

CDRH Industry: New Resources Available on the eCopy Program for Medical Devices Submissions Webpage

FDA has updated its eCopy Program for Medical Device Submissions webpage to include additional resources.

FDA has posted five new video tutorials to supplement the existing Quick Reference Guide.  The videos explain how to successfully create an eCopy in real-time using this tool. They have also added a brand new tool for industry called the eCopies Validation Module.  The eCopies Validation Module is a free and voluntary tool that allows you to confirm that the eCopy you created meets the requirements.  After you download the tool, you choose the location of your eCopy and then run the tool.  If your eCopy does not meet the eCopy requirements, the tool will display the reason(s) why.  This will allow you the opportunity to address all eCopy issues prior to submitting it as part of your submission package to the CDRH Document Control Center (DCC). More at link above. (FDA.gov)

FDA Holds Webinar on Draft Guidance on Framework for Regulatory Oversight of Lab Developed Tests (LDTs)
On October 23, FDA held a webinar to provide an overview of the “Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) – Draft Guidance.” The draft guidance describes a risk-based framework for addressing the regulatory oversight of a subset of in vitro diagnostic devices (IVDs) referred to as laboratory developed tests (LDTs). It is intended to provide guidance to clinical laboratories that manufacture LDTs about how the FDA intends to enforce authorities that apply to such laboratories as medical device manufacturers under the Federal Food, Drug, and Cosmetic Act.

The webinar addressed clarification questions on the proposed framework, and slides have been posted at the link above. (FDA.gov)

DIA will hold a related panel discussion in connection with the October 28, 2014 Combination Products workshop and the October 29, 2014 Companion Diagnostics workshop:

Panel Session.  “Competing Regulatory Oversight of Investigational Tests, including LDTs, for Co-Development Programs.”  October 29, 2014.  Washington, DC. FDA, industry, IVD manufacturer, and laboratory stakeholders will discuss their perspectives on the impact of the FDA proposed LDT oversight framework on safety, clinical validity, innovation, and accessibility of investigational tests.   [DIA Companion Diagnostics]

FDA Among Collaborators on New Rare Disease Natural History Tool
The Von Hippel Lindau Alliance and NORD (National Organization for Rare Diseases) have created an online tool that enables people with the rare disease, Von Hippel Lindau disease, to enter information about their experiences with the disease, such as the progression of symptoms, and to add to this information at intervals throughout their lives. The natural histories of this and other rare diseases frequently are not fully understood because there are simply not enough cases that have been observed and studied. This lack of knowledge limits researchers’ ability to study rare diseases and develop new treatments. Knowledge of natural history is essential for developing more efficient clinical trial designs. It also could help reduce the length and cost of drug development and, possibly, contribute toward greater predictability of clinical development programs.

This tool is now helping researchers compile valuable data about the natural history of Von Hippel Lindau disease, and even better news is that this tool is universal.  Its features include protection of personal information, ease of use by patients or health care professionals; and accuracy checks for text and data.  More at link above.  (FDA.gov)

Patient-Focused Drug Development At 10: Where Does It Go From Here?
Summary: FDA may conduct more than the 20 required meetings by the end of fiscal year 2017, but how will the patient-focused drug development program find its place in helping generate new drugs?

Allowing a forum for patients to give FDA information about their disease has proven popular, but a question remaining for the patient-focused drug development program as it continues to grow is how that information will be used. To date, 10 FDA-sponsored, disease/disorder specific meetings have been held to receive patient input on their lives and experiences with the disease. “But at least one patient advocate has asked about FDA’s next steps, including how the meetings, experiences and opinions can lead to new treatments for the various diseases that have been covered.”

At the time of the establishment of the program, FDA said it would conduct the meetings focused on specific diseases in order to gain perspectives on existing treatments and unmet needs. Ideally, the information will help reviewers better understand the diseases and patient risk tolerance and inform approval decisions.

While not a formal FDA guidance on drug development, the agency expects the reports will help sponsors determine patients’ unmet needs as well as provide ideas for new outcome measures in clinical trials.

Some stakeholders already want to tweak the program in PDUFA VI to make FDA’s compilation of patient comments more systematic, rather than continue using an anecdotal process.  FDA also is allowing the program to grow outside the doors of its White Oak headquarters. A number of patient groups are planning their own patient-focused drug development meetings using a similar format as the FDA events. Agency officials have committed to attending them if they are held in the Washington D.C. area and agree with their schedules. More at link above. (Pink Sheet, paid subscription required)

FDA backs further study of kidney biomarkers
FDA issued its first Letter of Support for two kidney biomarkers identified by the Predictive Safety Testing Consortium (PSTC) of the Critical Path Institute (C-Path).

Elevated levels of the two biomarkers, osteopontin (OPN) and neutrophil gelatinase-associated lipocalin (NGAL) in urine were associated with renal tubular epithelial degeneration/necrosis in C-Path's animal studies. FDA encouraged investigators to conduct non-clinical and exploratory clinical studies to evaluate the relevance of OPN and NGAL measurements in determining kidney injuries.

A Letter of Support from FDA does not qualify a biomarker, but rather encourages further evaluation of a promising candidate biomarker.

To date, FDA, EMA and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) have qualified seven urinary biomarkers for kidney injury. They include kidney injury molecule-1, albumin, total protein, beta-2-microglobulin, cystatin C, clusterin and trefoil factor-3. (BioCentury)

User Fees For Biomarker Qualification Might Improve Study Designs
Industry wants more clarity from FDA on how confident a company must be in its biomarker before it can enrich a clinical trial based on that marker and stop evaluating biomarker-negative patients, even going so far as to suggest FDA might want to establish user fees and review goals to qualify biomarkers.

Firms are asking for more guidance on how sure a sponsor needs to be that it’s ruled out a potential benefit in the biomarker-negative population, particularly when a biomarker isn’t one simple precise point. Companies also want more guidance on what must be established about treatment effects in the biomarker-negative subgroup.

Unfortunately for industry, some of FDA’s statements indicate the agency might not be ready to give final answers on these questions, and Center for Drug Evaluation and Research Director Janet Woodcock said there is still much work to be done on developing the evidentiary criteria needed for biomarkers.

Briggs Morrison, chief medical officer at AstraZeneca PLC, said “we’ve actually done a pretty poor job in developing, qualifying and using biomarkers in drug development,” pointing out that there are 4,000 diseases that we now understand the molecular process of and yet under the FDA process only a “hand, maybe two handfuls,” of novel biomarkers have been qualified.

Morrison pushed for science-based but pragmatic approaches to define the evidentiary standards needed to use biomarkers in clinical trials.

“Imagine if there was a predictable pathway to biomarker approval with clear evidentiary standards for specific contexts of use. Perhaps the FDA could establish its own approval pathway with specified review cycle times including performance goals and procedures just as we have under the earlier subsets of PDUFA,” Morrison said.  More at link above.  (Pink Sheet, paid subscription required)


SECTION 3 AGENCY AND ADVISORY COMMITTEE MEETINGS

Patient-Focused Drug Development: Disease Area Meetings Planned for FY2013-2015

Panel Session.  “Competing Regulatory Oversight of Investigational Tests, including LDTs, for Co-Development Programs.”  October 29, 2014.  Washington, DC. FDA, industry, IVD manufacturer, and laboratory stakeholders will discuss their perspectives on the impact of the FDA proposed LDT oversight framework on safety, clinical validity, innovation, and accessibility of investigational tests.   [DIA Companion Diagnostics]
 
Public Meeting.  Patient-Focused Drug Development and Scientific Workshop on Female Sexual Dysfunction.   October 27-28, 2014.  White Oak Campus, Silver Spring, MD.  FDA is conducting a Patient-Focused Drug Development public meeting and scientific workshop on Female Sexual Dysfunction (FSD).  [Federal Register]

Day 1 – October 27th Patient-Focused Drug Development Public Meeting
FDA is interested in obtaining patient input on:

  1. The impact of the most common form of FSD, female sexual interest/arousal disorder (FSIAD) on daily life
  2. Patients’ views on currently available therapies to treat the condition

Day 2 – October 28th Scientific Workshop
The scientific workshop will include discussion on scientific challenges related to:

  1. Diagnosis of the condition for clinical trials and in clinical practice
  2. Ensuring valid patient-reported outcome measures for the key efficacy endpoints used in clinical trials

New:  First Annual Neonatal Scientific Workshop – Roadmap for Applying Regulatory Science to Neonates.  October 28-29, 2014.  Silver Spring, MD.  The purpose of this scientific workshop is to accelerate the development of therapeutics for the neonatal population. The workshop will also serve to map out the priorities of this new consortium devoted to applying regulatory science to the neonatal population, as well as ensuring that the leading academic experts in the US, Canada and Europe, interested companies, regulatory agencies, patient groups, NIH institutes, and non-profit organizations, all have an opportunity to shape priorities and eventually join the new consortium. [FDA.gov]

Public Meeting.  Development and Regulation of Abuse-Deterrent Opioid Medications.  October 30-31, 2014.  Silver Spring, MD.  The purpose of the meeting is to discuss the development, assessment, and regulation of abuse-deterrent formulations of opioid medications. The meeting will focus on scientific and technical issues related to the development and in vitro assessment of these products, as well as FDA’s approach towards assessing the benefits and risks of all opioid medications, including those will abuse-deterrent properties. [FDA.gov]

Public Advisory Committee Meeting. Risk Communications Advisory Committee. November 3-4, 2014. White Oak Campus, Silver Spring, MD.  The Risk Communication Advisory Committee will discuss methods for effective risk communication with a focus on messages about the importance of eating adequate amounts of fish, while avoiding certain fish with higher amounts of methyl-mercury. These messages are especially important for women who are pregnant or nursing, or for anyone who prepares food for young children. [Federal Register]

Clinical Investigator Training Course. November 4-6, 2014. College Park, MD.  This training course, a co-sponsored event of FDA CDER and Duke University Office of Continuing Medical Education, is intended to provide clinical investigators with expertise in the design, conduct, and analysis of clinical trials; improve the quality of clinical trials; and enhance the safety of trial participants.  [Federal Register]

Public Advisory Committee Meeting. Cellular, Tissue and Gene Therapies Advisory Committee. November 6, 2014. White Oak Campus, Silver Spring, MD. The committee will discuss the draft guidance for industry entitled ‘‘Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products’’ and the Dear Gene Therapy IND or Master File Sponsor Letter.  [Federal Register]

Science Advisory Board to the National Center for Toxicological Research (NCTR) Advisory Committee Meeting.  November 6-7, 2014. NCTR, Jefferson, AR. On November 6, a Center-wide update on scientific initiatives and accomplishments during the past year will be presented. An overview of the Division of Microbiology Subcommittee and the Subcommittee Site Visit Report will be presented.  On November 7, 2014, the Office of the Chief Scientist will update the SAB on their research needs, and discuss opportunities for collaboration to help address these needs.  The Center for Biological Evaluation and Research, the Center for Drug Evaluation and Research, the Center for Devices and Radiological Health, the Center for Veterinary Medicine, the Center for Tobacco Products, the Office of Regulatory Affairs, and the Center for Food Safety and Applied Nutrition will each briefly discuss their Center-specific research strategic needs. [Federal Register]

Public Meeting and Request for Comments.  Regulatory Science Considerations for Software Used in Diabetes Management.  November 13, 2014.  White Oak Campus, Silver Spring, MD. The goals of this public workshop are to foster greater stakeholder collaboration in the area of diabetes device interoperability and to seek input from the clinical community, academia, government, industry, and other stakeholders regarding usability considerations for appropriate information consumption (e.g., notifications, indicators, data, and displays) based on user skill and knowledge.  [Federal Register]

Science Board to the Food and Drug Administration Advisory Committee Meeting.  November 19-20, 2014. White Oak Campus, Silver Spring, MD. On November 19, the Science Board will review the existing nonclinical and clinical data related to the use and potential toxicity of anesthetics and sedation drugs in the pediatric population. The Science Board will be asked to make recommendations on steps the FDA should take to further evaluate and to mitigate the risks associated with the use of these drugs in the pediatric population and mechanisms to best communicate with the public regarding this issue. On November 20, among the agenda items will be consideration of a request to form a new subcommittee to evaluate the Centers of Excellence in Regulatory Science and Innovation program. [Federal Register]

Public Workshop. Brain-Computer Interface Devices for Patients With Paralysis and Amputation. November 21, 2014.  White Oak Campus, Silver Spring, MD.  The purpose of this workshop is to obtain public feedback on scientific, clinical, and regulatory considerations associated with BCI (Brain-Computer Interface) devices. Ideas and suggestions generated during this workshop may facilitate development of draft guidance to provide our initial thoughts regarding the content of premarket submissions for emerging BCI technologies to help speed development and approval of future submissions.  [Federal Register]    On September 30, 2014, FDA released a discussion paper in preparation for this workshop.  [FDA.gov]

Public Advisory Committee Meeting. Anesthetic and Analgesic Drug Products Advisory Committee. November 24-25, 2014. White Oak Campus, Silver Spring, MD. The committee will discuss the risk of serious neurologic adverse reactions associated with epidural steroid injections (ESI) administered to reduce inflammation for pain management. The committee will also consider the efficacy of ESI and the overall risk benefit balance of injecting steroids in the epidural space to treat pain. These considerations will assist the FDA in its discussions of possible regulatory options, including but not limited to changes to the product labeling. [Federal Register]

New:  Public Advisory Committee Meeting. Blood Products Advisory Committee. December 2-3, 2014. White Oak Campus, Silver Spring, MD. On December 2, 2014, the Committee will meet in open session to hear scientific data related to reconsideration of the current blood donor deferral policy for men who have had sex with another man (MSM) even one time since 1977. An informational presentation will be made regarding the emergence of chikungunya virus infections in the Western Hemisphere and potential implications for blood transfusion safety. On December 3, 2014, the Blood Products Advisory Committee will be seated as a device classification panel. In open session, the panel will discuss the appropriate device classification of blood establishment computer software (BECS) and accessories to BECS. [Federal Register]

New:  Public Advisory Committee Meeting. Anti-Infective Drugs Advisory Committee. December 4, 2014. University of Maryland University College, Hyattsville, MD.  The committee will discuss issues related to clinical development programs and clinical trial designs for antibacterial products for the treatment of patients with serious bacterial infections for which there are limited or no therapeutic options. [Federal Register]

Meeting. Realizing the Benefits of the Unique Device Identifier in Health Care.  Office of the National Coordinator and Pew Charitable Trusts.  December 9, 2014. Washington, DC. This meeting will present discussion on the benefits and challenges of integrating the unique device identifiers (UDI) into clinical care, registries, the supply chain, and other facets of health care delivery. [FDA.gov]

New:  Public Workshop. Seventh Annual Sentinel Initiative. February 5, 2015.  Washington, DC.  Convened by the Engelberg Center for Health Care Reform at the Brookings Institution and supported by a cooperative agreement with FDA, this 1-day workshop will bring the stakeholder community together to discuss a variety of topics on active medical product surveillance. There will also be a live webcast for those unable to attend the meeting in person. [Federal Register]


SECTION 4 OTHER REGULATORY AUTHORITIES & ORGANIZATIONS

PCORI: Help Shape Our Plan for Peer-Reviewing and Making Our Primary Research Results Publicly Available
The Patient-Centered Outcomes Research Institute (PCORI) seeks your comments on its draft process for the peer review and public release of our primary research findings. This process is part of PCORI’s broad dissemination and implementation plan to put knowledge gained from patient-centered outcomes research (PCOR) into practice.

The process aims to address fundamental questions about how PCORI will assess the scientific integrity of its research results and share them in timely, meaningful and useful ways with patients, clinicians and other clinical care decision makers.

Your input is a vital part of developing this process. Regardless of the role you play in our healthcare system – from research to clinical care – your comments will help PCORI determine the processes needed to ensure its research results, and how PCORI shares them with the community, are relevant and trustworthy.  

Comments should be submitted by November 7, 2014.  More information at title link above. (PCORI.org)

GAO Issues Call for Nominations to Fill PCORI Methodology Committee Seat
The U.S. Government Accountability Office (GAO) has issued a call for nominations to fill an open seat on the Patient-Centered Outcomes Research Institute (PCORI) Methodology Committee.

PCORI’s 17-member Methodology Committee is responsible for developing and updating methodological standards and guidance for the conduct of patient-centered comparative clinical effectiveness research (CER). The committee issued the PCORI Methodology Report last year to provide context for 47 PCORI Methodology Standards, minimal requirements for the conduct of scientifically valid patient-centered CER that the committee endorsed in May 2012.

GAO will accept letters of nomination and resumes submitted via either email or mail by Monday, Nov. 17. Information is available at the link above.  (PCORI.org)

Scientists Say National Alzheimer's Plan Research Milestones Must be Strengthened to Meet Primary Goal by 2025 Deadline
The U.S. government has initiated a major effort to prevent and effectively treat Alzheimer’s disease by 2025. However, a workgroup of nearly 40 Alzheimer’s researchers and scientists says the research milestones in the U.S. Government’s National Plan to Address Alzheimer’s Disease must be broadened in scope, increased in scale, and adequately funded in order to successfully achieve this goal. A series of proposals by the workgroup to enlarge and strengthen the Plan are published today in Alzheimer’s & Dementia: the Journal of the Alzheimer’s Association.

According to the authors of the newly published article, who include U.S.-based academic and industry scientists across all disciplines of Alzheimer’s research, “Many prominent investigators believe the prospect of delaying the onset of disabling symptoms within a decade is an attainable goal, provided we can surmount several scientific, administrative, and most importantly, financial impediments.”   The authors continue, “Inadequate funding remains the single most important impediment to progress in achieving the research goal of the National Plan.”  More at title link above.  (Alzheimer’s Association)

More Data, More Progress: ALS Researchers Debut Shared Database
Thanks to an enormous effort to collect and comingle data from 17 ALS clinical studies, researchers can now access thousands of patient records to understand the disease’s natural progression, hunt for biomarkers, and plan better therapeutic trials. Project organizers from the nonprofit Prize4Life in Cambridge, Massachusetts, and the Neurological Clinical Research Institute at Massachusetts General Hospital (MGH) in Boston, describe the Pooled Resource Open-Access ALS Clinical Trials database (PRO-ACT) in the October 8 Neurology online. In this paper, first authors Nazem Atassi and James Berry of MGH also offer a few examples of how the PRO-ACT data can be mined.

Typically, data from trials of unsuccessful drugs languish in file drawers or company vaults. Senior author Melanie Leitner, formerly of Prize4Life and now at Biogen Idec in Cambridge, Massachusetts, and colleagues have brought that valuable data out into the open. The project, a collaboration with the Northeast ALS Consortium, was funded by the ALS Therapy Alliance.

The Critical Path Institute has organized a similar effort for Alzheimer’s disease called C-Path Online Data Repository.

PRO-ACT currently contains the records from 8,635 people who participated in 16 Phase 2 or 3 trials and one observational study. Nearly 5,000 of those records list the ALS-Functional Rating Scale (ALS-FRS) scores, a standard measure for disease progression. More than 3,000 include date of death, because the person died while the trial was ongoing. More than 7,000 records indicate whether the patient took riluzole, the only treatment approved for ALS. Other data points include blood tests, lung capacity, and family and medical histories.

The organizers are further curating PRO-ACT, Zach said. In November, data on adverse events and concomitant medications will be added.  More at link above. (Alzheimers Research Forum)

NIH announces grants for frontotemporal degeneration research
The National Institutes of Health will award three large, five-year projects on a specific form of dementia, known as frontotemporal because of the areas of the brain that are affected. The projects, funded by the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA) and the National Center for Advancing Translational Sciences (NCATS), announced today total more than $5.9 million for 2014.

Approximately 50,000 Americans live with frontotemporal degeneration, or FTD, which causes severe behavioral changes and problems with language and cognition. As the disease progresses, individuals have difficulty planning activities, interacting with others and caring for themselves.

The grants cover a wide spectrum of FTD research, from fundamental discoveries of the genetics behind this disorder to testing potential therapies in patients. It is hoped that these projects will provide answers and new avenues of treatment for this devastating condition. “The projects aim to advance our understanding of frontotemporal degeneration by improving diagnosis, identifying preventive strategies and providing new insights into the genetics underlying this complex disorder,” said Margaret Sutherland, Ph.D., program director at NINDS. More at link above. (NIH.gov)

NIH Ebola Update: Working Toward Treatments and Vaccines
Updated Oct. 22, 2014: The National Institutes of Health (NIH) today announced the start of human clinical trials of a second Ebola vaccine candidate at the NIH Clinical Center in Bethesda, MD. In this early phase trial, researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) are evaluating the vaccine, called VSV-ZEBOV, for its safety and ability to generate an immune response in healthy adults who receive two intramuscular doses, called a prime-boost strategy.

The Walter Reed Army Institute of Research is simultaneously testing the vaccine candidate as a single dose at its Clinical Trials Center in Silver Spring, MD. VSV-ZEBOV, which was developed by researchers at the Public Health Agency of Canada’s National Microbiology Laboratory, has been licensed to NewLink Genetics Corp. through its wholly owned subsidiary BioProtection Systems, both based in Ames, Iowa.

Early human testing of another Ebola vaccine candidate, co-developed by NIAID and GlaxoSmithKline, began in early September at the NIH Clinical Center. Initial data on that vaccine’s safety and ability to generate an immune response are expected by the end of 2014. More at link above. (NIH.gov)

PhRMA Launches Access Better Coverage
Pharmaceutical Research and Manufacturers of America (PhRMA) launched Access Better Coverage.org, a new website designed to educate consumers about the ABCs of health coverage and access to prescription medicines.

The new site introduces important resources to help people better understand how health insurance works and what to expect from their coverage, including a series of white board videos explaining basic insurance terms like deductibles, copays and coinsurance, and how formularies and tiers work.

While health insurers apply a range of tools to try to manage health care costs, in some cases the tools put a burden on patients and their providers. A new video featured on the site walks through these possible hurdles and the resources at AccessBetterCoverage.org may help patients overcome them.

“We know health coverage can be confusing and overwhelming – particularly for those purchasing it for the first time – so we wanted to create a simple, straightforward resource to help demystify the process and equip patients to make coverage decisions that are right for them,” said PhRMA President and CEO John J. Castellani. “Our primary goal is to ensure patients have access to the health treatments and services they need.”

The site also features an interactive glossary of health care terms, news updates, research and primers on coverage basics helping consumers better understand this complex piece of the health care system.  More at link above. (PhRMA.org)

$840M Plan Unveiled to Boost Transitions to Outcome-Based Healthcare
If healthcare providers need another reason to move from fee-for-service delivery models to those based on patients’ health outcomes, the US Department of Health and Human Services (HHS) just provided one: an $840 million initiative, most of it grants, to help fund the cost of making the transition.

HHS Secretary Sylvia M. Burwell yesterday unveiled a program that will allow successful applicants to receive federal dollars to help them “rethink and redesign their practices,” while moving toward delivery models based on coordinated care and improving population health, according to a department statement.
 
The plan seems tailor-made to boost efforts by accountable care organizations (ACOs), which were created by the 2010 Patient Protection and Affordable Care Act (ACA) to allow entities of hospitals, practice groups, health plans, and other medical providers work together to improve health and patient satisfaction – and find savings – across a population. ACOs that make the grade, based on quality measures from the Centers for Medicare and Medicaid (CMS), are eligible for higher reimbursements from Medicare.

According to the HHS announcement, strategies that the new program hopes to promote include:

  • Giving doctors better access to patient information, including information on prescription drug use to help patients stick with medication schedules;
  • Expanding the ways patients can communicate with the team of clinicians taking care of them;
  • Improving the coordination of patient care by primary care providers, specialists, and the broader medical community; and
  • Using electronic health records on a daily basis to examine data on quality and efficiency.
More at link above. (American Journal of Managed Care)

Ensuring Patient Privacy in Data Sharing for Post approval Research
Post approval studies of drugs and devices are essential to identify late adverse events, but patients' privacy must be protected when EMR data are shared. This article discusses ways to balance the need for high-quality post approval information and respect for patients' privacy. (NEJM, article for subscribers only)

Goals of the federal Health IT Safety Center
Goals for the new federal health Information technology safety center, an idea initially proposed by the Institute of Medicine in a report published in November 2011, are outlined in a new article published this week the Journal of the American Medical Informatics Association.

While its functions are still being defined, the safety center is envisioned as a public-private entity working with key administrative and policy stakeholders, healthcare organizations and HIT vendors.

The goals of the Health IT Safety Center include: (1) facilitate creation of a nationwide ‘post-marketing’ surveillance system to monitor HIT related safety events; (2) develop methods and governance structures to support investigation of major HIT related safety events; (3) create the infrastructure and methods needed to carry out random assessments of HIT related safety in complex HCOs; and (4) advocate for HIT safety with government and private entities. The convening ability of a federally supported HIT Safety Center could be critically important to our transformation to a safe and effective HIT enabled healthcare system.  More at link above. (Fierce Health IT)

Karen DeSalvo steps down from ONC post; Jacob Reider to leave in November
Karen DeSalvo will step down from her role as National Coordinator for Health IT, effective immediately, to serve as Acting Assistant Secretary for Health at the U.S. Department of Health and Human Services at the behest of HHS Secretary Sylvia Mathews Burwell, an ONC spokesperson confirmed to FierceHealthIT on Thursday afternoon. In her new role, DeSalvo will work with Burwell on "pressing health issues, including becoming a part of the department's team responding to Ebola," the spokesperson said in an email.

Lisa Lewis, ONC's chief operating officer, will serve as Acting National Coordinator, according to ONC.

Deputy National Coordinator Jacob Reider also will leave ONC in late November, Reider confirmed to FierceHealthIT late Thursday.

"In light of the events that led to Karen's announcement today--it's appropriate now to be clear about my plans, as well," Reider said in an email to ONC staffers and sent to FierceHealthIT. "With Jon White and Andy Gettinger on board, and a search for a new Deputy National Coordinator well underway, I am pleased that much of this has now fallen into place--with only a few loose ends yet to be completed. I'll remain at ONC until late November, working closely with Lisa as she assumes her role as Acting National Coordinator."  More at link above. (Fierce HealthIT)

DHS to investigate med devices, hospital equipment for cybersecurity issues
Medical devices and hospital equipment are under investigation by the U.S. Department of Homeland Security after suspected cybersecurity flaws that could allow the tools to be hacked, according to a Reuters article.

The products--which include an infusion pump from Hospira Inc. and implantable heart devices from Medtronic Inc. and St Jude Medical Inc.--are under review by DHS' Industrial Control Systems Cyber Emergency Response Team, according to the article.

However, no instances of hackers attacking patients through the devices are known, according to sources cited in the article. Still, DHS has concerns that the tools could be activated remotely, and is working with manufacturers to identify and repair software bugs and vulnerabilities. More at link above. (Fierce HealthIT)

Caremark to Charge Extra Co-Pay at Pharmacies Selling Cigarettes
Last month, CVS Health purged its 7,700 pharmacies of tobacco products in a gambit to embrace a commitment to improving public health and generate goodwill. But the move comes with a price – an estimated $2 billion in annual sales will be sacrificed.

Now, the company is hoping to find a way to compensate for that bet. Its Caremark pharmacy benefits manager, which is one of the largest in the U.S., will soon require some customers to make an extra co-payment, in some cases up to $15, on any prescription that is filled at a pharmacy selling cigarettes and other tobacco products, according to sources.

As a result, CVS and other pharmacies that do not sell tobacco products, but do participate in a network managed by Caremark – typically, for health plans and employers – will have an extra incentive to attract or retain customers. Participating pharmacies, including some large chains, that do sell tobacco products will be at a disadvantage. More at link above. (Pharmalot)

Private Insurers Squeezing Devices Companies in Bid to Limit Costs
Expect medical device companies to feel the squeeze from the advent of reference pricing, whereby patients must bear procedures' expenses that exceed a predetermined threshold.

The California Public Employees' Retirement System (CalPERs) pioneered this cost-saving technique more than three years ago, setting a reference price of $30,000 for elective hip and knee surgeries. Patients must pay the full cost for charges beyond that limit, and the charges don't count toward their annual maximum out-of-pocket limit, Kaiser Health News reports.

Cataract surgery, colonoscopies and arthroscopic surgery now have reference prices too, at least for the 1.4 million CalPERs members. And others are following suit. Among employers with more than 10,000 employees, the percentage using reference pricing increased from 10% to 15% between 2012 and 2013, says Kaiser Health News.  More at link above.  (Fierce Medical Devices)

EMA encourages companies developing Ebola treatments and vaccines to apply for orphan designation
On October 20, 2014, the European Medicines Agency (EMA) announced that it encourages developers of treatments or vaccines against Ebola to apply for orphan designation. Medicines with recognized orphan status have access to a range of incentives to stimulate development and facilitate placing on the market. This includes free scientific advice from EMA, fee waivers and 10 years of market exclusivity once the medicine is authorised.

Applications for orphan designation of Ebola medicines will be treated as a priority and EMA has committed to fast-tracking their evaluation.

EMA has been collaborating very closely with the United States Food and Drug Administration (FDA) on orphan medicines over many years. Developers of Ebola medicines are encouraged to submit applications for orphan designation to EMA and FDA in parallel to help speed up the development process for these medicines globally. Both Agencies will be sharing information on the applications received and their assessment to facilitate understanding of data requirements for the relevant applications.  More at link above. (EMA.europa.eu)

EMA ready to start assessment of Ebola vaccines and treatments as soon as data are made available
During the past months, the European Medicines Agency (EMA) has put in place a system to give the best possible scientific advice to companies that are currently developing possible vaccines and/or treatments to fight Ebola virus disease.

The Agency has also established a form of rolling review that allows experts to continuously assess incoming data and develop increasingly robust scientific opinions based on the additional data provided during the process. The initial review and subsequent updates will be shared with healthcare decision-makers in the most affected and other countries. This will enable them to take informed decisions on whether and how they want to use the vaccines/medicines in the current Ebola outbreak taking into account their specific situation.

“We are ready and keen to assess data as soon as companies start submitting them,” explains EMA Executive Director Guido Rasi. “We have put in place regulatory processes that allow the best experts from across Europe to accelerate the assessment of data once we receive them.” More at link above. (EMA.europa.eu)

European Medicines Agency completes review of polymyxin-based medicines
The European Medicines Agency (EMA) has reviewed the safety and effectiveness of products containing the antibiotics colistin or colistimethate sodium (known as polymyxins) and recommended changes to their product information to ensure safe use in the treatment of serious infections that are resistant to standard antibiotics.

Polymyxin-based products have been available since the 1960s, but their use quickly decreased due to the availability of antibiotics with fewer potential side effects. Due in part to this limited use, colistimethate sodium has retained activity against a number of bacteria which have become resistant to commonly used antibiotics. This has led to a resurgence in recent years in the use of polymyxins in patients with few other options. However, current experience has raised concerns that the existing product information, in particular relating to dosing and the way the medicine is handled in the body (pharmacokinetics), might need updating.

The Agency’s Committee for Medicinal Products for Human Use (CHMP) reviewed the available data about the pharmacokinetics, effectiveness and safety of these medicines. They concluded that injection or infusion (drip) of colistimethate sodium should be reserved for the treatment of serious infections due to susceptible bacteria, in patients whose other treatment options are limited. Colistimethate sodium may also be given by inhalation or in a nebulizer to treat ongoing (chronic) infections with the bacterium Pseudomonas aeruginosa in patients with cystic fibrosis.

The CHMP opinion will now be forwarded to the European Commission, which will issue a final decision in due course.  More at link above.  (EMA.europa.eu)

Insiders say NICE is being encouraged to be more favourable to industry
Committees of the UK National Institute for Health and Care Excellence (NICE) are being encouraged to be more favourable to the drug and device industries, The BMJ has been told.

The concerns have been raised since a change in the minister with responsibility for NICE. On 15 July this year George Freeman took over this role when he was appointed as parliamentary undersecretary of state for life sciences at the Department for Business, Innovation and Skills and the Department of Health for England. It is a new ministerial post with a remit to accelerate innovation.

NICE sources are concerned that the change in minister responsible for the institute could lead to greater pressure to allow doctors to prescribe drugs before NICE has appraised them. The sources also told The BMJ they were worried about pressure to be more lenient in the interpretation of evidence.

Before becoming a Conservative MP Freeman had a long career in biomedical venture capital and ran the specialist translational medicine consultancy 4D Biomedical. He was also chief executive officer of the Cambridge start-up company Amedis Pharmaceuticals and before that the director of early stage ventures at the venture capital fund Merlin Biosciences.

Sources say it is as yet unclear how he will interact with NICE. In September this year Freeman told the Commons debate that it was “vital” for people to have access to new and promising drugs. He added, “A central part of my mission as the UK’s first minister for life sciences—an opportunity that reflects the government’s commitment and the prime minister’s personal commitment to this agenda—is to accelerate the discovery, design, and adoption of new drugs in the NHS, making the UK the best place in the world to discover and design 21st century healthcare technologies.”  More at link above.  (British Medical Journal)

WHO Call for Comments: Statement on Public Disclosure of Clinical Trial Results
In a recent statement, the World Health Organization reiterated its position that “The registration of all interventional trials is a scientific, ethical and moral responsibility,” and cited data indicating a substantial number of randomized controlled trials remain unreported several years after study completion. Further, concerns have been raised that there may be selective publication of trials dependent on their results.  

The statement indicates that any clinical trial is to be registered in a free access, searchable registry before the first subject receives the first medical intervention.  All trial registry sites are to be updated to include final enrollment numbers and date of study completion.  The main findings of the trial are to be submitted for publication in a peer reviewed journal within 18 months of study completion or made available by other public means within 30 months, and the key outcomes are to be posted to the results section of the registry.  WHO has called for comments by November 15, 2014. More at link above.  (WHO)


SECTION 5 LEGAL AND COMPLIANCE

IRB Process Streamlining Expected In 21st Century Cures Bill
Summary: A move toward centralized institutional review board approval of study protocols could reduce clinical trial delays; House Energy and Commerce Committee also is looking at optimizing use of real-world data in the post-market setting.

Reforming the institutional review board process, with an eye toward streamlining clinical trials, is expected to be a focus of forthcoming draft legislation from the House Energy and Commerce Committee’s 21st Century Cures initiative.

The legislation could provide an opening to move toward a more centralized IRB process and reduce the clinical trial delays associated with the need to get approval from local IRBs affiliated with clinical trial sites.

Congressional staffers highlighted some of the ideas they’ve been hearing that seem likely to make their way into legislation. Among these are streamlining the clinical trial process and making better use of real-world data:

A very common theme that’s been talked about is centralized IRBs.  Although the discussion took place in the context of medical device studies, it seems likely that any move away from local IRB approval and toward a more centralized approach would also extend to the clinical testing of drugs and biologics.

Another idea aimed at modernizing and streamlining the clinical trial process that the Energy and Commerce Committee finds “intriguing” is to bring in more real-world clinical practice data after approval so as not to delay a product from coming to market, said Clay Alspach, chief health counsel for the committee.  More at link above.  (Pink Sheet, paid subscription required)

21st Century Cures: Path2Cures Roundtable in Virginia October 22
Energy and Commerce Committee members have taken the bipartisan 21st Century Cures initiative around the country with roundtables in Colorado, Pennsylvania, Massachusetts, New Jersey, Florida, Ohio, Michigan, and North Carolina. The ongoing conversations have been instrumental in building support for the important effort. This week, Rep. Morgan Griffith (R-VA), along with Rep. Phil Roe, M.D. (R-TN), took the conversation to Virginia. Health leaders, innovators, and academics joined Griffith at the Edward Via College of Osteopathic Medicine in Blacksburg, Virginia, on Wednesday, October 22, 2014.

The two-hour discussion between the two Congressmen and 12 panelists went beyond the FDA approval process to cover a variety of topics: the need for health care providers to better share information about their patients; concerns about gaps in Medicare funding for telemedicine; problems with the patent process; and how to best balance the latest innovations with the more low-tech practice of encouraging patients to eat well, stop smoking and exercise more.

With more drugs and medical devices being developed for conditions that were once considered incurable, several panelists called for more resources and a change in the regulatory culture at the FDA.

“It’s not just a matter of telling them to do their job and do it faster. … I think they’re understaffed and underfunded,” said David Ayares, head of U.S. operations and chief scientific officer for Revivicor Inc., a regenerative medicine company.

Dr. Bob Meyer, director of the Virginia Center for Translational and Regulatory Sciences at the University of Virginia, countered that it’s not so much a matter of understaffing as it is having the right kind of staff, including scientists with a better understanding of new technologies and different approaches. “It’s a matter of maturing the science,” he said. More at link above.  Video available here  (Energy & Commerce)

Congressman Brings 21st Century Cures Roundtable to Mt Lebanon PA
On October 23, Congressman Tim Murphy (PA-18) hosted a public discussion with local disease advocates and medical innovators to discuss ways to improve the discovery, development, and delivery of new medications and treatments. Southwestern Pennsylvania advocates from organizations including the Multiple Sclerosis (MS) Society, the Arthritis Foundation, and the American Cancer Society, as well as Cecil Township-based generic drug manufacturer Mylan, discussed current regulatory and non-governmental barriers to new life-saving therapies and ways to improve the FDA approval process.

Speaking from the federal perspective on bringing new therapies to market was Dr. Pamela McInnes, Deputy Director of the National Center for Advancing Translational Sciences (NCATS), a division of the National Institutes of Health dedicated to finding better ways to translate clinical observation into treatments, procedures, and medications. More at link above. (Energy & Commerce)

Upton Responds to Latest Confirmed Ebola Case in the United States
House Energy and Commerce Committee Chairman Fred Upton (R-MI) issued a statement regarding the latest confirmed case of Ebola in the United States, a doctor in New York who recently returned from Guinea where he had treated patients for Doctors Without Borders. A group of Republican committee members yesterday sent a letter to President Obama, Ebola Response Coordinator Ron Klain, Health and Human Services Secretary Sylvia Burwell, and Secretary of Homeland Security Jeh Johnson seeking a detailed plan to address the ongoing Ebola crisis, prevent further spread of the virus, and ensure the United States public health system is capable of identifying and treating patients.  More at link above.  (Energy & Commerce)

Senate Lawmaker Eyes Hearing on the Cost of Hepatitis C Treatments
Responding to the ongoing controversy over the prices for new hepatitis C treatments, U.S. Sen. Bernard Sanders (I-Vt.) will probably hold a hearing – possibly before the year ends – to examine how the cost is affecting the U.S. Department of Veterans Affairs, according to his spokesman. Sanders is chairman of the Senate Committee on Veterans’ Affairs.

His interest in a hearing comes as the expense of these medicines helps fuel a national debate over the rising cost of prescription drugs. New hepatitis C treatments, in particular, have caused a ruckus, because they promise cure rates exceeding 90%, which is prompting a sudden surge in prescribing – and subsequent concerns over the effect on insurance budgets.

The timing for a hearing, however, remains uncertain. The spokesman says a hearing may occur following the upcoming midterm elections on Nov. 4, “but it’s really up in the air.” More at link above. (Pharmalot)


SECTION 6 SOURCES REVIEWED FOR THIS NEWSLETTER

A partial listing of sources reviewed for this newsletter:  AdvaMed Smartbrief; AHRQ Newsletter; Alzheimers Association; Alzheimers Research Forum Newsletter; BioCentury; Biopharma Reporter; BIOtechNow; CDISC Monthly Newsletter; CER Daily Newsfeed (NPC); Daily Dose (Becker); DIA Daily; Drug Daily Bulletin;  EMA website; EP Vantage; Evaluate Pharma; Eye on FDA; FDA.gov; FDA Law Blog; Federal Register Table of Contents; Fierce Medical Devices; Fierce Pharma; Fierce Vaccines; FDLI Smartbrief; Genomeweb; Health Industry Washington Watch; Government Health IT; Health IT Security; Institute of Medicine News; MedCityNews; Medical Device Daily; Medical Device & Diagnostic Industry; MedPage Today; NPC Bulletin; Nutra Ingredients USA; Pharmabiz; Pharmafile; Pharma IQ; PharmaTimes; PhRMA website; PM Live; Policy and Medicine (newsletter); Regulatory Focus; RegLink News; US FDA Daily Digest Bulletin.