FormalPara Key Points for Decision Makers

Patient organizations are frequently encouraged by third parties to “build a registry” but are offered little guidance on whether that is the right decision, and if so, whether to build, buy, or borrow one from a platform provider.

Patient registries have the potential to serve a variety of stakeholders including patients, researchers, clinicians, pharmaceutical companies, and payers. By starting with the end in mind and identifying the aims and intentions of these stakeholders from the outset, the registry itself will be more useful for all concerned.

Setting up and maintaining a registry involves a range of costs including information technology staff, server costs, data management, and marketing. There are a range of approaches to obtaining initial funding (such as a grant or a consortium of industry sponsors) and maintaining ongoing support (such as cost recovery from academics or fee-for-service approaches).

With the advance of technology, the barriers to building a registry are becoming lower, but the expectations of patients and caregivers are growing higher as they have daily access to social networks, smartphones, and wearable devices. Privacy, interoperability, and the ability to move to another platform in the future are key technical considerations as you plan your activities.

1 Background

Patient registries are a relatively modern invention, dating back some 50 years and defined as “an organized system that uses observational study methods to collect uniform data (clinical and other) to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and that serves one or more predetermined scientific, clinical, or policy purposes” [1]. A registry differs from a simple “contact database” that might be used to store the personal details and basic demographics of people living with a medical condition for such purposes as mailing lists or fundraising. It is also different from a “study database” that might be developed while trying to answer a single scientific question for a single research study. Finally, it is different from the “forums” or “online support groups” found online that primarily exist to enable peer-peer communication, even though their proper function depends on a database too. Instead, a well-designed registry has much broader functions, in that it can potentially serve as the foundation for multiple studies from different disciplines that serve many stakeholders [1].

Traditionally, registries have fulfilled a variety of functions for clinicians, researchers, non-profit organizations, payers, and policy makers such as helping to understand the natural history of a poorly understood condition, determining the effectiveness of interventions outside the confines of a randomized controlled trial, measuring safety, and/or measuring quality [1]. More recently though, there has been growing interest in evolving registries from siloed databases purely intended for scientists to study into more dynamic systems that allow for the development of “learning health systems” to benefit many stakeholders [2]. Such progress includes increasing patient and caregiver involvement in governing a registry, connecting registry data to clinical care, and supporting advocacy for non-profit organizations looking to generate evidence [2].

We are a group of authors specializing in digital health research (PW), registry partnerships with patient organizations (LWE), setting up a patient organization’s first registry (SF), data governance and privacy issues for patients (AD), and regulations, registry development, and commercialization (EHD). Based on our experience in the USA and Europe, through the course of this education article we aim to provide an initial primer for leaders at patient organizations who might be considering setting up a patient registry for the first time. We will outline the potential benefits of developing a registry, cite some examples for review, outline technical considerations, describe data collection approaches, summarize ethical issues, suggest ways to make a registry commercially sustainable, and outline some of the key privacy issues involved.

2 The Promise and Potential of a Well-Designed Patient Registry

Given that there seem to be so many patient registries today, what are some of the potential benefits that others have experienced? There is opportunity to support four levels of beneficiaries: individuals, communities, organizations, and scientific fields.

At an individual level, a shared experience of all those affected by ill health is uncertainty. Common questions include: What is this thing I have? What will this do to me? What might help me get better [3]? Patients and family members seek a variety of sources to answer these questions including their healthcare providers, the medical/scientific community, and the experiences of other peers like them who have been down a similar path. However, most individuals quickly realize that there are no solid answers and that whatever information they gather is likely to be biased. Because registries have a scientific orientation towards collecting uniform data, they are the best chance we have to elevate individuals from “I” to a community of “We” in improving our shared understanding of a condition (Fig. 1). Beyond fulfilling their own needs, most patients and caregivers altruistically want their experiences to count for something, to be measured, and to be put to good use so that others might learn from their victories and their mistakes [4]. Being seen, being counted, and being connected are key drivers of value for a community. Whereas once, being part of the “patient community” meant being a formal member of a charitable organization or non-profit organization and attending in-person meetings or paying annual dues to receive newsletters, the changes brought by the Internet have broadened who counts as a member of a community. Increasingly, patient advocates use a variety of social networking platforms and can self-identify with a hashtag in their messages (e.g., #BCCW for Breast Cancer Chat Worldwide), a note of diagnosis on their profile (e.g., “breast cancer survivor”), or by interacting with other stakeholders informally in public or in private. The COVID-19 pandemic accelerated such developments, as shown for example by the Patient-Led Research Collaborative of people living with Long Covid who themselves are also researchers from around the world operating outside a formal organizational structure [5].

Fig. 1
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Example dashboard view for a patient registry participant showing real-time location of registrations. Through an engaged community of younger users on TikTok and Instagram, the registry quickly surpassed its target recruitment of N = 100 for the year in just over a month. Courtesy of Poland Syndrome Community Register and Pulse Infoframe

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At an organizational level, registries give authority and credibility for non-profit organizations to present data-driven insight and business cases. Governance and control over a registry act as powerful convening forces to attract external stakeholders who would like to learn more about a condition, such as pharmaceutical companies, funders, and policy makers. A registry is a tangible asset to attract investment, a rationale for professionalizing, and a mechanism for delivering impact. In collaborating with researchers, a registry lowers the barriers inherent in answering a range of questions. The provision of electronic surveys fielded easily through low-cost online tools expands the pool of research hypotheses that can be tested without needing to stand up their own data collection infrastructure. This can be important to answer questions relating to topics such as the health economic impact of disease [6], which might be important from a policy perspective but rarely attract as much research funding as interventional clinical trials, for instance. Where clinicians are tightly woven into the activity of a registry, it can become possible to conduct quality improvement work to better understand how care delivery and patient outcomes interact, and what can be done better [7].

Once a multi-national field of study and practice becomes large enough, it is not uncommon for there to be multiple (sometimes even competing) registries in a given condition. They might have originated in different geographies, fulfill different objectives, or even been developed as direct counter positioning (i.e., a non-profit version of a for-profit organization’s registry, or two different medicines each with their own safety registry). For example, some industry-funded registries only collect data specific to a single product, such as the Hunter Outcome Survey, which excludes potential participants who are not taking the funding manufacturer’s product [8]. In some fields, a higher order harmonization group can come together to ensure that similar core data elements are collected by multiple registries and to offer an integrated view [7, 9, 10].

Regulators are a key stakeholder and harmonizer of standards in the health field, and groups such as the European Medicines Agency Cross-Committee Task Force on Patient Registries provide guidance and advice on how to best structure registries [11]. Between 2005 and 2013, the European Medicines Agency requested that over 30 drug manufacturers develop a registry to inform long-term safety and risk-management profiles, particularly in rare or “orphan” diseases [11]. In the USA, the Food and Drug Administration has draft guidance for industry on how to ensure the quality of data captured can support regulatory decisions [12]. Even if your registry is not primarily intended to assess safety or the real-world efficacy of products, these regulatory guidelines may still be the standards by which pharmaceutical sponsors (and the scientists that work there) will judge the robustness of your registry data. Table 1 lists some well-regarded registries in the space across a range of size, age, and therapeutic area, each of which provide additional context and examples of best practice in governance, member engagement, and scientific outputs. They all have websites and scientific publications that can serve as templates and inspiration for planning your registry.

Table 1 Examples of patient registries that range in size, age, and focus
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3 Starting with the End in Mind

Throughout this Education article, we repeat the importance of starting with the end in mind. The point of a registry is not merely to collect data [13]. The point of a registry is to answer questions. The types of questions we can answer with a registry might include scientific, clinical, and policy concerns. Scientific questions might include: What sort of people have this disease? Where can we find people who might be eligible to enroll in clinical trials? Could we stratify patients into different forms of the disease, for example, moderate/severe? Clinical questions might include: How are the outcomes of people with this disease changing over time? What are the most important symptoms to manage? How well do drugs and other interventions work in this disease? Finally, policy questions might include: What sort of services and support are people seeking and getting? Is there enough funding being provided to support people with this condition nationally as well as locally? Are people with this disease still able to work, study, and be productive? If not, what is getting in their way? There are several different types of project associated with the word “registry” and Table 2 attempts to differentiate between the most common examples of terms used in the field, but these are not always applied consistently.

Table 2 Traditional origins for different types of registry (or similar concepts) and common terms. Definitions are not always used consistently over time, geographies, and disease areas
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Before you get started, it is worth searching for your condition and the word “registry” in scientific search engines such as PubMed or Google Scholar to see if there are already similar projects underway. It can also be worth searching for any recent “systematic reviews” of your disease field to identify what gaps remain to be filled in the literature. As you start thinking through your objectives for a patient registry, it can be useful to keep a list of these questions, because this will shape what data you collect, how large a sample you need, and how burdensome it might be to take on this endeavor. As you meet with other stakeholders, it is also important to interview them to understand what sort of questions they are hoping to answer with a registry. If you do not have all the context as to why they might want a particular question answered, dive a little deeper. The developers of the European Cystic Fibrosis Society Patient Registry caution against setting the community’s expectations too high or trying to capture too much information from the outset that will never be used [13]. For further information, and a helpful checklist, The Genetic Alliance has produced a detailed “Registry Bootcamp” (https://geneticalliance.org/registries/bootcamp) to support your efforts.

For example, once you have set up your registry, a pharmaceutical company might ask where in your country most of the patients are. There might be several reasons they are asking this and knowing why will help shape your approach. If they are at an early stage of R&D and designing a clinical trial, they might be trying to figure out which hospitals they should invite to be trial sites, so it would be important to know how far your users are from major cities. If they have already completed their trials and have recently had their product approved, they might be in the commercial launch phase and trying to figure out where to inform more doctors about their product. Each of these use cases has different data needs, privacy implications, and nuances of interpretation, which we will explore in more detail later.

As you develop your list, remember you are a stakeholder too, and for each question that your registry might answer, try and give an honest assessment; why do you want to answer this question? How will you act differently once you know the answer? What size of difference between groups might cause you to act differently? Who else will have to be convinced before you can make a decision? What would happen if you did not know the answer to a high degree of confidence; would a decision or action still be taken anyway? Too often we see registries set up that will only describe the state of a given population, with the intent of generating hypotheses that can be tested later. However, it is worth going through this exercise up front because in many cases the decisions you make at an early stage will become hard to change later on. If the data you gather have no path of becoming information needed to guide decisions, it is just being conducted for curiosity’s sake.

4 Technical Considerations

Early registries in the 1990s may once have been simple databases on the hard drive of a spare computer in a clinic. Today, most registries use cloud-based systems that allow for a greater degree of robustness against accidental data loss but also enable a variety of programs and services. For example, an academic clinical researcher might need a data dashboard that displays anonymous aggregate-level data to perform a statistical analysis. A patient might need a mobile app on their smartphone that collects questionnaires on a regular basis and syncs up with their smart watch. The non-profit running the registry may need a series of administrative tools that allow maintenance, software upgrades, or to set the permissions for other categories of user. Each of these users has a slightly different set of requirements and permissions to access or modify the registry data, but they also share some common requirements. They will have certain expectations that the software they use will be responsive, will work on a variety of devices (such as a tablet, smartphone, or desktop web browser), that it will be secure, and that it will conform with their local laws and regulations. Certain types of data, such as brain imaging files or whole genome sequencing data, can be very large and can only be usefully accessed with specialist software. A large amount of data can also be confusing (for any user) and might need to be contextualized by visualizing it as a chart or timeline of some type.

The most important users are the registry participants themselves and they will have their own needs and expectations. Depending on the condition they have, they are also likely to have a range of accessibility requirements such as adjustable font sizes, high-contrast modes for visual contrast issues, and compatibility with screen readers or assistive and augmentative communication devices [27]. For many conditions, it might be important for data from or about a patient to come from one or more caregivers, for example, one or more parents or other caregivers. While there is an increasing expectation that “there’s an app for that”, smartphone users risk being overwhelmed by the range of notifications, permissions, and settings that need to be managed when controlling their health data. There are also additional privacy concerns when their personal devices host sensitive health data when that device might be shared with other family members. Finally, there is a risk of widening the digital divide when relying only on the latest most expensive versions of hardware that are not available to all participants equally. Throughout the development of any registry, it is important to use a “human centered design” approach and continually gain feedback from the different stakeholders that will power your registry [28].

While a full discussion of registry technology is outside the scope of this article, there are a few high-level considerations to bear in mind (see Table 3). Broadly speaking, most registries are either bespoke (i.e., built just for you by a development team) or on a platform (i.e., a common core of generic features with some optional customization for your purposes from a menu of choices). While bespoke registries can be cheaper to develop initially and give more perceived control, there is a risk of being reliant on a very small team of individuals that know how it works and can make changes. Adding features like a mobile app or clinical trial modules could be too significant an undertaking for the team that originally built a simple web-based data collection tool, and there is a risk of the code becoming out of date as browsers and mobile devices evolve. If key individuals leave, the company closes, or there is a change of control, it might become more challenging to maintain control. Conversely, a platform-based registry may be more expensive upfront but will already cover some of the basic technical considerations and have a more intuitive user experience. They may also offer useful features that allow stakeholders to gain value from the registry much faster. In either case, there is a risk of “vendor lock-in” where it becomes harder to transfer your data and your community from one data environment to another in the event your needs change. A common complaint for either bespoke or platform-based registries is the presence of “bugs” and a months-long waiting period before the implementation of what seem like relatively small upgrade requests.

Table 3 Summary of approaches to registry development (non-exhaustive)
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5 Data Collection Considerations

You have probably noticed that various questionnaires you complete ask you about the same thing in different ways, whether it is the order in which you are asked for a date (e.g., DD/MM/YY vs MM/DD/YYYY) or whether you enter your height in inches or centimeters, everybody seems to do it a little differently. That is annoying in daily life, but it can be crucial when it comes to designing a patient registry. Unlike when you hand a piece of paper over to a human and they can check for errors and ask what exactly you meant (e.g., did you mean to write that you were “5 foot 9” where you have put “59 inches”?), online data entry is typically a one-shot process, so it has to be right the first time.

Even the way we ask users to enter things as simple as their age (or date of birth), sex (and/or gender identity), and location can become complicated very quickly. When it comes to entering dates about things that happened a long time ago many respondents will have to guess (hence a high proportion of dates entered as “January 1”). In general, the harder you make it to enter the right answer the more likely you will encounter errors in the data, or your participants will simply give up. While it can be appealing to consider the participants’ doctors entering data on their behalf, in practice this is almost impossible because of a lack of time in the brief clinical encounter or information technology security policy restrictions on hospital computers.

The method of data structuring becomes more critical as you consider with whom the data might be shared once they are collected. If you have a national registry then at some point you might want to compare your data with that from another country. If you think a researcher, a regulator, or a pharma company might want to look at your data, then its quality will be much higher if you enforce some data standards, i.e., guidelines by which data are described and recorded. You do not have to invent these yourself, there are existing standards like Logical Observational Identifier Names and Codes, which describe laboratory tests and their results, or International Classification of Diseases codes; however, these standards do not apply across all types of data that might be collected as part of a registry, and many rare diseases do not yet have an International Classification of Diseases code.

At a minimum, organizations should keep a record as to how data were collected and structured to allow for technical integration and/or further configuration down the road. If your registry has plenty of explanatory text on web pages or uses branching logic, it is best practice to build a “codebook” showing how the data are entered, validated, and what the user sees, preferably with screenshots, and to keep it updated as you make changes to data entry screens. That way if you change something on the website in the future, you can understand why you might be seeing changes or errors in the data. In our earlier example of height, perhaps we started out with an “open text box,” but then in a later version we made people choose to enter units as either centimeters or feet and inches. In a further iteration, we might decide to reduce the likelihood of out-of-range data by giving users a dropdown menu that only lists "feasible” heights (bearing a few unusual “edge cases” in mind, such as children, outliers at both ends, or even amputation).

If trying to merge or compare two or more different data sets, then considerable effort might go into “data harmonization,” i.e., deciding on which approach to prefer when comparing two datasets. A data scientist can help automate these rules so that you can compare those datasets more rapidly in the future, but it would be better to start with the same standards. In some conditions, an organization like the International Consortium of Health Outcomes Measurement or a consortium specific to your disease might have already done the work to define a “Core measure set” or “common data elements.” This can be a slow and deliberative process that takes place over several years though, so do not be surprised if nobody’s done that work yet in your field, but it is worth asking around because there may well be such a project underway.

One group created a comprehensive patient registry software systems checklist called CIPROS [29]. It may not be necessary to go into this level of detail when just starting out, but it could help structure the questions you want to ask of potential registry vendors as you work through your options. The European Cystic Fibrosis Society Patient Registry also published an extensive “lessons learnt” focusing on the collection, use, and improvement of data in their registry in an open-access publication [13].

6 Data Governance, Privacy, and Security

Data governance remains the cornerstone that enables patient registries to thrive. Typically, data are subject to the regulations of the country in which they are collected, with some countries requiring data collected about their citizens to be housed within that country. For those wishing to host a multi-national registry, there are some cloud-based solutions that allow you to specify a “hosting country”, or you might narrow eligibility to individuals in a specific country. Similarly, data collected about individuals who live in countries in which the European Union’s General Data Protection Regulation is in effect are beholden to the General Data Protection Regulation (in addition to local laws) regardless of the location of the organization collecting the data [30].

One regulation to be aware of when operating within the USA is the Health Insurance Portability and Accountability Act. The Health Insurance Portability and Accountability Act applies to the transfer of protected health information from one covered entity to another, i.e., health plans, healthcare clearing houses, and certain healthcare providers [31]. While the Health Insurance Portability and Accountability Act does not typically apply to a registry or a platform for which an individual shares their data, users may still have specific expectations with regard to the privacy and sharing rights applicable to their data.

Consent governs your permission to collect and store data, and to get in touch with your participants for the purposes of marketing, recontact, or invitation to a specific study. It may be efficient to try and secure ”broad consent” for all of these potential use cases when they first register to avoid needing to go back and “re-consent”. However, there is growing push back against consenting individuals in this manner [32], with a move towards “dynamic consent”, for which individuals are given more control over the use of their data on a case-by-case basis. The consequences of this more specific consent, however, will be more complex administration, reduced interoperability, and potentially lower sample sizes for specific studies.

Truly informed consent should ensure that each individual patient understands who the guardian of the data is and how decisions are made about access and use. Some patients’ groups may involve a third-party vendor (e.g., contract research organizations) that are for-profit entities that manage the risk of holding and analyzing or reporting on the data. This has value to ensure the smooth operations, processing, and ownership of data within a legal framework, but ultimately patient groups should remain the “data owner”. They should have transparent rules and processes in place specifying under which predetermined criteria that anonymized and aggregated data might be shared with third-party organizations such as clinicians and academics for research purposes, regulators and reimbursement agencies for drug evaluation purposes, and pharmaceutical or medical devices companies for drug/device development.

Anticipating these data scenarios will allow for careful consideration of the informed consent and commercial arrangements to be put in place. All such financial arrangements should be made publicly available in a “declaration of interest statement” that is kept up to date. One common approach to ensure good data governance is to create a “data access committee” that convenes several times a year and is responsible for evaluating each data request received. Such a committee should include key opinion leaders in the field to ensure the scientific value of each request, patient advocates to represent the needs of the patients, and independent methodologists. While US and European Union regulators are considering which regulations might enforce such best practice consistently, for the time being, a well-governed data control process remains paramount for maintaining the trust of the community.

Beyond focus on informed consent, running a patient registry will also require you follow laws and standard practices to ensure your data are stored securely. For example, the National Institute of Standards and Technology offers standards on implementing what is called Zero Trust as an architecture that considers potential risks of your registry data. These standards also support implementing workflows to ensure your organization is prepared and trained to protect sensitive health data of your registrants [33]. Furthermore, you will need to learn the basics of how to properly encrypt the database of your registry, and ensure there are clearly defined internal control policies to access the data in ways that honor the consent model entrusted by your registrants [34].

7 Building a Research Agenda

Before you develop a registry, it is useful to develop a research agenda. A simple heuristic is something we call “The Rumsfeld Research Agenda”. Based on a famous quote [35], the questions that are “knowns knowns” describe your sample and assess how it compares to the scientific literature. If you have a large and relatively unbiased method of recruiting participants, then we might find that the participants in your registry are very similar to those reported in the published scientific literature. For example, in an analysis comparing 10,255 members of the PatientsLikeMe multiple sclerosis registry with 4039 members of a specialist academic center database, the two samples were similar on age, age at onset, disease duration, gender ratio, family history, race, MS subtype, and even education level. However, owing to the large sample sizes, these were statistically significant differences and reflected the fact that PatientsLikeMe members were recruited via social media sites like Facebook, which tend to skew younger and more female [36]. While somewhat uninteresting that the data were fairly similar to another data source, this is an important cornerstone to understand any bias in the data you are collecting. If you were to skip this step and just start discovering “unknown unknowns” from the outset, then you would face inevitable questions of bias that might result from online methods [37].

Once you have established the representativeness of your sample, the next step is to study “known unknowns” [35]. A patient registry lowers the barriers to answer research questions that are obscure, under-researched, would be challenging to fund, or represent a long-standing gap in the literature. Within the PatientsLikeMe MS community, a survey on the impact of menopause in women with MS on their symptoms was able to quickly recruit N = 513 respondents and established that postmenopausal status, surgical menopause, and earlier age at menopause were associated with more severe symptoms [38]. The clinical-scientific collaborators on this study had been interested in the topic for many years but because it crossed multiple disciplines, was in the historically under-funded domain of women’s health, and had no direct impact on treatment, the study was otherwise challenging to conduct. This work has now been cited by other peer-reviewed articles over 40 times and informed several follow-up studies and systematic reviews. In this case, the “female bias” in the sample revealed by the earlier study was an advantage, not a limitation.

Finally, your registry can be a jumping-off point for hypothesis generation, innovation, and a rich foundry for “unknown unknowns” [35]. Registries have unexpectedly revealed that cancer drugs worked faster than the pharma company that made them noticed [39], been the launchpad for patient-led drug trials, [40] spawned dozens of offshoots in other countries [41], connected families to genetic counselors (e.g., https://www.duchenneregistry.org/), and become the basis for auditing the quality of care [42].

8 Commercialization and Sustainability

A registry can only be sustained if it generates revenue or secures larger donations. While grants have historically been a major funding source for starting registries, these are time limited. When the grant comes to an end, then either the data capture or maintenance of the registry comes to an end, or the work becomes reliant on the unpaid (and finite) good will of the host organization. Because this is a risky position, most funders now ask for sustainability plans through strategic partnerships such as with pharmaceutical and biotech partners (see Table 4).

Table 4 Summary of potential commercial approaches to sustainability (non-exhaustive)
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Registry costs to consider include staff time (i.e., management, product management, front end user interface, back end database development, quality assurance testing, infrastructure operations), platform maintenance and upkeep, recruitment support and initiatives, community moderation, marketing, and web hosting. This is without analysis and reporting costs, or efforts to publish and disseminate results. Therefore, there is no truly “free” service. There are, however, a variety of registry providers with various business models tailored to the organization. Some provide a free platform for advocacy organizations and use shared data ownership to help them recover the costs of maintaining the platform. Other platforms, like REDCap, charge organizations a small fee for long-term programs and for support services [43]. Still others charge organizations a licensing fee for use of the platform, but do not require shared data ownership. Depending on the organization’s needs, it may be possible to offset the licensing fees through data sharing or a similar agreement. At the time of writing, commercial providers of patient registries include (in alphabetical order and with no implied endorsement) Aparito, ArborMetrix, Clinical Pursuit, CorEvitas, IQVIA, Invitae, Luna, OM1, PatientsLikeMe, Pulse Infoframe, Sano Genetics, Syneos, and Thread Research, amongst others. There are also non-profit organizations such as the National Organization for Rare Disorders IAMRARE® registry program or the Rare-X data platform.

Another method organizations use to secure support for their work is to have a “corporate circle” or other membership scheme through which organizations solicit sponsorship from several relevant for-profit partners through which they maintain the registry. Examples include the American Association of Kidney Patients and NephCure Kidney. This method of sponsorship may be most relevant for organizations working in one or multiple conditions in which several pharmaceutical or biotech companies have an ongoing interest. Where there is only a single pharmaceutical sponsor responsible for funding, developing, and maintaining a registry, there is a risk that because of their interests and regulatory constraints that data will be restricted only to their products. In the longer term as more therapeutic options emerge, this may lead to a fragmentation of data. In addition, pharmaceutical companies can undergo many changes such as changes in therapeutic focus, the exhaustion of a patent, or corporate changes of control. Therefore, reliance on a single pharmaceutical sponsor presents an additional risk.

Aside from unrestricted financial support, many registries operate on a fee-for-service basis for more transactional services such as data access, advertising, academic research partnerships, and consulting services. It can be helpful to look at other resources in your space such as biobanks or other repositories and ask about their costing structure, which might include set-up fees, data licenses, and a variable fee depending on the number of participants, depth of data, and any additional support services needed billed out at an hourly rate.

Use caution and carefully evaluate the tools that you choose to run your registry. While some platforms use advertising revenue to support their platform, this can be problematic. While a simple business model, platforms may have little control over which ads they serve through an ad network, and the most common ads in the health space are either direct-to-consumer pharmaceutical ads (which may be restricted by global compliance regulations to certain territories) or may be for complementary and alternative medicine approaches with limited evidence of utility. The technology involved in targeting ads may also lead to greater privacy concerns for your users. As you evaluate which tools to use, consider how you negotiate with platforms to ensure the digital rights to data in your community are preserved. One such framework for evaluating and negotiating with platforms is provided by the Light Collective (https://lightcollective.org/trust/).

Many registries field surveys on behalf of academics, agencies, or pharmaceutical companies, and again it is important to consider the potential burden on your population, the potential for survey fatigue, and whether you will need to assist in the design, improvement, or implementation of a survey. Even a questionnaire assembled by clinical or research experts might benefit from patient expertise, which is a valuable service in itself. Where academics are writing grants, they may not yet have the funding in hand, but you should provide a quote to allocate to their budget. In general, a given grant has only a 5–10% chance of being accepted, so if the volume of such requests is becoming unmanageable it would be reasonable to either offer only a standard menu of service offerings or to charge for the time involved in making estimates. If pressed, researchers often do have access to patient and public involvement grants or may have discretionary research funds. After all, if 90% of the time your work supporting their grant writing will be in vain, then this may not be the best use of your time in the long term. Finally, there is the potential for generating revenue specifically by offering “consulting services” around engaging your community on behalf of your organization. Many nonprofit organizations give this away freely because they want sponsors to engage in their space, but in many cases, there are layers and layers of agencies, consultancies, data brokers, and advisors, all of whom are being paid. It would be illogical that those working (or volunteering) for a non-profit organization are the only agents in such activity not being paid for their contribution.

Some organizations have successfully built registries that facilitate paid participant engagement in clinical trials and/or market research, such as the COPD Foundation’s Patient-Powered Research Network [44]. Quality of engagement is valuable and should be reflected in the fees charged. Sponsors may wish to pay only for those potential participants that are randomized into a trial; however, many well-qualified leads you refer to them will either be rejected for inclusion/exclusion criteria beyond your control or may be lost to follow-up because of issues at the site like responding to enquiries in a timely manner [45]. Therefore, you might wish to structure access on the basis of a flat fee for a messaging campaign, or based on the number of message opens or “click throughs” rather than enrollments, which are beyond your control. This is also important because typically a sponsor will go to many recruitment sources all at once, and there may be duplicates in registrations across the vendors. For example, a potential trial enrollee “A” may be contacted through “ad agency X’s” e-mail campaign and then again through “hospital trial site Y’s” Facebook ad campaign, but then finally enrolls via your “non-profit registry Z.” So, who gets the credit, who can prove it, and who gets paid for participant A’s enrollment? Sometimes it is best to win this game by not playing it.

Finally, it is worth bearing in mind that commercial providers are charging above the level of mere cost recovery and that this is widely accepted practice. Ultimately, you cannot run your organization without resources, and you do not need to subsidize organizations who have endowments, revenues, and investors. If for some reason they lose interest in a few years’ time, you will still be here, so will your registry, and so will your (rising) costs. If you are good at something, never do it for free.

9 Privacy Risks

It is important to consider the very real risks of holding highly sensitive data. The trust of a community takes years to earn, minutes to lose, and can take years to rebuild. In this section, we discuss how to mitigate the risk of community data misuse.

We start with an example of how things can go wrong quickly. Since 2013, the non-profit organization Crisis Text Line has hosted a SMS text and social-media based suicide hotline for people in a mental health crisis to get help. Although the service provided support to millions of users, since 2017, a commercial partnership with the artificial intelligence spin-off company Loris.ai used anonymized datasets of over 200 million messages extracted from the service to optimize the performance of customer service chatbots. Critics questioned whether a 50-paragraph “terms of use” agreement merited proper consent from people in need of urgent help, and the organization’s own volunteers were unaware of the data repackaging [46]. To avoid similar issues yourself, it is worth using internal marketing campaigns, surveys, and user interviews to ensure there are “no surprises” with how data are being used.

Decisions beyond your control can incur privacy risks too. Technology platforms you adopt will inevitably want to test new business models, particularly in response to changing privacy policies or leadership, but these may not always benefit the community. For example, many advocacy organizations created Facebook Groups to provide social support, reach an audience, and to grow their communities [47]. However, because such tools prioritize “engagement” they may inadvertently reveal personal information by disclosing membership of a sensitive group such as being a carrier for a disease-associated genetic variant. Their engagement algorithms may also inadvertently promote misinformation [47]. While mainstream social media platforms can support fundraising, connection, and advocacy, they were not built with the same intent or constraints as true registries.

Consider the privacy issues that you create for your community over the long term. Many new or emerging registry tools may appear to be an “easy fix,” to reach your community. However the lack of rights to your collective data may quickly sow mistrust and even cause real harm, as shown by patient groups who tried to emerge from using Facebook as a lightweight registry [48]. Consider how a third-party platform may target ads to your community or resell your community’s data [49], and consider how sensitive data about your community can be leaked to third parties or data brokers [50].

Regularly put yourself in the shoes of someone joining your registry today. Data have the potential to heal, but it also holds the power to cause harm when in the wrong hands. With great power comes great responsibility. You will need to understand how to make sure the technology and tools you use to implement your strategy are worthy of your trust, and the trust of your community. Consider your rights to the data as you adopt any new technology, and if you are uncertain, it is usually worth investing in legal counsel to help you understand your country’s health data privacy and compliance laws. There are additional potential risks to consider presented in Table 5 along with ways to mitigate them.

Table 5 Risks and mitigation strategies
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10 Conclusions

For someone just starting their journey on developing a patient registry, this brief (but broad) education article may appear daunting. There is certainly the potential for greater depth and complexity behind any of the topics we have covered including data, research agendas, governance, privacy, sustainability, and mitigating the types of challenges that may appear, and we would encourage interested readers to explore the references provided. Fortunately, this is now a well-worn path and you do not have to create every aspect of your registry from a blank slate. Increasingly, there are now a range of developers and software providers who can get you started much quicker than in the past, though continuity and interoperability must always be primary considerations when partnering with another organization.

Table 6 details additional resources you can explore in greater depth and use as a starting point for developing your own registry, but the most practical advice can always be found by connecting to other people who have built their own registry in adjacent areas. It might be another pediatric indication like yours, or a different form of cancer, or someone who has developed a registry around a similar drug or device that might apply in your condition but for a different indication. Because technologies, regulation, and funding opportunities are so dynamic, it is important to connect with those who have launched their own registries recently, ideally in the same territory.

Table 6 Further resources
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We leave the closing words to someone sharing their lived experience, first as someone who has been through this journey and emerged successfully on the other side (author SF, Electronic Supplementary Material), and finally from a participant themselves: “The register means a huge deal to me, as a parent … it would be so incredible to have this data coming from our community that we can then take to the (health service), to the professions, to the organizations and say “this is what we know to be true about this condition”.