July 28, 2015

Big Pharma Goes Big for Big Data

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

When it comes to data, big pharma knows what big pharma likes, according to a new survey of giant pharmaceutical companies that included AstraZeneca, Merck, Pfizer and Boehringer Ingelheim. The winners in the data sweepstakes? Claims, electronic health records, health outcomes, real world studies, and registries.

However, no flavors of online or machine-generated data were rated highly by a majority in the project, “Big Data in Pharma,” conducted by Best Practices LLC. Eleven companies and twelve leaders were engaged in the benchmark study designed to produce reliable industry metrics on future and current trends for big data utilization across medical and commercial groups.

Post-launch and customer segmentation studies represented the most common big data projects at play today, with a majority of participants saying that partnerships with payers and data aggregators were “highly impactful.” Health systems were also perceived as valuable partners in each segment.

compounded pillsMedical teams also tended to find more value across data sources when compared to analytics in other functions, the survey found. Best Practices also conducted seven deep-dive executive interviews with selected benchmark participants.

While the majority (58%) reported leveraging a dedicated big data team, it’s somewhat surprising that the remainder said their analytics efforts weren’t centralized to that degree. Less surprising, perhaps, was that these same companies reported the vast majority of their capabilities and governance were based in North America and the European Union. Asia and non-EU countries accounted for less than 20% of local data capability strength.

Respondents, who also included Esteve, Bayer Health Care, Novartis, Janssen, Gilead, and Genentech, said they most valued big data partnerships with payers and data aggregators.

Click here to read more. (registration required)

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

Congress Crawls Out of 20th Century to Push Bi-partisan ‘Cures’ Legislation

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Just when we’d all decided Washington lawmakers couldn’t do much more than enjoy their own excellent health insurance coverage, tasty bean soup in the Senate cafeteria, and the best parking on Capitol Hill, it turns out they might actually unite to accomplish something pretty big after all.

It’s called the 21st Century Cures Act and its got a lot of device and drug makers excited. It’s been under development since April 2014. Amazingly, the version Congress released recently is almost 50% shorter than the earlier draft. In a city full of bureaucrats who write memos about memos, that’s a pretty incredible feat.

Fresh off a May 15 Congressional vote moving the law closer to passage, Mark Leahey, President and CEO of the Medical Device Manufacturers Association (MDMA), praised Subcommittee Chairman Joe Pitts and Ranking Member Gene Green for their bipartisan work “recognizing the importance of medical technology innovation in answering the pressing challenges facing America’s health care ecosystem.”

Joining AdvaMed, among others, Leahy applauded legislation he says “provides substantive proposals to improve the regulatory process, while addressing ongoing challenges in obtaining adequate reimbursement for the cures and treatments that patients need.”

Among a myriad of potential changes, the Act would clarify the standardization of eligibility information in clinicaltrials.gov, and spur the Department of Health and Human Services to forge ahead with additional public/private partnerships with grants to promote patient advocacy groups and research of disease causes, especially for rare diseases.

SixGroupsAccording to the folks at Hyman, Phelps and McNamara, the new version is broader in terms of Qualification of Drug Development Tools. For example, “it now addresses biomarkers, surrogate endpoints, and other drug development tools; the first discussion draft focused primarily on surrogate endpoints,” reports the firm’s Law Blog. “On the other hand, it is narrower because it does not affect devices. The section also removes many of the formal procedures and timelines from the first discussion draft and provides FDA with more discretion in the development of the program.”

There’s still a lot to dissect from the Act, and, while passage appears likely, some provisions could still be tweaked or cut entirely. But one this is clear: Congress is probably going to shock a lot of us by actually pulling together a relatively bi-partisan piece of legislation and placing it on President Obama’s desk before the end of the year.

Who’d have thought, right? Now, maybe these distinguished men and women can take a hard look at our nation’s infrastructure, tax code, and maybe a few dozen other issues that would also benefit from some good, old-fashioned bipartisan discourse.

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

Should FDA Get Tougher on IRBs?

Patrick Stone

Patrick Stone, President, TradeStoneQA

The FDA says IRB’s (Investigational Review Boards) are not required to collect a statement of investigator assurance from studies they preside over.

This is troubling. My first question would be how are IRB’s going to assure clinical investigators will abide by requisite 21 code of federal regulations (CFR) and the sponsor approved protocol? How will IRB’s ensure that the protocol they are approving is authorized by FDA for human clinical trials?

fancyFDAlogoClinicaltrials.gov is a great repository and can be a big help here, but only if it used by the IRB’s and updated in a timely manner. In my day as an FDA inspector [1998] we were trained that IRB’s are FDA’s eyes and ear’s because FDA is not going to get to very many clinical investigator audits. Fewer than one percent of clinical trials ongoing domestically are reviewed by the agency.

That’s why I’m a little worried. Why would FDA abandon a last line of defense for patient safety? I’m not sure why the agency takes this position, but luckily for patients, most IRB’s do hold clinical investigators accountable for all HHS requirements (FDA & OHRP) and even conduct quality audits for a small percentage of the clinical trials they preside over. If 21 CFR is the bare minimum requirement for compliance, wouldn’t additional IRB oversight be a big boost to compliance if FDA is not able to review a much higher percentage of the domestic ongoing clinical trials?

There’s another area of concern: A 2013 FDA guidance states that only sponsors and clinical Investigators need to keep track of financial disclosure documents. Financial disclosure should be reviewed by IRB’s especially institutional IRB’s that can easily verify if conflicts of interest exist for clinical investigators under their review.

But let’s save that topic for the next time!

Patrick Stone is the author of Bubble Gum Badge – An FDA His-Story. You can also follow him on Twitter.

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

FDA FastStats: CDRH Shows Significant Growth in Electronic Submissions; Deadline Looming for eMDR

No more paper. That’s what the FDA requires from the medical device community starting August 14, 2015 with regards to electronic medical device reporting (eMDR). With the draft guidance initially introduced in 2009, and the final rule released in 2014, medical device manufacturers have a little over three months to comply. In the infographic shown below, CDRH submissions overall have dramatically increased through the years. Back in 2006, only 1,575 records were submitted electronically by CDRH to FDA. At year end 2014, electronic submissions to CDRH had reached a record high of 812,443 and are expected to continue to rise going forward.

 

FDAeMDR

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

FDA’s Action Plan Demands Some Industry Action, Too

Patrick Stone

Patrick Stone, President, TradeStoneQA

“The following Pharmaceuticals FY 2015 Action Plan (the Action Plan), developed by the Office of Regulatory Affairs (ORA), the Center for Drug Evaluation and Research (CDER), and the Center for Veterinary Medicine (CVM), is intended to facilitate operational and program alignment as FDA transitions to distinct commodity-based and vertically-integrated regulatory programs with well-defined leads, coherent policy and strategy development, and well-designed and coordinated implementation.

That’s the FDA’s plain Jane version of its 2015 Action Plan. But let’s look at some interesting wrinkles not necessarily contained in the document.

The Pharmaceuticals Inspectorate will change the way FDA inspectors conducts audits and how many audits will be conducted in a years’ time. There are some interesting things to note here: First, the Center for Biologics (CBER) is noticeably not included in this reorganization effort. Second, district offices will not be at the helm when it comes to which drug firms get inspected and how compliance OAI & VAI cases are handled. Third, CDER will be assuming the lead role and Center compliance teams will be responsible for industry corrective action plans.

prescription drugsTraditionally, the district compliance team for the drug company took the lead role in compliance strategy and remediation. But now, the inspectors conducting drug audits will be dedicated and certified to conduct inspections. This will reduce errors and enhance the quality of inspections domestically and internationally. This will also increase the number of observations (483 notice of observations), warning letters, and consent decrees.

When a generalist inspector conducts a drug audit they may miss a system wide failure or process control deviation due to a lack of training. By contrast, when a professional team of inspectors with dedicated drug training for a drug firms system conduct an audit, those same compliance issues are not usually missed. This is a positive step in the right direction however building the new drug teams and training them accordingly will take years.

Quality by design (QbD) implementation is looming so this will also affect the training requirements from a system based approach to a QbD approach.

Don’t be caught off-guard by this new way of doing things. The FDA is making some changes here, and regulated firms need to make sure they understand them.

Patrick Stone is the author of Bubble Gum Badge – An FDA His-Story. You can also follow him on Twitter.

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

FDA Works to Clarify Device Data Collection Priorities

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

A new FDA guidance issued by the Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) offers some helpful detail for device firms uncertain if post-approval studies can replace premarket studies at the time of approval for premarket approval applications (PMAs).

The agency says there are some instances where it may consider it acceptable to collect certain data in a postmarket setting rather than premarket.

FDAlogoOne area is mature technologies. For example, a subcutaneous implantable cardioverter defibrillator (S-ICD) has the same basic elements of an ICD, which have been used for decades. Clinical and preclinical evaluations in the premarket setting for the subcutaneous ICD were tailored to collect data on the new aspects and to evaluate functionality of the device, while more detailed safety data is collected in a postmarket study.

Other situations include an urgent public health need, especially in a situation where postmarket testing would do a better job confirming the benefits of a device.

The guidance spells out several other examples where it may be appropriate, including:

  • Migration, an approach used when approval of Class III in vitro diagnostic devices previously approved, licensed, or cleared assay is shifted to another system for which FDA hasn’t evaluated assay performance, is suitable in cases when sufficient knowledge can be gleaned for the documentation of design controls, risk analyses, and prior performance studies on an already marketed system.
  • Confirmation of mitigation effectiveness for a known risk in a post-approval study.
  • Modifying warnings, contraindications, and/or precautions in approved labeling.
  • Approval for an intended population beyond what was fully evaluated in the pivotal trial, with a confirmatory post-approval study.
  • Assessment of long-term performance in a post-approval study.
  • Assessment of rare adverse events in a post-approval study.
  • Confirmation of bench data with clinical data collected in a post-approval study.
  • Where the performance of a particular device type is well-studied, documented, and understood
  • Where long-term outside the U.S. clinical performance data is available but deemed insufficient.
TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

FDA Plays Catch Up In Brave New World of Electronic Consent

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Informed consent (IC) is more than getting a quick signature from a clinical trial participant, the FDA gently reminds industry in a new guidance addressing increasingly complicated electronic IC (eIC) issues. Issued almost simultaneously with Apple’s new ResearchKit tool which promises faster, cheaper access to potential trial participants, and unimagined data streams to boot, the guidance comes at an important time for the clinical trial world.

Never accused of being early adopters of technology, clinical trial folks need to heed the FDA’s new guidance. Used properly, it can serve as something of a roadmap as everyone veers into previously unchartered territory.

First, understand the FDA’s expectations as laid out in the new guidance. It expects subjects to receive enough information to allow for an informed decision and an easy way to ask questions and receive jargon-free answers.

When using an eIC, FDA requires it to contain all elements of traditional IC, but also that any interactive eIC program be easy to navigate, including the means for the subject to stop and return to it later. Further, eIC tools must meet any subject’s physical limitations, e.g. poor vision or impaired motor skills. Perhaps most importantly, the eIC “must be presented in a manner that minimizes the possibility of coercion or undue influence regarding the subject’s decision to participate in a study.

FDAlogoFDA requires an investigator to obtain the informed consent. However, if the investigator delegates the responsibility, it is their obligation to hire a surrogate with demonstrable credentials. Nothing new there. But it gets a little more complicated when it comes to eIC. For example, consent can be handled remotely. However, when the consent process is not personally witnessed by study personnel, the eIC should include a method to ensure that the person giving consent is the person participating, or the subject’s legally authorized representative. The subject must also have the opportunity to ask questions and receive answers before actually signing electronically.

A subjects’ questions can be answered in a number of ways, including text message, phone calls, and videoconferencing. The data and communications must be secure. Subjects should also be told in advance how and when they will receive answers to questions and given information on how to contact an appropriate individual with questions about the investigation, the subjects’ rights and whom to contact in the event that a research-related injury occurs.

FDA also issues some eIC direction to IRBs. “A critical part” of an IRBs responsibility is to ensure that there is an adequate informed consent process in place that protects the rights and welfare of subjects participating in clinical investigations. Further, the agency recommends, but does not outright require, that an investigator discuss plans for using eIC with the IRB before finalizing development of the eIC to ensure that the IRB agrees that a particular format may be used for obtaining informed consent.

The FDA remains neutral when it comes to archiving documents. That said, the agency does weigh in on “cloud” and other remote storage solutions. Data privacy laws and regulations that apply to the remote site, in addition to those that apply to the research site itself, “may apply and should be considered.”

Finally, the agency reminds us that when one of its cheerful investigators is waiting in your lobby, he or she will be expecting access to records and reports made by the investigator including site-specific versions of eICs, materials submitted to IRBs for review and approval, all amendments to the site-specific eICs, and all subject-specific signed eICs. Any updates to the documentation must also be available for review.

Comments on the guidance are due May 8. When submitting your input, refer to docket no. FDA-2015-D-0390

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

Brookings Looks to Advance Medical Device Postmarket Surveillance System

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Patients and medical device innovators will benefit if the United States is able to launch a National Device Postmarket Surveillance System (MDS), says a new report by the Brookings Institution with input from a wide swath of public-private players including the Office of Surveillance and Biometrics Center for Devices and Radiological Health.

The Brookings paper, “Strengthening Patient Care: Building an Effective National Medical Device Surveillance System,” calls for an MDS that’s responsible for coordinating medical device postmarket evidence activities, then builds and facilitates access to a network of data partners. The report also stresses, however, that the MDS should not work in a vacuum. Instead, it should be built upon and coordinate with existing public and private sector programs to better leverage existing expertise and resources.

Brookings envisions a system that collaborates with other groups to support other high-priority evidence needs that may benefit from the same infrastructure, including product tracking and utilization, clinical quality improvement, and economic analysis of medical device-related care.

medicaldeviceThe Brookings Planning Board (PB) suggests the new MDS be implemented and managed by a wide array of stakeholders. But none of this is going to happen overnight. The PB envisions a seven-year rollout, with the first two years devoted to an incubator project tasked with developing a five-year MDS implementation plan.

Ideally, the incubator project would be initiated by the FDA. The report lays it out pretty clearly. “Without some initial seed funding and active FDA engagement, it will be difficult to assure the purpose and sustain the momentum necessary for other stakeholders to fully engage in the development of MDS.”

Finding funds won’t be easy, the report authors acknowledge. For example, the FDA does not currently have any specific appropriations dedicated to paying for the initiative. Congress enacted legislation in 2012 mandating the agency expand the Sentinel system to include medical devices. Unfortunately, folks on Capitol Hill didn’t come up with or identify other sources for the cash to fund it. The PB calls for “more explicit Congressional support” to support and fund the infrastructure required to emerge with a robust system of medical device surveillance in this country.

While Washington’s culture of gridlock isn’t exactly encouraging, maybe the prospect of safer medical devices developed in a climate that encourages innovation is the kind of thing a few of them can actually support on the same day. We’ll see.

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

FDA Gives MDDS World a Big Break

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Sometimes it’s nice to be told what the FDA isnt going to do. The agency issued a guidance last month that should give anyone building or working with a Medical Device Data System (MDDS) happy and relieved. Can you hear the collective sigh?

FDA defines MDDS as any hardware or software that transfers, stores, converts, and or/displays medical device data. To be considered MDDS, the product cannot modify either the data or its display. It also cannot, by itself, control the functions of a medical device. MDDS is not supposed to be used for active patient monitoring. FDA’s MDDS examples include:

  • software that stores patient data such as blood pressure readings for review at a later time;
  • software that converts digital data generated by a pulse oximeter into a format that can be printed; and
  • software that displays a previously stored electrocardiogram for a particular patient.

FDA logoThe February 9 guidance, building on a June 2014 draft document, advises manufactures, distributors and others involved that it “does not intend to enforce compliance with the regulatory controls that apply to MDDS, medical image storage devices, and medical image communications devices.” Industry should thank the FDA for acknowledging the low-risk nature of such devices. Further, the agency cited the “importance they play in advancing digital health.”

Specifically, the agency is giving out three free passes: MDDS previously subject to 21 CFR 880.6310, medical image storage devices previously subject to 21 CFR 892.2010, and medical image communications previously devices subject to 21 CFR 892.2020.

Comments, or applause, can be sent to the agency at www.regulations.gov. Cite document number 140021. The agency does point out, however, that comments may not be acted upon until the document is next revised or updated.

Stuck for a comment idea? Well, flowers are always nice. People love those big tins of caramel popcorn, too.

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare

FDA CDRH Enforcement: Agency Eases Up a Bit at Home, Looks Overseas

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Quality system surveillance inspections dropped about 3% in 2013, the FDA’s Center for Devices and Radiological Health (CDRH) says in its latest stats. It’s not sure why, exactly, but posits it’s due to an increase in inspections overseas. That drains away resources for domestic doings.

It’s worth noting that the overall number of inspectional observations dropped by 17 percent in FDA’s latest stats from 2013. FDA’s most frequent inspectional observations remained consistent, with Corrective and preventive action procedures (CAPA) leading the way, followed by complaint reviewing, receiving and evaluating. The trio was rounded out by problems with quality audits to assure quality systems are in compliance. Not much new there. Still, it’s important to know.

For the first time since 2009, the number of warning letters issued by CDRH dropped according to the agency’s most recent annual stats. Fewer than 5% of domestic firms and over 15% of foreign firms inspected received warning letters. That might sound good to US-based device makers, but as manufacturing moves more and more overseas, those higher stats are becoming their problem, too.

FDAlogoUntil we receive more recent numbers, we’ll have to look for anecdotal evidence suggesting any deviation in the FDA’s regulatory focus in 2014 or 2015. So far, it’s looking like business as usual.

Let’s take a quick look at some recent warning letters to better illustrate the point:

While FDA’s overseas inspections have tended to focus on India and China, CDRH hit Spanish-based DIMA, a manufacturer of slings and incontinence mesh products, with a warning letter for insufficient environmental controls and other good manufacturing practice (GMP) shortcomings. CDRH hit the form for not having change handling procedures that were up to the mark, and failure to demonstrate that a CAPA it opened ultimately did not require corrective actions.

Back in Tonawanda NY, CDRH’s January 23 warning letter to Praxair criticized the firm for not having clear definitions for what qualified as a reportable event. Further, the agency said the company did not require verification of validation of CAPAs. Praxair makes gas flow products that regulate oxygen flow.

Related:

FDA FastStats: A Look Back at 2013 Medical Device Warning Letters and Quality System Deficiencies

TwitterFacebookGoogle+LinkedInEmailPrintFriendlyShare