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Gliklich RE, Dreyer NA, editors. Registries for Evaluating Patient Outcomes: A User's Guide. 2nd edition. Rockville (MD): Agency for Healthcare Research and Quality (US); 2010 Sep.

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Registries for Evaluating Patient Outcomes: A User's Guide. 2nd edition.

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Chapter 2Planning a Registry

Introduction

There is tremendous variability in size, scope, and resource requirements for registries. Registries may be large or small in their numbers of patients or participating sites. They may target rare or common conditions and exposures. They may require the collection of limited or extensive amounts of data, operate for short or long periods of time, and be funded generously or operate with limited financial support. In addition, the scope and focus of a registry may be adapted over time to reflect updated information, to reach broader or different populations, to assimilate additional data, to focus on or expand to different geographical regions, or to address new research questions. While this degree of flexibility confers enormous potential, registries require good planning in order to be successful.

When planning a registry, it is desirable to follow these initial steps: (1) articulate the purpose of the registry; (2) determine if a registry is an appropriate means to achieve the purpose; (3) identify key stakeholders; and (4) assess the feasibility of a registry.

Once a decision is made to proceed, the next considerations in planning are to (5) build a registry team; (6) establish a governance and oversight plan; (7) define the scope and rigor needed; (8) define the dataset, patient outcomes, and target population; (9) develop a study plan or protocol; and (10) develop a project plan. Registry planners should also (11) determine what will happen when the registry ends. Of course, the planning for a registry is often not a linear process. Many of the steps described in this chapter occur in parallel.

The Guidelines for Good Pharmacoepidemiology Practice from the International Society of Pharmacoepidemiology is a useful resource for registry planners, as are the STROBE (Strengthening The Reporting of Observational Studies in Epidemiology) guidelines for reporting observational studies.1,2 The Updated Guidelines for Evaluating Public Health Surveillance Systems may also be useful to planners, especially the appendixes, which provide various checklists.3 A Guide to the Project Management Body of Knowledge (PMBOK® Guide) may also be a useful resource to registry planners.4

Steps in Planning a Registry

Articulate the Purpose

One of the first steps in planning a registry is articulating the purpose. Having a clearly defined goal and/or purpose and supporting rationale makes it easier to evaluate whether a registry is the right approach for capturing the information of interest.5,6 In addition, a clearly defined purpose helps clarify the need for certain data. Conversely, having a clear sense of how the data may be used will help refine the stated purpose. Attempts to be all inclusive increase the likelihood of including data or procedures that add costs but not value, resulting in overly burdensome data collection that can reduce quality and erode compliance.

A registry may have a singular purpose, or it may serve several purposes.7 In either case, the overall purpose should be translated into specific objectives or questions to be addressed through the registry. This process needs to take into account the interests of those collaborating in the registry and the key audiences to be reached.8 Clear objectives are essential to define the structure and process of data collection and to ensure that the registry effectively addresses the important questions through the appropriate outcomes analyses. Specific objectives also help the registry to avoid collecting large amounts of data of limited value. The time and resources needed to collect and process data from a registry can be substantial.9 The identification of a core dataset is essential. The benefits of any data element included in the registry must outweigh the costs of including it.

Registry planners can begin to establish specific objectives by considering what key questions the registry needs to answer. Critical consideration needs to be given to defining the key questions in order to evaluate how best to proceed, as these questions will help to establish the type of registry (e.g., single focus or comparative), the data elements to be captured, and the types of analysis to be undertaken. Examples of key, or driving, questions are listed below:

  • What is the natural course of a disease, and how does geographic location affect the course?
  • Does a treatment lead to long-term benefits or harm, including delayed complications?
  • How is disease progression affected by available therapies?
  • What are significant predictors of poor outcomes?
  • What is the safety profile of a specific therapy?
  • Is a specific product or therapy teratogenic?
  • How do clinical practices vary, and what are the best predictors of treatment practices?
  • Are there disparities in the delivery and/or outcomes of care?
  • What characteristics or practices enhance compliance and adherence?
  • Do quality improvement programs affect patient outcomes, and, if so, how?
  • What process and outcomes metrics should be incorporated to track quality of patient care?
  • Should a particular procedure or product be a covered benefit in a particular population?
  • Was an intervention program or risk-management activity successful?
  • What are the resources used/economic parameters of actual use in typical patients?

Three of the case examples in this chapter provide examples of how key questions have shaped registries. (See Case Examples 1, 2, and 3.)

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Case Example 1

Using Registries To Understand Rare Diseases. Rare diseases pose special research challenges. The small number of affected patients often results in limited clinical experience within individual centers. Therefore, the clinical description of rare diseases (more...)

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Case Example 2

Creating a Registry To Fulfill Multiple Purposes and Using a Publications Committee To Review Data Requests. Over the past 20 years, there have been significant changes in the treatment of acute myocardial infarction (AMI) patients. Evidence from large (more...)

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Case Example 3

Using a Registry To Track Emerging Infectious Diseases. H5N1 is a major concern for global public health. Among the cases worldwide that have been confirmed by the World Health Organization, the virus has exhibited a mortality rate of almost 60 percent (more...)

Determine if a Registry Is an Appropriate Means To Achieve the Purpose

Two key questions to consider are whether a registry (or other study) is needed to address the purpose and, if the answer is yes, whether a registry is an appropriate means of accomplishing the scientific objectives. Every registry developer should consider early in the planning process:

  • Do these data already exist?
  • If so, are they of sufficient quality to answer the research question?
  • Are they accessible, or does an entirely new data collection effort need to be initiated?

For example, could the necessary data be extracted from electronic medical records or administrative health insurance claims data? In such cases, registries might avoid re-collecting data that have already been collected elsewhere and are accessible. Thought should be given to adapting the registry (based on extant data) and/or linking to other relevant data sources (including “piggybacking” onto other registries). When the required data have not been sufficiently collected or are not accessible for the desired purpose, it is appropriate to consider creating a new registry.

The next step is to consider whether the purpose would be best met by a clinical trial or a registry, and to consider that decision in the context of the state of current knowledge, gaps in evidence, how broad the target population of interest is, how complex the current treatment patterns are, how long an observational period would be needed to achieve the objective, the scope and variety of treatments used, the approximate amount of funding available to address these objectives, and the likelihood that a clinical trial could be conducted for the population of interest in a suitable timeframe. While clinical trials are extremely useful tools for studying treatment effectiveness and safety in narrowly focused populations where patients have high adherence to treatment protocols, clinical trials are quite rigid by design; are not suited to adaptation over time; are relatively expensive; and, by definition, cannot measure events under conditions of usual practice. If it appears that a more comprehensive, flexible research tool is needed, then a registry should be considered.10,11 A careful evaluation of the possibilities for data collection and registry design, the degree of certainty required, and the timeframe in which this certainty is expected can help in selecting an appropriate study design.

It is important to note that, historically, there has been a lack of consensus standards for conducting and reporting methods and results for registries. Therefore, registries have tended to be more variable in implementation and have been more difficult to assess for quality than randomized controlled trials. Advances in epidemiological and biostatistical methods have broadened the scope of questions that can be addressed through observational studies such as registries. Stratification, propensity score matching, and risk adjustment are increasingly useful approaches for addressing confounding issues and for creating comparably homogeneous subgroups for analysis within registry datasets, and advances in bias analysis are being used to help interpret results from observational studies such as registries.12,13,14 (See Chapters 3 and 13.) These techniques may allow registries to be used to support investigations of comparative safety and effectiveness. Following good registry practices, as described in this user’s guide, can strengthen scientific rigor. (See Chapters 10 and 14.)

Identify Key Stakeholders

As a means to identifying potential stakeholders, it is important to consider to whom the research questions matter. It is useful to identify these stakeholders at an early stage of the registry planning process, as they may have important input into the type and scope of data to be collected, they may ultimately be users of the data, and/or they may have a key role in disseminating the results of the registry.

One or more parties could be considered stakeholders of the registry. These parties could be as specific as a regulatory agency that will be monitoring postmarketing studies or as broad as the general population, or simply those patients with the conditions of interest. Often, a stakeholder’s input directly influences whether development of a registry can proceed, and it can have a strong influence on how a registry is conducted. A regulatory agency looking for management of a therapeutic with a known toxicity profile may require a different registry design than a manufacturer with general questions about how a product is being used.

Typically, there are primary and secondary stakeholders for any registry. A primary stakeholder is usually responsible for creating and funding the registry. The party that requires the data, such as a regulatory authority, may also be considered a primary stakeholder. A secondary stakeholder is a party that would benefit from knowledge of the data or that would be impacted by the results but is not critical to establishing the registry. Treating clinicians and their patients could be considered secondary stakeholders. A partial list of possible stakeholders, both primary and secondary, follows:

  • Public health or regulatory authorities.
  • Product manufacturers.
  • Health care service providers.
  • Payer or commissioning authorities.
  • Patients and/or advocacy groups.
  • Treating clinician groups.
  • Academic institutions or consortia.
  • Professional societies.

Although interactions with potential stakeholders will vary, the registry will be best supported by defined interactions and communications with these parties. Defining these interactions during the planning stage will ensure that adequate dialog occurs and appropriate input is received to support the overall value of the registry. Interactions throughout the entire duration of the registry can also assure stakeholders that the registry is aligned with the purposes and goals that were set out during the planning stages and that the registry complies with all required guidances, rules, and/or regulations.

Assess Feasibility

A key element in determining the feasibility of developing a new registry relates to funding. Registries that meet the attributes described in this user’s guide will most likely require significant funding. The degree of expense incurred will be determined by the scope of the registry, the rigor of data collection, and any audits that may be required. The larger the number of sites, number of patients, and scope of data collected, and the greater the need for representation of a wide variety of patient characteristics, the greater the expense will be. In addition, the method of data collection will contribute to expense. Historically, electronic data collection has been more expensive to implement, but generally less expensive to maintain, than forms that are faxed and scanned or mailed;15 however, the cost difference for startup has been lessening. Funding will be affected by whether other relevant data sources and/or infrastructures exist that capture some of the information of interest; whether the registry adapts to new issues over time; and whether multiple funding sources participate. Funding needs should also be examined in terms of the projected life of the registry and/or its long-term sustainability.

There are many potential funding sources for registries. Funding sources are likely to want to share in planning and to provide input for the many choices that need to be made in the implementation plans. Funding sources may negotiate to receive access to deidentified data as a condition for their participation. Funding models for registries may vary significantly, and there is no preferred approach. Rather, the funding model for a registry should be dictated by the needs of the registry. Potential sources of funding include:

  • Government: Federal agencies, such as the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), Centers for Medicare & Medicaid Services (CMS), and State agencies, may be interested in a registry to determine long-term outcomes of agents, devices, groups of drugs, or procedures. While the pharmaceutical industry or device manufacturers collect most long-term data on drug and device safety, many research questions arise that could potentially be suitable for government funding, ranging from clinical or comparative effectiveness to natural history of disease to the performance of health care providers based on accepted measures of quality of care. To determine if an agency might be interested in funding a registry, look for Requests for Proposals (RFPs) on its Web site. An RFP posting or direct communication with the appropriate agency staff may provide a great deal of specific information as to how a submission will be judged and what criteria would be needed in order for a proposal to be favorably ranked. Even if an RFP is not posted, contacting the appropriate agency staff may uncover potential interest in a registry to fill an unmet need.
  • Product manufacturers: Product manufacturers may be interested in studying the natural history of the disease for which they have (or are developing) a product; demonstrating the effectiveness and/or safety of existing products in real-world use through Risk Evaluation and Mitigation Strategy (REMS) programs as part of postmarketing commitments or requirements, or through studies; or assisting providers in evaluating or improving quality of care.
  • Foundations: Nonprofit disease foundations may be interested in a registry to track the natural history of the disease of interest as well as the impact of therapeutic interventions. Registries may be used to track practice patterns and outcomes for quality improvement initiatives. Ongoing registries can sometimes serve the additional purpose of assisting in recruitment for clinical trials.16
  • Private funding: Private philanthropic individuals or charitable foundations and trusts may have an interest in furthering research to better understand the effects of a particular intervention or sets of interventions on a disease process.
  • Health plan providers: Under certain circumstances, health plan providers may be interested in funding a registry, since practical clinical research is increasingly viewed as a useful tool for providing evidence for health coverage and health care decisions.17
  • Professional societies: Health care professional associations are increasingly participating in developing or partnering with registries for scientific and quality measurement or improvement purposes.
  • Professional society/pharmaceutical industry “hybrids”: Situations may exist in which a product manufacturer funds a registry designed and implemented by a professional society to gain insight into a set of research questions.
  • Multiple sponsors: Registries may meet the goals of multiple stakeholders, and such stakeholders may have an interest in sharing the funding. Registries for isotretinoin and antiretrovirals in pregnancy are examples. While multiple sponsorship can decrease the costs for each funding source, their varied interests and needs almost always increase the complexity and overall cost of the registry.

A public-private partnership is a service or business venture that is funded and operated through a partnership (contractual agreement) between a public agency (Federal, State, or local) and a private-sector entity or entities.18 (See Case Example 4.) While some true public-private partnerships for registries currently exist (e.g., State-level immunization registries, bioterrorism surveillance),19,20,21 there is great potential for growth in this approach. Both government and private sources have shown increasing interest in registries for improved safety monitoring, for comparative effectiveness goals, and for streamlining the costs of the drug development process.22,23,24,25,26,27 Several legislative actions have stated or suggested the role of public-private partnerships for activities such as registry development.28 There are many reasons for multiple stakeholders, including government agencies, providers, and industry, to be interested in working together on particular registries for certain purposes. Thus, it is anticipated that shared funding mechanisms are likely to become more common.

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Case Example 4

Using a Collaborative Approach To Plan and Implement a Registry. In 2003, an NHLBI working group was convened to prioritize recommendations for optimizing outcomes in patients receiving left ventricular assist device (LVAD) therapy, a specific type of (more...)

Build a Registry Team

Several different kinds of knowledge, expertise, and skills are needed to plan and implement a registry. In a small registry run by a single individual, consultants may be able to provide the critical levels of expertise needed to plan all components of the registry. In a large registry, a variety of individuals may work together as a team to contribute the necessary expertise. Depending on the size, scope, and purpose of the registry, few, some, or all of the individuals representing the components of expertise described below may be included at the time of the planning process. Whatever number of individuals is eventually assembled, it is important to build a group that can work together as a collegial team to accomplish the goals of the registry. Additionally, the team participants must understand the data sources. By understanding the goals and data sources, the registry team will enable the data to be utilized in the most appropriate context for the most appropriate interpretation. The different kinds of expertise and experience that are useful include the following:

  • Project management: Project management will be needed to coordinate the components of the registry; to manage timelines, milestones, deliverables, and budgets; and to ensure communication with sites, stakeholders, oversight committees, and funding sources. Ongoing oversight of the entire process will require a team approach. (See Establish a Governance and Oversight Plan.)
  • Subject matter: A registry must be designed so that it contains the appropriate data to meet its goals as well as the needs of its stakeholders. For example, experts in the treatment of the clinical disease to be studied who are also familiar with the potential toxicities of the treatment(s) to be studied are critical to the success of the registry. Clinical experts must be able to apply all of the latest published clinical, toxicity, and outcome data to components of the registry and determine which elements are necessary, desirable, or superfluous.
  • Registry science: Epidemiology and biostatistics expertise specific to the subtleties of patient registries and observational research are very important in the design, implementation, and analysis of registry data. Epidemiologists can provide the study design and can work in collaboration with biostatisticians to develop a mutual understanding of the research objectives and data needed. Health outcomes researchers and economics researchers can also lend valuable expertise to the registry team. These scientists should work with the subject matter experts to ensure that appropriate analytic methods are being used to address the clinical issues relevant to achieving the goals of the registry.
  • Data collection and database management: The decision to include various data elements can be made in consultation with experts in this field to place “critical fields” in a prominent and logical position on the data form for both paper-based and electronic data collection tools. (A final determination of what is usable and workable for data collection tools should be approved by all members of the team.) These experts may also need to write specific programs so that the data received from the registry are grouped, stored, and identified. They may generate reports for individuals who track registry participation, and they may provide data downloads periodically to registry analysts. This team will also be responsible for implementing and maintaining firewalls to protect the data according to accepted levels of security for similar collections of sensitive data.
  • Legal/patient privacy: In the present legal climate, it is critical that either information that identifies individual patients be excluded or specific consent be sought to include information on the identity of a patient. The complexities of this topic are dealt with in detail in Chapter 8. Legal and privacy expertise is needed to protect the patients and the owners of the database by ensuring that the registry complies with all national and local laws applicable to patient information.
  • Quality assurance: As discussed in Chapter 10, quality assurance of procedures and data is another important component of registry success. Expertise in quality assurance will help in planning a good registry. The goals for quality assurance should be established for each registry, and the efforts made and the results achieved should be described.

Establish a Governance and Oversight Plan

Governance refers to guidance and high-level decisionmaking, including concept, funding, execution, and dissemination of information. A goal of proper governance and oversight should be transparency to stakeholders in operations, decisionmaking, and reporting of results.

The composition and relative mix of stakeholders and experts relate largely to the purpose of the registry. For example, if the purpose of the registry is to determine a comparative effectiveness or reimbursement policy, those impacted by the policy should not solely govern the registry. Broad stakeholder involvement is most desirable in governance boards when there are many stakeholders. Depending on the size of the registry, governance may be assumed by various oversight committees made up of interested individuals who are part of the design team (internal governance) or who remain external to the day-to-day operations of the registry (external governance). Differences in the nature of the study questions, the overall resources being consumed by the registry, the soundness of the underlying data sources, and many other factors will influence the degree of involvement and role of oversight groups. In other words, the purpose of the committee functions described below is to lay out the roles that need to be assumed by the governance structure of many registries, but these should be individualized for a particular registry. It is also possible, if methods are clear and transparent, that oversight requirements may be minimal.

Registries fulfill governance roles in a variety of ways. Many of the roles, for example, could be assumed by a single committee (e.g., a steering committee) in some registries. Whatever model is adopted, it must accommodate all of the working constituencies and provide a mechanism for these individuals to work together to achieve the goals of the registry.

All aspects of governance should be codified in a written format that can be reviewed, shared, and refined over time. In addition, governance is a dynamic process, subject to change in policy as evidence emerges that is likely to lead to improvements in the process.

Governance and oversight functions that may be considered include:

  • Executive or steering: This function assumes responsibility for the major financial, administrative, legal/ethical, and scientific decisions that determine the direction of the registry. These decisions are made with appropriate input from legal, scientific, and administrative experts. Depending on their capabilities and the size and resources of the registry, the group serving the steering function may also assume some of the functions described below.
  • Scientific: This function may include experts in areas ranging from database content, to general clinical research, to epidemiology and biostatistics. This function may determine the overall direction of database inquiries and recommend specific analyses to the executive or steering group. It is strongly desirable that the reports that emerge from a registry be scientifically based analyses that are independent and transparent.29 To enhance credibility and in the interest of full disclosure, the role of all stakeholders in the publication process should be specified and any potential conflicts of interest identified.
  • Liaison: In large registries, a function may be specified to focus on maintaining relationships with the funding source, health care providers, and patients who utilize the database. The group serving this function may develop monitoring and satisfaction tools to assure that the day-today operations of the registry remain healthy.
  • Adjudication: Adjudication is used to review and confirm cases (outcomes) that may be difficult to classify. Individuals performing this function are generally blinded to the exposure (product or process) under study so that the confirmation of outcomes is made without knowledge of exposure.
  • External review: External review committees, advisory boards, or data safety monitoring boards (DSMBs) can be useful for providing independent oversight throughout the course of the registry. The majority of registries will not require a DSMB, since a DSMB is commonly used in situations where data are randomized and treatment status is blinded. However, there may be situations in which the registry is responsible for the primary accumulation of safety data on a particular intervention; in such situations, an external committee or DSMB would be useful for conducting periodic reviews (e.g., annually).
  • Data access, use, and publications: This function should address the process by which registry investigators access and perform analyses of registry data for the purpose of submitting abstracts to scientific meetings and developing manuscripts for peer-reviewed journal submission. Authorship (including that of registry sponsors) in scientific publications should satisfy the conditions of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals.30 The rules governing authorship may be affected by the funding source, as in the case of NIH or foundation funding, or by the biomedical journal. (See Case Examples 2 and 5.) Other investigators may request permission to access the data. For example, a Ph.D. candidate at an institution might seek registry-wide aggregate data for the purpose of evaluating a new scientific question. A process for reviewing and responding to such requests from other investigators should be considered in some registries that may generate broad external interest if the registry stakeholders and participants are agreeable to such use.
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Case Example 5

Using a Scientific Advisory Board To Support Investigator Research Projects. The National LymphoCare Study includes a large number of community-based sites in addition to many academic sites. Many of the principal investigators at the community-based (more...)

Consider the Scope and Rigor Needed

Scope of Data

The scope of a registry may be viewed in terms of size, setting, duration, geography, and financing. The purpose and objectives of the registry should frame the scope, but other factors (aside from feasibility) may ultimately shape it. For example, the scope may be affected by:

  • Regulatory requirements, such as those imposed by the FDA as a condition of product marketing.
  • Reimbursement decisions, such as national coverage decisions by CMS or “Prior Authorization” requirements used by health insurers in some situations.
  • National research interests, such as those driven by NIH.
  • Public health policy, such as CDC policy and immunization policy.

The scope is also affected by the degree of uncertainty that is acceptable to the primary stakeholders, with that uncertainty being principally driven by the quantity, quality, and detail of the data collection balanced against its considered importance and value. Therefore, it is critical to understand the potential questions that may or may not be answerable because of the quantity and quality of the data. It should also be noted that the broader the audience of stakeholders is, the broader will be the list of questions that may need to be included. This increased breadth can result in an increase in the number of patients who need to be enrolled and/or data points that need to be collected in order to meet the objective of the registry with an acceptable level of precision.

Some of the specific variables that can characterize the scope of a registry include:

  • Size: This may refer to the number and complexity of data points or to the enrollment of investigators and patients. A registry with a large number of complex data points may allow for detailed and thoughtful analyses but may be so burdensome as to discourage investigator and patient enrollments. In turn, a small registry with few patients and data points may be easier to execute, but the data could lack depth and be less meaningful.31 Size also determines the precision with which measures of risk or risk difference can be calculated.
  • Setting: This refers to the specific setting through which the registry will recruit investigators and patients as well as collect data (e.g., hospital, doctor’s office, pharmacy, home).
  • Duration: The planning of a registry must reflect the length of time that the registry is expected to collect the data in order to achieve its purpose and provide analysis of the data collected. An example of a relevant factor is whether a product is nearing the end of the life of its patent.
  • Geography: The setup, management, and analysis of a locally run registry represent a very different scope than the setup, management, and analysis of a global registry. A global registry poses challenges (e.g., language, cultural, time zone, regulatory) that must be taken into consideration in the planning process.
  • Cost: The scope of a registry will determine the cost of creating, managing, and analyzing the registry. Budgetary constraints must be carefully considered before moving from conception to reality. Additionally, the value of the information is a factor in the financial decisions. The cost of the registry should be less than (or at a minimum, equal to) the projected value gained through the information generated. Certain choices in planning, such as building on existing infrastructure and/or linking to data sources relevant to the purposes of the registry, may increase the net return.
  • Richness of clinical data needed: In some situations, the outcome may be relatively simple to characterize (e.g., death). In other cases, the focus of interest may be a complex set of symptoms and measurements (e.g., for Churg-Strauss Syndrome) or may require specialized diagnostic testing or tissue sampling (e.g., sentinel node in melanoma). Some outcomes may require assessment by an independent third party. (See Scientific Rigor, below.)

When Data Need To Be Available for Analysis

Meaningful data on disease progression or other long-term patient outcomes may not be available through a registry for many years, whereas safety data could be analyzed on a rolling basis. Therefore, the type of data on patient outcomes and when they will be available for analysis should be addressed from the perspective of the intended uses of the data in both the short term and long term. For industry-sponsored registries, if planning begins at an early stage, it may be possible to consider whether to align registry questions with those from the clinical trial (where appropriate) so that some data can carry over for more comprehensive longitudinal analyses.

Scientific Rigor

The content of the data to be collected should be driven by the scientific analyses that are planned for the registry, which, in turn, are determined by the specific objectives of the registry. A registry that is designed primarily for monitoring safety will inevitably contain different data elements from one that is designed primarily for monitoring effectiveness. Similarly, the extent to which data need to be validated will depend on the purpose of the registry and the complexity of the clinical information being sought. For some outcomes, clinical diagnosis may be sufficient; for others, supporting documents from hospitalizations, referrals, or biopsies may be needed; and for others, formal adjudication by a committee may be required. Generally, registries that are undertaken for regulatory decisionmaking will require increased attention toward diagnostic confirmation (i.e., enhanced scientific rigor).

Define the Core Dataset, Patient Outcomes, and Target Population

Core Dataset

Elements of data to be included must have potential value in the context of the current scientific and clinical climate and must be chosen by a team of experts, preferably with input from experts in biostatistics and epidemiology. Each data element should relate to the purpose and specific objectives of the registry. Ideally, each data element should address the central questions for which the registry was designed. It is useful to consider the generalizability of the information collected, as appropriate. For example, when seeking information on cost-effectiveness, it may be preferable to collect data on resource utilization rather than actual costs of this utilization, since the broader descriptor can be more easily generalized to other settings and cost structures. While a certain number of speculative fields may be desired to generate and explore hypotheses, these must be balanced against the risk of overburdening sites with capturing superfluous data. A plan for quality assurance should be considered in tandem with developing the core dataset.

The core dataset variables (“need to know”) define the information set needed to address the critical questions for which the registry was created. At a minimum, when calculating the resource needs and overall design of the registry, registry planners must account for these fields. If additional noncore variables (“nice to know”) are included, such as more descriptive or exploratory variables, it is important that such data elements align with the goals of the registry and take into account the burden of data collection and entry at the site level. A parsimonious use of “nice to know” variables is important for several reasons.

First, when data elements change, there is a cascade effect to all dependent components of the registry process and outputs. For example, the addition of new data elements may require changes to the data collection system, retraining of site personnel on data definitions and collection practices, adjustments to the registry protocol, and amendment submissions to institutional review boards. Such changes often require additional financial resources. Ideally, the registry would both limit the total number of data elements and include, at the outset, data elements that might change from “nice to know” to “need to know” during the course of the registry. In practice, this is a difficult balance to achieve, so most registries should plan adequate resources to be used for change management.

Second, a registry should avoid attempting to accomplish too many goals, or its burden will outweigh its usefulness to the clinical sites and researchers. Examples exist, however, of registries that serve multiple purposes successfully without overburdening clinicians. (See Case Example 2.)

Third, even “need-to-know” variables can sometimes be difficult to collect reliably (e.g., use of illegal substances) or without substantial burden (e.g., unusual laboratory tests). Even with a limited core dataset, feasibility must still be considered. (See Chapter 5.)

Fourth, it is useful to consider what data are already available and/or collected and what data need to be additionally collected. When determining data elements that will be additionally collected, it is imperative to consider whether the information desired is consistent with general practice or whether it might be considered “interventional” rather than observational. The distinction between “interventional” and “observational” is challenging to many. According to Chapter 1.7.1 of Volume 9A of the Rules Governing Medicinal Products in the European Union,32 registries may “collect a battery of information using standardized questionnaires in a prospective fashion” and “questionnaires, by themselves, are not considered interventional.” These rules also state that

  • “[T]he assignment of a patient to a particular strategy is not decided in advance by a [trial] protocol but falls within the current practice…”
  • “[N]o additional diagnostic or monitoring procedures shall be applied to patients.”

This last requirement can be challenging to interpret since registries sometimes perform diagnostic tests that are consistent with general practice but may be performed more frequently than would be the case in general practice.

Finally, it is important to consider patient privacy, national and international rules concerning ethics, and regulatory requirements to assure that the registry data requirements do not jeopardize patient privacy or put institutional/ethics reviews and approvals at risk.

Patient Outcomes

The outcomes of greatest importance should be identified early in the concept phase of the registry. Delineating these outcomes (e.g., primary or secondary endpoints) will force registry designers to establish priorities. Prioritization of interests in the planning phase will help focus the work of the registry and will guide study size requirements. (See Chapter 3.) Identifying the patient outcomes of the greatest importance will also help to guide the selection of the dataset. Avoiding the temptation to collect “nice to know” data that are likely of marginal value is of paramount importance, yet some registries do, in fact, need to collect large amounts of data to accomplish their purposes. Possessing adequate data in order to properly address potential confounders during analyses is one reason that extensive data collection is sometimes required.33

Methods to ascertain the principal outcomes should be clearly established. The diagnostic requirements, level of data detail, and level of data validation and/or adjudication should also be addressed. As noted below in the context of identifying a target population, relying on established guidelines and standards to aid in defining outcomes of interest has many benefits and should be considered.

The issues of ascertainment noted here are important to consider because they will have a bearing on some attributes by which registries may be evaluated.34 These attributes include sensitivity (the extent to which the methods identify all outcomes of interest) and external validity (generalizability to similar populations), among others.

Target Population

The target population is the population to which the findings of the registry are meant to apply. It must be defined for two basic reasons. First, the target population serves as the foundation for planning the registry. Second, it also represents a major constituency that will be impacted by the results of the registry.

One of the goals for registry data may be to enable generalization of conclusions from clinical research on narrowly defined populations to broader ones, and therefore the inclusion criteria for most (although not all) registries are relatively broad. As an example, screening criteria for a registry may allow inclusion of elderly patients, patients with multiple comorbidities, patients on multiple therapies, patients who switch treatments during the period of observation, or patients who are using products “off label.” The definition of the target population will depend on many factors (e.g., scope and cost), but ultimately will be driven by the purpose of the registry.

As with defining patient outcomes, target population criteria and/or definitions should be consistent with established guidelines and standards within the therapeutic area. Achieving this goal increases the potential utility of the registry by leveraging other data sources (historical or concurrent) with different information on the same target population and enhancing statistical power if similar information is collected on the target population.

In establishing target population criteria, consideration should be given to the feasibility of access to that population. One should try to distinguish the ideal from the real. Some questions to consider in this regard are:

  • How common is the exposure or disease of interest?
  • Can eligible persons be readily identified?
  • Are other sources competing for data on the same patients?
  • Is care centralized or dispersed (e.g., in a referral or tertiary care facility)?
  • How mobile is the target population?

Ultimately, methods to ascertain members of the target population should be carefully considered (e.g., use of screening logs that identify all potential patients and indicate whether they participate and, if not, why not), as should the use of sources outside the registry (e.g., patient groups). Greater accessibility to the target population will reap benefits in terms of enhanced representativeness and statistical power.

Lastly, thought should be given to comparison (control) groups either internal or external to the registry. Again, much of this consideration will be driven by the purpose and specific objectives of the registry. For example, natural history registries do not need controls, but controls are especially desirable for registries created to evaluate comparative effectiveness or safety.

Develop a Study Plan or Protocol

The study plan documents the objectives of the registry and describes how those objectives will be achieved. At a minimum, the study plan should include the registry objectives, the eligibility criteria for participants, and the data collection procedures. Ideally, a full study protocol will be developed to document the objectives, design, participant inclusion/exclusion criteria, outcomes of interest, data to be collected, data collection procedures, governance procedures, and plans for complying with ethical obligations and protecting patient privacy.

In addition to a study plan or protocol, registries may have statistical analysis plans. Chapters 13 and 14 discuss the importance of analysis plans.

Develop a Project Plan

Developing an overall project plan is critically important so that the registry team has a roadmap to guide their collective efforts. Depending on the complexity of the registry project, the project plan may include some or all of the following elements:

  • Scope management plan to control the scope of the project. It should provide the approach to making changes to the scope through a clearly defined change-control system.
  • Detailed timeline and schedule management plan to ensure that the project and its deliverables are completed on time.
  • Cost management plan for keeping project costs within the budget. The cost management plan may provide estimates on cost of labor, purchases and acquisitions, compliance with regulatory requirements, etc. This plan should be aligned with the change-control system so that all changes to the scope will be reflected in the cost component of the registry project.
  • Quality management plan to describe the procedures to be used to test project concepts, ideas, and decisions in the process of building a registry. Having a quality management plan in place can help in detecting design errors early, formulating necessary changes to the scope, and ensuring that the final product meets stakeholders’ expectations.
  • Staffing management plan to determine what skills will be needed and when to meet the project goals. (See previous section, Build a Registry Team).
  • Communication plan that includes who is responsible for communicating information and to whom it should be communicated. Considerations include different categories of information, frequency of communications, and methods of communication. It also should provide steps to escalate issues that cannot be resolved on a lower staff level.
  • Procurement plan for external components or equipment and/or outsourced software development for the planned registry, if pertinent. Such a plan should describe how the procurement process will be managed within the organization. Decisions to procure products or services may have a direct impact on other components of the project plan, including the staffing plan and timeline.
  • Risk management plan to identify and mitigate risks. Many project risks are predictable events, and therefore they can and should be assessed in the very early stages of registry planning. It is important to prioritize project risks by their potential impact on the specific objectives and to develop an adequate risk response plan for the most significant risks. Some predictable risks include:

    Disagreement between stakeholders over the scope of specific tasks.

    Inaccurate cost estimates.

    Delays in the timeline.

Determine What Will Happen When the Registry Ends

Most registries have a finite lifespan. A registry that tests the safety of a product used during pregnancy will have a different lifespan from one that examines the effectiveness of new interventions in a chronic disease. Sponsors and registry participants should have an understanding of the proposed lifespan of the registry at the time of its inception or at least have developed some contingency plans, such as “if/then” alternatives.

The determination of who owns the data at the end of the natural lifespan of the registry and where the data are to be stored should also be defined at the time of registry inception. Possibilities include the principal investigator, the sponsor or funding source, or a related professional society. Chapter 8 discusses issues of ownership.

Registries that generate continuing societal value, such as quality improvement programs and safety programs, might consider transitions that continue the registry functions after the original funding sources have expired.

For a more detailed discussion, see Planning for the End of a Patient Registry, below, and Case Example 6.

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Case Example 6

Determining When To Stop an Open-Ended Registry. Bupropion, an antidepressant with the potential for prenatal exposure, was labeled with a pregnancy category C by the U.S. Food and Drug Administration (FDA) due to prior animal data. The manufacturer established (more...)

Planning for the End of a Patient Registry

Once a registry is in place, how long should it continue? What are reasonable decision criteria for stopping data collection? This section considers the issues related to stopping a patient registry study and suggests some guidelines. Although the specific answers to these questions will vary from study to study, the types of considerations may be more general. The discussion here is focused on registries intended to assess specific safety or effectiveness outcomes rather than those intended to assess health care operations, such as continuous quality improvement.

When Should a Patient Registry End?

Stopping an Experiment

The principles regarding rules for stopping a study mostly stem from the need to consider stopping an experiment. Because experiments differ from registries in crucial ways, it is important to distinguish between the issues involved in stopping an experimental study and in stopping a nonexperimental study. In an experiment, the patient’s treatment is determined by the study protocol, which typically involves random assignment to a treatment regimen. In a nonexperimental study, patients are treated according to the treatment protocol devised by their own clinician, typically uninfluenced by the study. In a randomized trial of a new therapeutic agent or a field trial for a vaccine, the size of the study population is ordinarily set in the study protocol, based on assumptions about the expected or hypothesized results and the study size needed to reach a reasonable scientific conclusion. Ordinarily this planned study size is based on power calculations, which require as input the criteria for statistical significance, the effect size anticipated, the baseline occurrence rate of the study outcome, and the relative size of the study arms. Because of inherent problems in relying on statistical significance for inference, the study size preferably will be planned around estimation of effect and the desired level of precision. In a study intended to provide some reassurance about the safety of an agent, the study size may be planned to provide a specific probability that the upper confidence bound of a conventional confidence interval measuring an adverse effect would be less than some specified value, given a postulated value for the effect itself (such as no effect). In the latter situation, if no effect is anticipated, a power calculation is not only unreasonable but is not even possible, whereas planning a study on the basis of precision of estimation is always possible and always reasonable.

Stopping an experiment earlier than planned is an important decision that is typically made by an advisory group, such as a data safety and monitoring board, which is constituted to monitor study results and make decisions about early stopping. In a biomedical experiment, the investigator has a greater ethical obligation than in a nonexperimental study to safeguard the well-being of study participants. This is because the investigator is administering an intervention to study participants that is expected to affect the probability that study participants will experience one or more specific health outcomes.

Equipoise is a widely accepted (but, unfortunately, not universally accepted) ethical precept regarding human biomedical experimentation. Equipoise requires that at the outset of the study, the investigator has a neutral outlook regarding which of the study groups would fare better. A strict interpretation of equipoise requires each of the study investigators to be in a state of equipoise. An alternative view, referred to as “clinical equipoise,” is that equipoise can be achieved at the group level, with the enthusiasm of some investigators for the prospects of the study intervention being balanced by the skepticism of others. Whichever interpretation of equipoise is adopted, most investigators agree that if equipoise becomes untenable as study results accumulate, the study should be stopped to avoid depriving some study participants of a potential benefit relative to what other participants receive.

For an advisory board to decide to stop a study early, there must be solid evidence of a difference between the groups before the planned study endpoint is reached. Such stopping decisions are usually based on ethical concerns, as scientific considerations would seldom dictate an early stop to a study that had been planned to reach a specific size. Advisory boards must base stopping decisions on analyses of accumulating study data, which are usually formally presented at regular meetings of the review board. Statistical concerns have been raised about biases that can arise from repeated analyses of accumulating data. To offset these concerns, many experiments are planned with only a limited number of interim analyses, and the interpretation of study results takes into account the number of interim analyses.

Stopping a Fixed-Length Nonexperimental Study

Like experiments, most nonexperimental studies also have a fixed time for their conduct and a planned size that reflects goals analogous to those in experimental studies. Nevertheless, the ethical concerns that motivate stopping an experiment before its planned completion do not have a direct counterpart in nonexperimental studies. Nonexperimental studies do have ethical concerns, but they relate to issues such as data privacy, intrusive questioning, or excessive inducements for participation rather than to concerns about intervention in the lives of the participants. Although it is theoretically reasonable that an investigator could choose to stop a nonexperimental study for ethical reasons, those reasons would presumably relate to ethical problems that were discovered in the course of the study but were unrecognized at the outset rather than to an early conclusion regarding the study goal. The investigator in a nonexperimental study could learn, from an interim analysis, that the association between the exposure and the outcome under study was much stronger than anticipated. Unlike the experimental setting, however, the investigator in a nonexperimental study is not administering the exposure to any of the study subjects and thus has no responsibility to the study subjects regarding their exposure.

The discovery of an ethical problem during the conduct of a nonexperimental study is therefore possible but extremely rare. Because the findings from an interim analysis should not lead to discontinuation of a nonexperimental study, there is little motivation to conduct interim analyses for nonexperimental studies that have been planned with a fixed size and period of execution. If there is some considerable time value to the findings, such as to inform regulatory action, it might be worthwhile to conduct an interim analysis in a nonexperimental study to get an early appraisal of study findings. Unless there is an appropriate outlet for releasing interim findings, however, it is possible that early findings will not circulate beyond the circle of investigators. In most circumstances, such analyses are hard to justify in light of the fact that they are based on a smaller amount of data than was judged appropriate when the study was planned; thus the originally planned analysis based on all the collected data will still need to be conducted. Unless there is a clear public health case to publicize interim results, journal policies that require that published data have not been previously published may inhibit any release of preliminary findings to news media or to journals in the form of preliminary findings.

Stopping an Open-Ended Study

Although patient registries may be undertaken with a fixed length or size, or both, based on study goals relating to specific safety or efficacy hypotheses, many such studies are begun as open-ended enterprises without a planned stopping point. For example, patient registries without specific hypotheses may be undertaken to monitor the safety of patients receiving a novel therapy. The Antiepileptic Drug Pregnancy Registry, established in 1997, is an example of an open-ended registry that focuses on a set of specific endpoints (congenital malformations) among a subset of patients (pregnant women) taking a class of medications (antiepileptic drugs). It has no fixed stopping point.

Measuring the frequency of rare endpoints demands large study sizes. Therefore, a monitoring system that includes rare endpoints may have to run for a long while before the accumulated data will be informative for low-frequency events. On the other hand, the lower the frequency of an adverse event, even one with serious consequences, the smaller is the public health problem that a relative excess of such events would represent.

Traditional surveillance systems are intended to continue indefinitely because they are intended to monitor changes in event frequency over time. For example, surveillance systems for epidemic infectious diseases provide early warning about outbreaks and help direct efforts to contain such outbreaks. In contrast, a patient registry is not a true surveillance system, since most are not intended to provide an early warning of a change in outcome frequency. Rather, most patient registries are intended to compile data on outcomes associated with novel treatments, to supplement the sparse data usually available at the time that these treatments are considered for approval by regulatory agencies. For example, a regulatory agency might mandate a patient registry as a condition of approval to supplement safety information that was submitted during the application process.

How long should such a registry continue? Although it is not possible to supply a general answer to this question, there is little reason to support a registry continuing indefinitely unless there is a suspicion that the treatments or treatment effects will change over time. Otherwise, the time should come when the number of patients studied suffices to answer the questions that motivated the registry. The Acyclovir Pregnancy Registry, which began in 1984, was stopped in 1999. Its advisory committee concluded: “The [Acyclovir Pregnancy] Registry findings to date do not show an increase in the number of birth defects identified among the prospective reports [of exposures to acyclovir] when compared with those expected in the general population. In addition, there is no pattern of defects among prospective or retrospective acyclovir reports. These findings should provide some assurance in counseling women following prenatal exposure [to acyclovir].” The consensus was that additional information would not add materially to the information that had already been collected, and thus the registry was closed down.

To avoid uncertainty about the fate of an open-ended study, it would be sensible to formulate a specific goal that permits a satisfactory conclusion to data collection. Such a goal might be, for example, the observation of a minimum number of specific adverse events of some type. Even better would be to plan to continue data collection until the upper bound of a confidence interval for the rate or risk of the key outcome falls below some threshold or until the lower bound falls above a threshold. Analogous stopping guidelines could be formulated for registry studies that are designed with a built-in comparison group.

Decisions on Stopping and Registry Goals

Ideally, stopping decisions ought to evaluate data from a registry against its stated goals. Thus, the registry protocol or charter should include one or more specific and measurable endpoints against which to judge whether the project should continue or stop. Without that guidance, any decision to discontinue a registry may appear arbitrary and will be more readily subject to political considerations. In cases where there are no measurable endpoints to use in making the decision, it is important that any final reports or publications linked to the registry include a clear discussion of the reasons for stopping it.

Registry goals will vary according to the motivation for undertaking the project and the source of funding. Product-specific registries may be created as postapproval regulatory commitments. For products about which there are limited preapproval safety data, the wish for additional comfort about the product’s safety profile can be translated into a measurable goal. Such a goal might be to exclude the occurrence of life-threatening or fatal drug-related events at a certain frequency. For example, the goal could be to establish a specified level of confidence that unexplained hepatic necrosis in the 3 months following drug exposure occurs in less than 1 patient in 1,000. Alternatively, the goal might be to provide a more precise estimate of the frequency of a previously identified risk, such as anaphylaxis. Ideally, this goal should be formulated in specific numeric terms. With specific goals, the registry can have a planned target and will not be open ended.

If a registry study does not have a single or very limited set of primary objectives, a stopping point will be more challenging to plan and to justify. Even so, with measurable goals for some endpoints, it will be possible to determine whether the registry has achieved a core purpose and may lead to a reasonable stopping point. Conversely, a registry that fails to meet measurable goals and appears to be unable to meet them in a reasonable time is also a candidate to be stopped. For example, if the registry faces unexpectedly low patient accrual, it should be stopped, as was done with the Observational Familial Adenomatous Polyposis Registry Study in Patients Receiving Celecoxib. This study enrolled only 72 patients in 4 years, out of a planned 200 during 5 years. Another reason to consider stopping is incomplete or poor-quality information. Poor-quality data are of particular concern when the data regard sensitive or illegal behavior, such as self-reported information on sexual practices. Decisions about stopping a registry because of low enrollment or inadequate information are made simpler with clearly stated goals regarding both features of the study. The criteria for useful quantity and quality of information should be specified at the outset. How well the study meets the criteria can be assessed periodically during data collection.

A registry may outlive the question it was created to answer. For example, if use of the product is superseded by another treatment, the questions that drove the creation of the registry may no longer be relevant, in which case it may best be retired. For medical devices, for example, newer technology is continuously replacing the old, although safety issues for older technology may motivate continuing a registry of an outmoded technology. A related issue arises when the question of interest evolves as data collection proceeds. Stopping or continuing the registry depends on whether it can address the changing goal or goals. That, in turn, depends on whether the governance of the registry provides adequate flexibility to refocus the registry in a new direction.

The decision to stop a registry may also depend on mundane considerations such as cost or staffing. For long-running registries, eventually the value of new information may face diminishing returns. Some registries have central core staff, deeply committed to the registry, who serve as its historical memory. Departure of such individuals can cripple the registry’s function, and a decision to stop may be appropriate. Similarly, a cohort of engaged investigators may disperse over time or lose interest in the registry. Funding sources may dry up, making it impossible for the registry to function at a level that justifies its continued existence.

A thorny question concerns how a registry can continue with altered ownership or governance. Suppose a registry is formed with multiple stakeholders, and one or more withdraws for the reasons described above. For example, when the implantable cardioverter defibrillator (ICD) registry was formed, it came about in response to a CMS Coverage with Evidence Development decision. The Heart Rhythm Society and the American College of Cardiology developed the registry with funding from industry to help institutions meet the need for registry participation for payment purposes, and they layered quality improvement and research goals onto that mandate. The resulting registry was rapidly integrated into more than 2,000 institutions in the United States. If CMS determines that the ICD registry is no longer needed for its purposes, the registry must determine if it will continue as a quality improvement program and whether to add other stakeholders and funding sources or participation drivers (such as manufacturers, insurers, or other government agencies such as FDA).

What Happens When a Registry Ends?

Stopping a registry might mean ceasing all information collection and issuing a final report. An intermediate decision that falls short of a full stop might involve ceasing to accrue new patients while continuing to collect information on existing participants. This step may be useful if the registry goals are in the process of changing. If a registry is to be stopped, the archiving rules should be checked and followed, so that those who need to consult the data for questions not fully addressed in reports or publications can get their answers later, provided that the charter of the registry allows it. Following German reunification in 1990, it was determined that the East German National Cancer Registry, which had received detailed reports on 2 million cancer cases from 1954 to 1990, was in violation of West German privacy laws, and the data were quarantined. In the more usual case, orderly archiving of the data in anticipation of later access should be part of the close-down procedure, in a manner consistent with the charter under which the data were collected.

A slightly different scenario occurs when the registry has a single sponsor whose purposes have been achieved or determined to be unachievable and the sponsor decides to end the registry. Is there an obligation to patients or participating providers to continue the registry because some value (e.g., quality improvement, data for other comparisons) can still be derived? It is difficult to argue that the sponsor has an ongoing financial responsibility once the registry has achieved or failed to achieve its primary purpose, especially if this has been spelled out in the protocol and informed consent. Yet one can argue that, to the extent that it is feasible and affordable to engage other stakeholders in discussions of potential transitioning of the registry to other owners, this approach should be encouraged. Nontrivial issues of data ownership, property, confidentiality, and patient privacy would need to be satisfactorily addressed to make such transitions possible, and therefore it is always best to consider this possibility early on in registry planning. Both the National Registry of Myocardial Infarction (NRMI), sponsored by Genentech, Inc., and the OPTIMIZE-HF registry, sponsored by GlaxoSmithKline, successfully completed transitions to other organizations (American College of Cardiology and American Heart Association, respectively) when those registries were concluded, providing their participating hospitals with the ability to continue the quality improvement efforts begun under those registries.

There is no clear ethical obligation to participants to continue a registry that has outlived its scientific usefulness. In fact, altering the purpose of a registry would be complicated unless the original registry operators were interested in doing so. For instance, if a registry is to be transferred, then it should be a restricted transfer (presumably a gift) to ensure that the permissions, terms, and conditions under which it was compiled continue to be satisfied. The participants should be notified and should determine if they will continue participation and allow their data to be used for this new purpose.

There are a few potential reasons to consider preserving registry data once the registry developers have determined that it should end. One reason is that the data may be capable of producing a recognized public health benefit that will continue if the registry does. Another situation may be that the registry has historical importance, such as a registry that tracks the outbreak of a novel infectious disease that may provide insight into the transmission of the disease, if not now, then sometime in the future. Longitudinal collections of data may also be useful for hypothesis generation.

In creating a registry, the investigators should plan what will happen to data when the registry ends. If a public health benefit might be realized from registry data, then archiving of registry data is a potential answer. Decisions must be made by the registry owners in careful consideration of other stakeholders and potential costs.

Summary

Experimental studies, such as clinical trials or field trials, come with a high ethical burden of responsibility, which includes periodically reevaluating the ethical basis for continuing the trial in the light of interim results. Consequently, trials require interim analyses and data safety monitoring boards, which decide whether the study should be stopped for ethical reasons. In nonexperimental studies, there is much less motivation to conduct interim analyses because there is no ethical motivation to do so. There is also no reason to appoint a data safety monitoring board, although any study could appoint an external advisory board. If nonexperimental studies are planned to be of fixed length or fixed study size, they can be conducted as planned without interim analyses, unless the time value of an early, interim analysis is important enough to compensate for the added cost of conducting it and the tentativeness of the findings, which are based on only a subset of the planned study data.

If a patient registry is undertaken as an open-ended project without a fixed endpoint, it need not continue forever. Unlike true surveillance efforts, patient registries of novel therapies are not intended to monitor changes in occurrence rates over time. Rather, they are conducted to assemble enough data to evaluate associations that could not be evaluated with the limited data available at the time of new product approval. Therefore, reasonable goals should be set for the amount of information to be collected in such registries, based on specific endpoints of interest. These goals can and should be cast in specific terms regarding data quality, study enrollment, and precision of the estimates of specific measures that the registry is intended to describe.

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