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Medical Device Complaint Management 2015 complaint definition fda

Medical Device Complaint Management 2015 HOME Agenda Venue Speaker Brochure register


When one of your products triggers a customer complaint, you respond pronto. You dot the i’s and cross the t’s. You think you’ve made all the right moves, but chances are …

… you haven’t.

Worse, you may have inadvertently exposed your company to sanctions. Penalty letters … design changes … new UDI-DI … correction/removal … new 510(k) … all are possible.

Regardless of where you base your operation — the U.S., the EU or Canada — the problems are the same. Your company quietly changes even one long-standing practice and presto, you find yourself facing a punishing sanction.

You need a system. You need a plan. You need:

Medical Device Complaint Management Building a Robust System to Meet Global Requirements

Mark your calendar for Boston in February, when FDAnews and Ombu Enterprises host an all-new two-day workshop that’ll transform your device company into a well-oiled complaint management machine.

You start with a hypothetical complaint, then trace it through the regulatory system. First come lectures, then interactive exercises — 11 of them over two days. You find yourself out of your chair and engaging with devicemakers like yourself — from the E.U., Canada and all across the U.S. — confronting and solving shared problems.

At the conclusion of each small-group exercise, you take a test. But not to worry — you can’t fail. Answers will be provided, plus proven solutions to take home and apply in your operation. We know of no other workshop providing such fine-grained level of interactivity, not to mention solutions you can put into effect — at once.

Your mentor is Dan O’Leary, a 30-year veteran of device quality compliance and five-star presenter. Mr. O’Leary is a master at working with devicemakers large and small to apply proven methods that build end-to-end complaint management systems.

Here’s just a taste of topics you’ll cover:

The role of Unique Device Identification (UDI) in complaints and adverse event reporting Regulatory reporting requirements in three major markets: U.S., EU, Canada Understanding why the complaint source (Facebook, Twitter, email, phone call) is not your chief concern — it’s how you handle the communication Proper use of corrective action in complaint management, including statistical analysis Developing a complaint classification system that links to the risk management file Analysis methods to determine impact of design changes on regulatory requirements Planning field actions and making regulatory ceazyckn. moncler black fur hooded jacket men's reports And much more Click here for the full two-day program schedule.

In your fast-changing world, facing multiple regulatory bodies with complex and ever-changing rules, an effective complaint management program is a must. Don’t let an inefficient, outmoded complaint management system bring you down – not when help is at hand. Sign up now.

Course Description

This workshop helps you understand the regulatory system by starting with a complaint and tracing it through the various regulations, including interactions with regulatory agencies.  Complaints are an unrecognized problem in a company’s marketed product. Depending on the nature of the complaint, it could lead to corrective action, design changes, new UDI-DI, correction & removal, or even a new 510(k).  Using past experience and interactive exercises, this workshop teaches attendees how to deal with complaints and their implications throughout the entire regulatory structure in the US, EU, and Canada.

When one of your medical devices triggers a complaint, you respond immediately. You dot each i and cross each t. You think you’ve taken every prescribed step.

But complaint management is ever changing.  Recently there’s been a big focus on customer complaints through a company’s social medium channels.  Should your focus be on the complaint itself or the channel it was submitted through?

And despite all your hard work and focus on managing complaints, you and your colleagues still receive a Warning Letter. What’s going wrong?

What you may not realize is that FDA scrutiny can probe every aspect of your operation — customer service, field servicing, sales, device reporting, CA&PA, design change, corrections and removals, and more.

You need a system wide solution — one that turns your entire operation into a well-oiled complaint-handling machine. If you aren’t sure how to pull it off … FDAnews has created a one-of-a-kind workshop to help.

Using a combination of lectures and interactive exercises that will get you out of your chair and, working in small groups, this workshop will guide you through how to assure you’re focusing on ALL the areas that the FDA looks to hunt and peek within.

Dan O’Leary — a 30-year veteran of device quality compliance — is a master at working with companies large and small to apply proven methods to build end-to-end complaint management systems.

Through a combination of presentations and small group exercises Dan leads attendees through their toughest problems. At the conclusion of each presentation and exercise a “test” will take place, answers will be provided and attendees will have proven solutions they can take back to their operations. No other workshop provides this level of interactivity and take-home solutions.

Register Today.

Course Binder Materials: Full slides from the PowerPoint presentations A copy of each interactive exercise worksheet as well as answer keys An annotated version of MDR sections regulation based on recent Warning Letters An Excel worksheet that helps analyze the FDA regulations. It has a series of questions that start with a complaint and follow the reporting and record keeping decisions to help understand the integrated requirements spread across different parts of the regulations. Reference documents: FDA guidance on Medical Device Reporting FDA draft guidance on Medical Device Reporting Comparison of MDR Rule Changes FDA guidance on Enhancements and Recalls Comparison Part 7 and Part 806 definitions FDA guidance document on 510(k) changes MEDDEV document on the Vigilance System Health Canada document on Medical Device Problem Reporting

your expert speaker

Dan O'Leary,

President at Ombu Enterprises, LLC


"[Dan is an] Excellent speaker. Great experience and examples. Interactive discussions in particularly were very helpful.” — Brian Ray, Senior Manager Risk Management, Welch Allyn

"Dan is an excellent speaker who folds a lot of knowledge and experience.” — Joaquin Bautista, Quality Specialist, Colgate-Palmolive Co.


Who will benefit?

Quality Managers Regulatory Affairs Managers Engineering Managers Quality Engineers Design Engineers Project Managers involved in design and development Specialists assigned to complaints, corrective actions, or medical device reporting Recall coordinators Medical staff evaluating risk, safety or effectiveness General/corporate counsel

This conference has been pre-approved by RAPS as eligible for up to 12 credits towards a participant's RAC recertification.

Team Discounts

Significant tuition discounts are available for teams of two or more from the same company. You must register at the same time and provide a single payment to take advantage of the discount. Call +1 (703) 538-7600 for details.

    Agenda  |  Venue  |  Speaker  |  Register

300 N. Washington St., Suite 200, Falls Church, VA 22046, USA. Phone (703) 538-7600 – Fax (703) 538-7676 – Toll free (888) 838-5578


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moncler baby snowsuit uk Recalls, Remedial Actions, and Other Field Corrections Posted by mddiadmin on December 1, 2004 Share

Originally Published MDDI December 2004

Regulatory Outlook

Recalls, Remedial Actions, and Other Field Corrections

Even with the best preparation, something can go wrong. An effective strategy is essential to surviving a recall.

Larry R. Pilot McKenna Long & Aldridge LLP

Larry R. Pilot

Among the products subject to litigation for alleged damages are those regulated by FDA. From one perspective, FDA regulation can provide a defense against the possibility of recovery for damages incurred. However, FDA involvement can also become a source of information, facts, and liability theories that can increase a product's exposure to liability.

Before the Medical Device Amendments of 1976, FDA had no authority to recognize or mandate a recall or remedial action for any product subject to the Federal Food, Drug, and Cosmetic Act (FD&C Act). However, FDA did have an enforcement policy to define and classify the nature of a recall.

This policy, which appears in 21 CFR Part 7, has been in effect since the 1970s. 1 Its aim was to develop criteria for what constitutes a recall. The policy also defines the level of seriousness of a recall in relation to health risk. Because the point of a recall is for the manufacturer to voluntarily correct alleged FD&C Act violations, FDA created a way to order a recall if a manufacturer will not take remedial action.

Terms and Definitions Although the dictionary definition for the term recall has various applications, the term as defined by FDA has regulatory implications that are not considered by the dictionary definition. FDA defines recall, correction, and market withdrawal as follows:

• Recall means a firm's removal or correction of a marketed product that FDA considers to be in violation of the laws it administers and against which the agency would initiate legal action, e.g., seizure. Recall does not include a market withdrawal or a stock recovery. 2 • Correction means repair, modification, adjustment, relabeling, destruction, or inspection (including patient monitoring) of a product without its physical removal to some other location. 3 • Market withdrawal means a firm's removal or correction of a distributed product that involves a minor violation that would not be subject to legal action by FDA or that involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs, etc. 4

The essence of FDA's recall definition is the activity that FDA “… considers to be in violation of the laws that it administers and against which the agency would initiate legal action…”

Whether correction of the alleged violation is addressed by physical removal or other means, FDA's identification of the activity as a recall signifies the agency's belief that a violation of the FD&C Act exists. A device may be withdrawn from the market, or it may qualify for remedial activity without violating the FD&C Act.

Consequently, individuals responsible for field activities must avoid admitting a violation. Interpretations of the requirements of the law and regulation may differ as to whether a violation exists. Regardless, FDA applies its definition of recall to determine the nature of the action. The ultimate resolution of any disagreement about whether there is a violation is a function of the judicial process.

In some cases, FDA believes that its evidence does not provide support for a voluntary remedial action. The agency may then determine that a violation represents “a reasonable probability” of “serious adverse consequences or death.” In these cases, FDA may formally request initiation of a recall. If the recipient of the request is unwilling to act, FDA (through the Department of Justice) may seize the devices or enjoin their distribution. Likewise, those responsible for causing the violation can be prosecuted. In either event, the burden is on FDA to prove its position in federal court.

Recall Order Before the 1990 amendments, infant formula was the only product under the authority of the FD&C Act to be subject to FDA recall. The 1990 amendments authorized FDA to order a recall under certain conditions. Where FDA finds “…that there is a reasonable probability that a device intended for human use would cause serious adverse health consequences or death…” FDA must issue an order. This order, which is expected to state the grounds supporting the order, also directs that distribution cease, and it requires the manufacturer to notify affected parties.

FDA must also offer a formal hearing to those parties who are subject to the order. The medical device recall authority regulation addresses this authority. 5 Because the explicit language in the FD&C Act limits application of the potential for an order, this regulation provides a different definition for the term recall, and it provides an explicit definition of removal. These definitions are as follows:

• Recall means the correction or removal of a device for human use where FDA finds that there is a reasonable probability that the device would cause serious adverse health consequences or death. • Removal means the physical removal of a device from its point of use to some other location for repair, modification, adjustment, relabeling, destruction, or inspection.

To order a recall, FDA must first provide the appropriate person with the opportunity to consult with FDA. After consultation, FDA has the burden to find “…that there is a reasonable probability that a device intended for human use would cause serious, adverse health consequences or death…” to support its order. A recall order specifies the actions that are to be taken by the named person. The order also includes the following immediate requirements: cease distribution, notify health professionals and user facilities, and instruct the user and user facilities to cease use of the device. In addition, the following information is included in the order:

• The requirements of the order that relates to the cessation of distribution and notification of health professionals and device user facilities. • Pertinent descriptive information that would enable accurate and immediate identification of the device subject to the order, including the brand name of the device; the common name, classification name, or usual name of the device; the model, catalog, or product code numbers of the device; and the manufacturing lot numbers or serial numbers of the device or other identification numbers. • A statement summarizing the grounds for FDA's finding that there is a reasonable probability that the device would cause serious, adverse health consequences or death.

Other information can also be included in the order, but the manufacturer may request a hearing to appeal the order. Alternatively, manufacturers may submit a written request to FDA that the order be modified, vacated, or amended. If an appeal is pursued, FDA issues its response within 15 working days of completion of its review (i.e., hearing or receipt of written request).

FDA's modified or amended order is a final agency action for which the appropriate person may seek judicial relief. Since the 1997 effective date, at least one order has been issued. Voluntary compliance with FDA enforcement policy on recalls appears to be an adequate method for addressing remedial actions for alleged FD&C Act violations.

Corrections and Removals The 1990 amendments authorized FDA to require a manufacturer to report promptly to FDA any device correction or removal taken to reduce a health risk posed by the device. Manufacturers must also report the action if it is taken to remedy an FD&C Act violation that may present a health risk.

The reports of corrections and removals regulation became effective March 27, 2000. 6 It differs from the long-standing FDA policy relating to voluntary recalls and market withdrawals and from FDA's policy relating to the mandatory recall order process. Unlike these regulations, the corrections and removals regulation imposes a direct burden on device manufacturers. Simply put, manufacturers must make a judgment call relating to what the regulation expresses as “risk to health.” If the anticipated removal or correction is taken to reduce risk, a report must be submitted to FDA within 10 days of initiating the removal or correction.

The legal requirement to notify FDA of corrections and removals imposes an unusual and challenging burden for device manufacturers. Failure to notify FDA of this type of recall is a violation of the FD&C Act. There has been no litigation to enforce a penalty against those who have failed to comply with the corrections and removals regulation. However, the potential is realistic, depending on the regulatory environment. Individuals responsible for reviewing complaints, filing medical device reports, and participating in the review of remedial actions relating to a device must also consider notifying FDA as part of their responsibility.

The 1990 congressional mandate is not explained well, but it is clear that a manufacturer's decision to report must be based on “risk to health.” FDA defines the phrase as follows:

• A reasonable probability that use of, or exposure to, the product will cause serious adverse health consequences or death; or • That use of, or exposure to, the product may cause temporary or medically reversible adverse health consequences, or an outcome where the probability of serious adverse health consequences is remote.

When a manufacturer contemplates remedial action for a device in commercial distribution, this risk to health definition must be considered when deciding whether to report the action to FDA. This decision-making process should also involve reviewing definitions from other FDA regulations (e.g., medical device reporting (MDR), enforcement policy, medical device recall authority, etc.). Manufacturers should develop a procedure for remedial actions. Because of the implications of such actions, it is essential to include the opinion of a medical advisor as to whether to file a corrections and removals report.

Another important factor to review in a health risk evaluation is the regulation's reference to violation. Something could go wrong with a device that is properly designed, manufactured, and used. However, the complicated structure of statute and regulation makes the determination of a violation difficult. FDA and the manufacturer may disagree as to whether a violation has occurred. Ultimately, it is up to FDA to prove that a violation exists. Consequently, both FDA and the manufacturer must be cognizant of due process and the quality of the evidence.

Manufacturers must apply and document their remedial-action approach. It is important to keep in mind that FDA may challenge the method chosen. One approach is to evaluate the performance of devices as part of a complaint-handling process and as part of the firm's application of its MDR procedure. If application of a documented procedure suggests the need for correction or removal as a remedial action, then an assessment of health risk is indicated. This is a difficult task. It is also difficult to determine whether the cause of an identified health risk is related to an FD&C Act violation.

Likewise, FDA must understand the difficulty associated with the decision-making process. The corrections and removals regulation and its preamble provide no explicit guidance. Consequently, when evaluating a manufacturer's judgment, FDA must apply discretion and consider the type and variety of devices and the conditions under which the device is used. FDA should cooperate with manufacturers and agree on an approach appropriate for the nature of the risk.

When judgment is required, no provision in a regulation can function as a surrogate. There is no motivation for manufacturers to market unsafe or ineffective medical devices. The potential for product liability lawsuits because of injury to users is a potent ancillary to the regulatory function of FDA.

The concept of risk assessment exists as part of the quality system regulation, but the device industry should also participate in the process of developing and implementing a fair and balanced approach to risk assessment in relation to product benefit.

In the meantime, device manufacturers should also implement procedures to identify health risk. Manufacturers should recognize, however, that FDA might challenge the outcome of the application of a company's risk-assessment procedure. If the challenge occurs as part of a routine FDA inspection or as an initiative by CDRH, the best possible defense to a challenge will be the company's documentation indicating compliance with a comprehensive procedure.

Managing Field Corrective Actions Regardless of the reason for remedial field corrections, a conscientious manufacturer should aim to correct the problem to maintain customer loyalty and satisfaction. Once FDA determines that a manufacturer has voluntarily corrected a violation, the agency has explicit procedures it expects the manufacturer to follow. These procedures are described in the recall regulation in 21 CFR Part 7, Subpart C, as well as in FDA guidance documents.

FDA reviews information collected from the manufacturer. A health-hazard evaluation is conducted to determine a recall classification. Possible recall classifications include:

• Class I: There is a reasonable probability that the use of, or exposure to, a violative product will cause serious adverse health consequences or death. • Class II: Use of, or exposure to, a violative product may cause temporary or medically reversible adverse health consequences, or the probability of serious adverse health consequences is remote. • Class III: Use of, or exposure to, a violative product is not likely to cause adverse health consequences.

The classification determines FDA's expectations of the manufacturer's recall strategy. The strategy varies depending on the health risk and device type. The recall of a life-supporting or life-sustaining device may require direct contact with the user and possible assistance, including publicity, from FDA.

FDA's recalls regulations and a guidance for industry released in November 2003 provide useful information and advice for developing a procedure. FDA also looks at the effectiveness of a recall. The regulations and the guidance document address how FDA ensures effective completion of a recall.

Although there is a benefit to the prompt and effective completion of a remedial action, completion also indicates the eventual disclosure of FDA documents under the Freedom of Information Act. The quality of the manufacturer's performance will determine whether the content of such documents encourages or discourages product liability complaints.


In a world of perfect device performance, there would never be a need for a remedial action. This is unrealistic. Therefore, in the quest for device perfection, it is important to recognize that even with the best design and foresight as to a product's use, something could go wrong. If something does go wrong, the procedure that one never expected to use should represent the preparation that enables a manufacturer to maintain user confidence and loyalty and avoid needless litigation.

References 1. Code of Federal Regulations, 21 CFR Part 7. 2. 21 CFR Part 7, Section 3 (g). 3. 21 CFR Part 7, Section 3 (h). 4. 21 CFR Part 7, Section 3 (j). 5. 21 CFR Part 810. 6. 21 CFR Part 806.

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19 July 2011 Registry Studies: Why and How

There is only one difference between registry studies and clinical studies: registry studies are observational and clinical studies are investigational. (When clinical studies are randomized they are called randomized clinical studies or RCTs.) To put it another way, in a registry study we tell the physician to treat the condition however they want—as sponsors, we are passive observers; in a clinical study we instruct the investigator to treat the condition in a certain manner—we are active researchers.

There is another, inevitable, feature of registry studies that I want to point out. The words "effectiveness" and "efficacy" are often misused, even by FDA. Effectiveness refers to how well a device performs as intended in the general population of patients and the general chaos of clinical practice. Effectiveness is measured in registry studies. Efficacy refers to how well a device performs in a setting of carefully selected patients and a carefully controlled protocol. Efficacy is measured in clinical studies.


Why do a registry study? [1] Reimbursement data One common reason for doing a registry study is to obtain data for reimbursement purposes. While CMS prefers comparative effectiveness data obtained from randomized clinical trials, such studies aren't always possible. 1. Definition of Comparative Effectiveness. There may not be a direct comparator for your new technology: the comparators might be an office procedure versus a surgical procedure or a device versus a drug. Imagine the complexities of comparing a device that emits a magnetic field intended to lower the viral load of patients with AIDS or hepatitis C to a multi-drug regimen. Or co-pay policies may be different for the comparators. Martin et. al. described an issue where a new (possibly more effective) drug costing $2000 per month was to be compared to an older drug being used off-label and costing $50 per month. There was concern that patients assigned to receive the expensive drug would drop out of the study. 2. Martin, et. al. In such a case, the sponsor would pick up the copay for every subject, no matter what their third-party coverage might be, in order to level the playing field.

[ 2] Post-approval effectiveness publications Before adopting your technology most clinicians will ask about its effectiveness in the real world. Registry studies are ideal for obtaining effectiveness data. By allowing wide patient selection criteria you will include patients with multiple confounding complications, wide age ranges, various socioeconomic backgrounds, and differing healthcare attitudes. Learning how your technology behaves in these complex scenarios can provide valuable information to clinicians and important data for publications.

[3] Section 522 In certain circumstances FDA may require a post-approval study under Section 522 of the Food, Drug, and Cosmetic Act. The so-called Section 522 Postmarket Surveillance authority is limited to Class II or Class III devices the failure of which might lead to serious adverse health consequences, devices implanted for more than one year, life-sustaining or life-supporting devices used outside a device user facility, or devices used in pediatric populations. 3. Section 522. Registry studies are an ideal way to collect the broad surveillance data required.

[4] Off-label uses Devices aren't always used the way we think they will be or in the populations we anticipate. In registry studies we—as sponsors—are not dictating how our device will be used, so there is always the possibility it will be used off label. Off-label use in a registry study is not a protocol violation since we don't specify in the protocol how to use the device in the first place. A review of how our device is actually used in real-world practice can provide valuable marketing information, hypothesis development for future studies, and indications for use development for future regulatory submissions.


How to do a registry study Implementing a registry study is not much different than implementing a clinical study. All the basic elements of design, planning, and project management are present. There is a lack of consensus standards for registry studies so it is difficult to find guidance on how to do them. Your primary resource for information will be "Registries for Evaluating Patient Outcomes: A User's Guide, Second Edition" from the Agency for Healthcare Research and Quality. 4. Registries.

[1] Planning In the planning phase, identify your stakeholders, the scope of data required, define the core data set (what do you need to know?), identify the patient outcomes or endpoints, define the target population (i.e. inclusion and exclusion criteria), and most importantly, get your funding. Funding may come from top management, venture capital firms, government grants, private grants, or other resources, but in the end we are all accountable to someone. Next you'll set up the registry team, determine if safety monitoring boards, IRBs, or other committees are necessary, and finally plan an exit strategy so you'll know when the study is completed.

[2] Registry design In the design phase, the details of the registry study are worked out and a protocol is written. There are only a few options for study design:

a) Cohort designs follow over time a group of people who possess a characteristic to see if they develop a particular endpoint or outcome. 5. Registries, p38.

b) In case-control designs you gather 'cases' of patients who have a particular outcome or who have had a particular adverse event and 'controls' who have not, and then you look backwards to see what proportion had an exposure or characteristic of interest. For example, in the evaluation of re-stenosis after coronary angioplasty in patients with end-stage renal disease, investigators found both cases and controls from an existing PTCA registry. Alternatively, cases could come from the PTCA registry and controls from outside the registry (say, Medicare data). 5. Registries, p38 and p46.

For example, in 2004 Cordis began a registry designed to assess stenting outcomes in relation to the outcomes of their SAPPHIRE trial, which was used as the historic comparison group. The research question was to see if non-academic physicians would achieve the same level of success as the academic investigators used in the clinical study. The registry was conducted because of concerns by FDA and the Centers for Medicare and Medicaid Services (CMS), and involved 74 sites and 1493 patients. The large number of sites and subjects are characteristic of registry studies. 5. Registries, p38.

c) A case-cohort design is a statistical variant of a case-control study. Controls are sampled from a list of people, with each person having an equal probability of being sampled. 5. Registries, p38.

Help with Registry Studies

CDG is pleased to offer a five-hour workshop on designing and implementing registry studies for medical devices. Designed and recorded by Dr. Nancy J Stark, the workshop is a focused presentation of the AHRQ User Guide, adapted to medical device registries. You can find more information on our website. Scroll down to Registry Studies for Medical Devices.

If you're short on human resources and need to outsource the planning and implementation of a device registry study, please phone or email us at 773-489-5721 or . Dr. Stark will be happy to discuss a proposal.

[3] Selecting subjects and comparison groups The target population is all the patients with a common disease or condition or a common exposure. For example, the target population might be all people with cataracts, all women with urinary incontinence, or all people who have been exposed to radiation for cancer treatment. Then broad inclusion/exclusion criteria are used to select a representative population of patients. One common feature of registries is that they have few inclusion and exclusion criteria, thus enhancing their applicability to broader populations.

Selecting comparison groups is more critical in observational studies than in clinical studies, because subjects have a choice as to which intervention they receive. The sickest patients may choose your technology, while less-ill patients may choose the comparator. The result will be an unfair imbalance in adverse events for the new technology. Key demographic factors—such as age, lifestyle, and disease advancement—are collected and statistically applied to help achieve equipoise.

Comparison groups may be "internal" (data collected simultaneously), "external" (data were collected outside of the registry, such as Medicare data), or "historical" (data collected under the registry protocol but not simultaneously). Comparison groups are essential when you want to distinguish between alternative procedures, assess the magnitude of differences, or determine the strength of associations between groups.

Registries do not need comparison groups when the purpose is to characterize the "natural history" of an intervention.

[4] What data should be collected? Registry enthusiasts have their own language for many of the concepts we are already familiar with from RCTs. For example, they talk about "domains" of data, and by that they mean data should be collected from the personal domain (patient demographics, medical history, health status, and patient identifiers), the exposure domain (patient's experience with the technology or device), and the outcomes domain (primary endpoints, secondary endpoints, adverse events, and technology deficiencies.) In addition, you should collect information about potential confounders (say a drug being taken to treat the same condition as the study device). The collected data should relate directly to the purpose of the registry.

"Data elements" refers to the exact data that will be collected. Currently there are few, if any, broadly accepted sets of standard data elements for most disease areas, making it difficult to use external data as a source of comparison data. Look to the specialty societies to see if they have created clinical data standards that you can use as a guide for selecting data for collection. For example, the American College of Cardiology has created clinical data standards for acute coronary syndromes, heart failure, and atrial fibrillation. 5. Registries, p53. Whenever possible, tie your data elements to established terminology, such as Current Procedural Terminology (CPT) codes, International Classification of Disease (ICD-10), or events related to device deficiencies. 6. ISO 19218-1.

[5] Data Sources for Registries Depending on the data sources required, registries may utilize certain personal identifiers for patients to locate the specific patients and link the data. For example, Social Security numbers (SSN), as well as a combination of other personal identifiers, can be utilized to identify individuals in the National Death Index (NDI). What peaks my interest is that data may come from many different sources: outpatient clinic records, inpatient hospital records, laboratory records, billing records, and even payer claims data! Data may come from medical chart abstraction, electronic medical records, institutional or organizational databases, administrative databases, death and birth records, census databases, or existing registry databases. For example, if you are developing a thermoebolization technology for treating liver cancer, you may want to access data from the Registry of Liver Diseases.

[6] Ethics, Data Ownership, and Privacy The principles of ethics, data ownership and privacy are the same for registry studies as they are for clinical studies. You need IRB approval to conduct the study, HIPAA waiver to access patient medical records, a financial agreement with the institution regarding payments, data ownership and publication rights, and assurances of patient privacy.

Consider the case study of the National Oncologic PET Registry, a registry developed to collect data about PET scans in cancer management with the goal of obtaining expanded CMS coverage for PET scans. The registry was to be conducted at hundreds of hospitals and free-standing PET facilities. The sponsor's believed the registry was not subject to IRB approval because it was being "conducted by or subject to the approval of Department or Agency heads" for the purpose of evaluating a "public benefits or services program." CMS agreed. One week before starting operation the Office of Human Research Protections (OHRP) issued a letter of disagreement. The study was put on hold while the sponsors contemplated the difficulty of obtaining approval from hundreds of IRBs. Ultimately OHRP conceded that only the registry was engaged in research and study needed to be approved by only a single IRB. 5. Registries, p84.

[7] Recruitment Recruitment of sites becomes a major issue in studies the breadth of registries. Sites must be paid fair-market value for their time and must see a benefit to their operations if they are to join and actively participate in a registry. This is especially true if the registry study is to include community physicians or high-volume specialty centers, as well as academic centers. Community physicians are more likely to participate if the registry is viewed as a scientific endeavor, is endorsed by leading organizations, led by a respected opinion-leader, provides useful self-assessment data to the physician, or helps meet other physician needs such as maintenance of certification, credentialing, or pay-for-performance programs.

Patient recruitment presents the same challenges as clinical studies. The best success comes from recruitment by the patient's own physician. It also helps to communicate that registry participation may help improve care for future patients, to provide written materials in language easily understood by the lay public, keep survey forms short and simple, and provide incentives such as newsletters, reports, and modest monetary compensation.

[8] Data collection and quality assurance Three sets of documents, together, form the system for data collection. The first is the case report forms, be they paper or electronic. These are the forms whereby data is gathered in the field, entered into coded fields, and transmitted to a data management center. The second is a data dictionary which contains a detailed description of each variable used in the registry. For example, the question may be: "Do you smoke?" And smoking may be defined has having smoked tobacco within the last year. The third is the set of data validation rules. These are logical checks on data entered to look for inconsistencies such as males taking birth control pills.

A data management manual should be developed to define how missing data will be handled, how invalid entries will be handled, how data will be cleaned, and what level of error will be accepted. The manual should describe how data will be tracked and coded, how query reports will be generated and resolved, and how it will be stored and secured. Finally, the data management manual should describe a quality assurance system for data entry and registry procedures.

[9] Adverse event reporting For device and device procedure registries, adverse event detection, collection, and reporting is the same as adverse event reporting for any other post-approval setting. It begins with the "becoming aware" principle; i.e. the clock for reporting adverse events starts at the moment the investigator becomes aware of symptoms or events reported by the patient or signs such as out-of-range laboratory results reported by a lab, or from the moment the manufacturer learns of an event from an investigator.

Investigators are responsible to report serious injuries to manufacturers within 10 days and to FDA within 10 days if the manufacturer is not known. Investigators are responsible to report deaths to both the manufacturer and FDA within 10 days. 7. 21 CFR 803. Interestingly, if an adverse event occurs with a comparator device the investigator must report the event to the comparator's manufacturer. Manufacturers have 30 days to report deaths, serious injuries and malfunctions to FDA, and 5 days to report events that require remedial action to prevent an unreasonable risk of substantial harm to the public health. Events are logged into the Manufacturer and User Facility Device Experience Database (MAUDE).

[10] Analysis and Interpretation Statistical analysis of registry data is no different than statistical analysis of clinical data. There are a couple of points that deserve mentioning, though. First, you'll need to determine how closely the actual study population represents the target population. Second, there should exist a statistical analysis plan for how the data are to be analyzed and interpreted. And third, there should exist a plan for how to handle missing data.

Conclusion Don't be misled, registry studies are not cheap, second-rate clinical studies. They are easily as complex and costly than the exalted RCT. What they are is different. They are observational studies that asses a technology's ability to achieve its intended use in the real world. They are used when alternative technologies don't exist, are outdated, or perhaps unethical.

References 1. Draft definition, prioritization Criteria, and Strategic Framework for Public Comment. 2. Identifying and Eliminating the Roadblocks to Comparative-Effectiveness Research, Martin, New England Journal of Medicine, June 2, 2010. 3. Food, Drug, and Cosmetic Act, Section 522 Postmarket Surveillance. 4. Registries for Evaluating Patient Outcomes: A User's Guide, Second Edition. Agency for Healthcare Research and Quality, 2010. 5. Registries for Evaluating Patient Outcomes: A User's Guide, Draft. Agency for Healthcare Research and Quality, 2006. 6. ISO/DTS 19218-1 Medical devices—Hierarchical coding for adverse events—Event type codes (2010). 7. 21 CFR 803 Medical Device Reporting.

Best Regards, Nancy J Stark, PhD President, Clinical Device Group Inc

Posted at 07:33 PM in Clinical Trials , CMS , FDA , Registry Studies , Reimbursement | Permalink


Informative article. Just a note: observational studies are not necessarily registry studies, and registry studies are still considered clinical studies, they are just not interventional in nature.

Posted by: David M | 30 August 2012 at 11:09 AM

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