An automated communication system in a contact registry for persons with rare diseases: Scalable tools for identifying and recruiting clinical research participants☆
Introduction
Obtaining sufficient numbers of participants to meet study objectives has always been a challenge for clinical research and is a particular problem for rare diseases [1], [2]. Diseases or conditions that affect < 200,000 persons in the United States are considered rare diseases under the Rare Diseases Act of 2002 [3]. Because of the low prevalence of these conditions, the identification of sufficient numbers of research subjects is also a big challenge. The Rare Diseases Clinical Research Network (RDCRN) coordinates research studies on over 50 rare diseases [1], [4]. The network consists of ten clinical research consortia, each focused on a group of related rare diseases. A centralized Data and Technology Coordinating Center (DTCC), located at the University of South Florida (USF) College of Medicine, has developed and maintains an administrative disease registry to help identify potential research subjects for the RDCRN network studies. Our registry system collects only contact information, self-reported diagnosis, and demographic information. A web-based system supports the electronic collection of contact information and provides automated communications with individuals who self-identify with a rare disease and express interest in clinical research participation. The automated Contact Registry we describe is scalable to support many studies, thereby sustaining a pool of possibly eligible participants for clinical protocols on a spectrum of rare diseases. Here we describe the system and present early evaluation using study participation rates as an outcome measure.
Disease registries—controlled lists of persons with a specified clinical condition, and their associated data—are used to support public health and clinical research activities. Such registries have been used in cancer research since the 1940s as tools to estimate cancer incidence and support etiological exploration by recording cases reported within a defined time or place [5]. Disease registries can be characterized by their purpose. Administrative registries are used to identify patients with particular conditions, usually for later epidemiological study. Population-based registries collect disease-related data (either from self-report or from medical records after patient consent) that is later used for data-mining, hypothesis generation, and secondary research questions. More recently, genetic registries (those that identify individuals with a given genetic mutation or profile) are becoming more frequent for recruiting and follow-up of relatives of affected individuals [6], [7]. Registries of all types have been used to support research of rare diseases such as Mucopolysaccharidosis Type I (MPS I) [6], [7], Fabry Disease [8], Lymphangioleiomyomatosis [9], and Parkinson's disease [10]. For more prevalent conditions, such as diabetes, multiple registries might exist for a single disease [11], [12], [13], [14], [15], [16], [17]. In addition to identifying persons afflicted with diseases or conditions, registries can be used to ascertain recipients of procedures and devices. For example, the New Approaches to Coronary Intervention (NACI) registry is funded by the National Heart, Lung, and Blood Institute (NHLBI) to track outcomes of new coronary interventional devices [18], and INTERMACS is a national registry for patients who are receiving mechanical circulatory support device therapy to treat advanced heart failure [19].
Disease registries have long been used to assist the clinical research process. Registries have been used to estimate achievable sample size for prospective clinical trials [20] and to explore research questions on incidence [21], [22], screening [23], [24], growth rates [23], [25], co-morbidities [26], [27], [28], [29], and mortality [23], [30], [31], [32] in hundreds of diseases, including heart disease [33] and cystic fibrosis (in multiple countries) [26], [30], [32], [34], [35], [36].
A major challenge in clinical trials is identifying potential research subjects. The notion of maintaining lists of affected individuals who express interest in participating in clinical research trials as a “pool” of potential research subjects is an appealing prospect for researchers, who often are forced to advertise for research participation. Cultivated and managed lists of possibly eligible and interested research subjects simplify study recruitment and perhaps increase the likelihood of complete trial accruals. Registries have been used in this way to identify and recruit patients for clinical research studies [37], [38], [39], [40]. The National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members collects information from affected individuals (and their unaffected family members who elect to join) and matches them with scientists who are looking for subjects to participate in research trials [41]. Affected individuals join the registry to receive personal notification of research projects they may be eligible to participate in, and researchers can approach the registry for assistance recruiting people to participate in their studies [39].
The protection of confidentiality and assurance of meaningful informed consent are important issues when recruiting patients for clinical research from disease registries [42], although several studies imply that potential research subjects appreciate direct communication of clinical research information. A survey of policies for research contact with patients registered in cancer registries revealed that the strategy used most frequently (among those registries that allowed patient contact) was for investigators to contact patients after notification of their physician, rather than more restrictive policies requiring registry staff to obtain physician permission to contact patients [43]. A comparison of these two strategies for study recruitment (direct contact by research staff and contact by research staff after physicians alert potential participants) from a cancer registry found no difference in study participation rates [42]. Authors concluded that although there are confidentiality concerns when recruiting research participants from disease registries, the notification of physician might create pressure for participation. A separate survey of 100 registrants in another cancer registry found that the majority of patients said they preferred that researchers contact them directly about their interest in research participation, rather than checking with their physician first [44]. Among those respondents who wanted their physician involved, most preferred a physician notification rather than a physician permission approach [44]. Each of these studies emphasized the need for registry enrollees to be clearly informed about how the registry will be used for research.
The internet has created virtual communities for affected individuals and opportunities for education for disease management, treatment and research information, advocacy, and social support. The use of the internet to support recruitment of participants has been successful in other research contexts [45], [46]. In addition, the use of the internet to support the enrollment and communication with individuals enrolled in administrative registries, such as the RDCRN Contact Registry, show potential to link with the increasing number of online and electronic clinical trial registries [47], [48], [49], [50], [51], [52].
Section snippets
Overview
The information collected by the RDCRN Contact Registry is used by the DTCC to identify potential study participants (by diagnosis, age, gender, and/or geography) and to send customized information regarding open or planned clinical studies on behalf of RDCRN investigators. The DTCC does not share any identifying information from contact registrants with RDCRN investigators. Rather, RDCRN investigators use the DTCC to send consortium and protocol-specific information to potential research
Utilization
The RDCRN consists of ten clinical research consortia categorized by disease types. As of November 2007, over 4000 individuals representing over 40 different rare diseases from 61 different countries were enrolled in the RDCRN Contact Registry: Angelman, Rett, and Prader–Willi (ARP: n = 623); Bone Marrow Failure (BMF: n = 326); Cholestatic Liver Disease (CLIC: n = 230); Neurologic Channelopathies (CINCH: n = 108); Genetic Diseases of Mucociliary Clearance (MCC: n = 233); Genetic Steroid Disorders (GSD: n =
Limitations
Without a direct link between individuals on study (for which the DTCC has only de-identified information) and those in the Contact Registry, it is impossible to know for sure whether we have matched individuals correctly. However, since the sampled RDCRN studies target rare diseases, the likelihood that two individuals on a given study happen to have the same birth date is presumably very low. In fact, we did not find the same birth date between any two individuals among the subjects whose
Conclusion
The RDCRN Contact Registry offers a means to accumulate potential study participants for network studies. The automated communication system provides rapid, economical, and scalable methods for Contact Registry maintenance. The registry can be a resource of potentially eligible and interested subjects and can increase efficiency of clinical trial recruitment. In the diseases under study in the RDCRN, the Contact Registry has contributed a proportion of participants to clinical research
Acknowledgments
The project described was funded by Grant Number RR019259 from the NCRR, an NIH component, and the Office of Rare Diseases. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or ORD or the NIH. The authors are grateful to the members of the RDCRN Coalition of Patient Advocacy Groups (CPAG) and the RDCRN Steering Committee for their influence on the design and operations of this registry. We also express gratitude to Jamie
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Engaging Participants in Rare Disease Research: A Qualitative Study of Duchenne Muscular Dystrophy
2016, Clinical TherapeuticsCitation Excerpt :The approach of using registries for recruitment requires individuals to log on to a website and provide their (child’s) medical history, typically without any contact with clinical staff. This passive strategy may be ideal for highly motivated or informed volunteers who are specifically interested in research; however, this method does not diversify the population base.32 Although patient registries such as DuchenneConnect have been useful for notifying patients of research opportunities, the utilization of registries was not consistently referenced by parents.
Using registries to recruit subjects for clinical trials
2015, Contemporary Clinical TrialsCitation Excerpt :If recruiting subjects for clinical trials in high prevalence diseases is challenging, recruiting subjects for clinical trials in rare diseases (fewer than 200,000 people with the disease in the US) is much more challenging. Recognizing this, the NIH supported the development of the Rare Disease Clinical Research Network (RDCRN) Contact Registry in 2004 (37). Initially it included 40 rare diseases.
Respiratory diseases registries in the national registry of rare diseases
2014, Archivos de BronconeumologiaThe Rare Diseases Clinical Research Network Contact Registry update: Features and functionality
2012, Contemporary Clinical TrialsCitation Excerpt :In 2007, we presented our approach for enhancing enrollment in rare disease studies using a Contact Registry for the Rare Diseases Clinical Research Network (RDCRN) [1].
Direct-to-Consumer Recruitment Methods via Traditional and Social Media to Aid in Research Accrual for Clinical Trials for Rare Diseases: Comparative Analysis Study
2023, Journal of Medical Internet Research
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Grant support: The project described was funded by Grant Number RR019259 from the NCRR, an NIH component, and the Office of Rare Diseases. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or ORD or NIH.