An automated communication system in a contact registry for persons with rare diseases: Scalable tools for identifying and recruiting clinical research participants

https://doi.org/10.1016/j.cct.2008.09.002Get rights and content

Abstract

Objectives

Strategies for study recruitment are useful in clinical research network settings. We describe a registry of individuals who have self-identified with one of a multiplicity of rare diseases, and who express a willingness to be contacted regarding possible enrollment in clinical research studies. We evaluate this registry and supporting tools in terms of registry enrollment and impact on participation rates in advertised clinical research studies.

Methods

A web-based automated system generates periodic and customized communications to notify registrants of relevant studies in the NIH Rare Diseases Clinical Research Network (RDCRN). The majority of these communications are sent by email. We compare the characteristics of those enrolled in the registry to the characteristics of participants enrolled in sampled RDCRN studies in order to estimate the impact of the registry on study participation in the network.

Results

The registry currently contains over 4000 registrants, representing 40 rare diseases. Estimates of study participation range from 6–27% for all enrollees. Study participation rates for some disease areas are over 40% when considering only contact registry enrollees who live within 100 mi of a clinical research study site.

Conclusions

Automated notifications can facilitate consistent, customized, and timely communication of relevant protocol information to potential research subjects. Our registry and supporting communication tools demonstrate a significant positive impact on study participation rates in our network. The use of the internet and automated notifications make the system scalable to support many protocols and registrants.

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

References (57)

  • L. Aitken et al.

    Principles of recruitment and retention in clinical trials

    Int J Nurs Pract

    (2003)
  • Rare Diseases Act of 2002. [Page 116 STAT. 1988] Public Law 107-280. 107th Congress,...
  • PEC

    Rare Disease Clinical Research Network Public Website, Pediatrics Epidemiology Center

    (2006)
  • D.M. Parkin

    The evolution of the population-based cancer registry

    Nat Rev

    (2006)
  • A.M. Montano

    International Morquio A Registry: clinical manifestation and natural course of Morquio A disease

    J Inherit Metab Dis

    (2007)
  • C.M. Eng

    Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry

    J Inherit Metab Dis

    (2007)
  • A.E. Tattersfield et al.

    Lymphangioleiomyomatosis: a national registry for a rare disease

    Am J Respir Crit Care Med

    (2006)
  • T. Hampton

    Parkinson disease registry launched

    JAMA

    (2005)
  • B. Berger

    The prevalence of diabetes in a Swedish population of 280,411 inhabitants. A report from the Skaraborg Diabetes Registry

    Diabetes Care

    (1998)
  • B. Berger et al.

    Incidence, prevalence, and mortality of diabetes in a large population. A report from the Skaraborg Diabetes Registry

    Diabetes Care

    (1999)
  • J. Brown et al.

    Impact on a population-based registry of changing diagnostic thresholds for diabetes

    Diabetes Care

    (1998)
  • G. Bruno

    Incidence of type 1 and type 2 diabetes in adults aged 30–49 years: the population-based registry in the province of Turin, Italy

    Diabetes Care

    (2005)
  • G.L. Nielsen

    Analyses of data quality in registries concerning diabetes mellitus—a comparison between a population based hospital discharge and an insulin prescription registry

    J Med Syst

    (1996)
  • M. Palta

    Longitudinal patterns of glycemic control and diabetes care from diagnosis in a population-based cohort with type 1 diabetes. The Wisconsin Diabetes Registry

    Am J Epidemiol

    (1996)
  • M.T. Tenconi

    The incidence of insulin-dependent diabetes mellitus: preliminary data from an organized population registry in Pavia Province

    Epidemiol Prev

    (1991)
  • A. Bossi

    What is the incidence of cystic fibrosis in Italy? Data from the National Registry (1988–2001)

    Hum Biol

    (2004)
  • L. Viviani

    The Italian registry for cystic fibrosis: what has changed in the last decade

    Epidemiol Prev

    (2003)
  • S.S. Wang

    Early diagnosis of cystic fibrosis in the newborn period and risk of Pseudomonas aeruginosa acquisition in the first 10 years of life: a registry-based longitudinal study

    Pediatrics

    (2001)
  • Cited by (28)

    • Engaging Participants in Rare Disease Research: A Qualitative Study of Duchenne Muscular Dystrophy

      2016, Clinical Therapeutics
      Citation 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 Trials
      Citation 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.

    • The Rare Diseases Clinical Research Network Contact Registry update: Features and functionality

      2012, Contemporary Clinical Trials
      Citation 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].

    View all citing articles on Scopus

    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.

    View full text