Empowering Patients and Researchers through a Common Health Information Registry: A Case Example of Adrenocortical Carcinoma Patients and Researchers
Deborah ALLWES1, BSN, RN, MPH and Michael L. POPOVICH, MS2 1 Senior Public Health Specialist, Deborah_Allwes@stchome.com 2CEO, Michael_Popovich@stchome.com
Scientific Technologies Corporation, 4400 E. Broadway, Suite 705, Tucson, Arizona 85711, + 520.202.3333
Abstract: Adrenocortical Carcinoma is a rare malignant tumor that forms in the outer layer of tissue of the adrenal gland, which is a small gland situated on the anteriosuperior aspect of the kidneys. These glands produce steroid hormones, adrenaline, and noradrenaline that control heart rate, blood pressure, and other body functions.
Because this cancer affects a limited number of patients, it is referred to as an Orphan disease, which is defined as a condition that affects fewer than 200,000 people nationwide. Internationally, there are 5,000 - 8,000 such diseases affecting an estimated 55 million people. There is often limited medical intervention for many of these conditions.
With a small number of patients, and a correspondingly small number of providers and researches, this disease is a candidate for establishing a sharable information system that is used by the patient, provider, and researcher. This resource empowers the patient to support their care and treatment while allowing medical providers and researches to have valuable and broad access to patient activities and behaviors that may impact their treatment.
Orphan disease registries are prime candidates for establishing health information resources that support communications between patients, providers, and researchers. As a resource, this information can be used to facilitate treatment protocols to include biomarker identification, testing and monitoring of new drugs. By empowering a common community of individuals that share a common disease, the potential to accelerate research and identify improved treatment options may also increase.
This paper presents a strategic plan and design for implementing Orphan disease registries within an e-health environment that specifically links patients and providers with researchers. The Adrenocortical Carcinoma Registry will be used to demonstrate the implementation and potential of these systems.
1. Background
Disease has been an expected part of human life throughout history. Notable infectious diseases, such as influenza and poliomyelitis affect a large number of populations, and therefore receive a large amount of funding and research for treatment. Emergent diseases in the 20th and 21st Centuries, such as the Human Immunodeficiency Virus (HIV) and the Severe Acute Respiratory Syndrome (SARS) seemingly draw international attention for their rapid spread and widespread reach. Other diseases, such as cancer, are found throughout the world and collectively affect a large number of people. However, although cancer is referred to as a single disease, in actuality, cancer consists of over 100 different forms of the disease. The subsets of cancers differ based on many factors such as geography, age, and genetics. Because each subset of cancer, specifically, each type of cancer, potentially affects a small number of people within a given population, often the time, money, and data to support research, and consequently, treatments for such cancers is lacking or nonexistent.
1.1. Orphan Disease Overview
Some types of cancer, as with many types of diseases affecting a small number of people within a population, are classified under Orphan Diseases. In the United States, these orphan diseases, or rare diseases, affect less than 200,000 people. Generally, an orphan disease is one that has a low prevalence, usually a prevalence of less than 5 cases per 10,000 in a given population. Internationally, there are over 5,000 such diseases affecting an estimated 55 million people.
While some orphan diseases, such as Cystic Fibrosis, have been researched and funded to allow for a greater understanding of the disease, most orphan diseases have not. Patients are often left to collect information and understanding of their condition on their own with limited resources. Their providers, which often lack an in-depth understanding of the disease, have to seek out information based on limited research. Finally, the researchers that dedicate time and attention to the orphan disease often do so with very limited financial incentives and lack of a collective data repository.
1.1.1. Adrenocortical Carcinoma: A Case Study of an Orphan Disease
Internationally, of the over 5,000 orphan diseases, only approximately 1,300 have been well studied from a medical perspective1. The remaining orphan diseases have yet to be thoroughly studied and medically understood. In the United States, malignant neoplasm’s of the adrenal cortex, such as Adrenocortical Carcinoma (ACC) account for only 0.05% - 0.2% of all cancers2.
Adrenocortical Carcinoma is a rare malignant tumor that forms in the outer layer of tissue of the adrenal gland, which is a small gland situated on the anteriosuperior
Weely, S., Leufkens, H., Priority Medicines for Europe and the World “A Public Health Approach to Innovation”, Background Paper, Orphan Disease, 7 October 2004.
2 Latronico, A., Chrousos, G., Extensive Personal Experience, Adrenocortical Tumors, Journal of Endocrinology and Metabolism, Vol. 82, No 5, p. 1317, 1997.
aspect of the kidneys. These glands produce steroid hormones, adrenaline, and noradrenaline that control heart rate, blood pressure, and other body functions.
ACC has a bimodal age distribution with the first occurrence noted in children and the second occurrence noted in the 3rd, 4th, or 5th decades of life. Although the number of individuals actually inflicted with this cancer is small, its impact is dramatic. The prognosis of ACC is poor, and the survival rate is minimal.
Resources for patients with ACC are scarce, and even scarcer are the medical, historical, and epidemiological data available to researchers. There is no centralized repository that promotes patients to interact. Likewise, there is no centralized database for researchers to query medical information. Consequently, patients have objective and subjective case information that is not privy to the researchers that are attempting to develop treatments for the disease. ACC patients, like many orphan disease patients, are a wealth of information that can provide valuable information on an individual level, and collectively as a group.
Figure 1 represents the current state of information within the ACC patient, medical, and research community.
Locally in patient’s hard chart
Presents to
Case information is documented
Data is collected
Stored
Stored
Patient
Provider
Locally in patient’s electronic chart
Provider A
Provider knowledge is not shared
Data is not shared
Locally in patient’s hard chart
Case information is documented
Data is collected
Stored
Presents to
Stored
Researchers draw on patient and provider data from disparate sources
Patient
Provider
Locally in patient’s electronic chart
Provider B
Provider knowledge is not shared
Data is not shared
Locally in patient’s hard chart
Presents to
Case information is documented
Data is collected
Stored
Stored
Patient
Provider
Locally in patient’s electronic chart
Provider C
Patients are not readily able to find a collective source of information and patients rarely have the ability to exchange archived or real-time information. A new ACC case often presents less than one case per year of a provider’s total workload, so knowledge and information for providers is often dependent on the provider’s own experience, or research. Because of a lack of a collective data source, researchers have to retrieve data from many disparate sources, leading to time delays and financial burdens.
2. Benefits of a Shared Resource
The benefits to having a shared resource, such as an orphan disease registry application, are immense. In Figure 2, it is demonstrated how patients can interact with each other, either through real-time on-line chat rooms or through archived information. This is a very important aspect to the registry application as it empowers the patients to have control over their disease, as well as allows them to have an active input into their medical case and overall body of knowledge of their disease. Patients can participate in questionnaires and on-line forums that will promote researchers to have a better understanding of the effects a treatment is having on patients as it is happening.
Patients exchange archived and real-time data
Provider
Provider
Patient
Patients exchange archived and real-time data
Data can be entered through a secured, encrypted web-based application that allows for scanned documents, images, and connection to outside registries and other applications such as pathology repositories and laboratory systems.
Providers enter historical and case data And query data
Patient
Orphan Disease Registry Database
Patient
Patients exchange archived and real-time data
Patients exchange archived and real-time data
Researchers draw on patient and provider data from singular database
Patient
Researchers have a direct benefit of having all of the data and information of ACC in one secured location. They can extract data through scheduled reports, ad hoc reports, or through extracting the information into SAS, SPSS, Microsoft Access, or other statistical packages. Because patients will have the ability to upload scanned documents into the database, researchers can have access to numerous possibilities of information that they would otherwise not be able to collect. Additionally, researchers can use complex analysis of translational biomarkers and molecular profiling for improved drug therapies and earlier diagnostic testing.
Providers have the benefit of viewing on-line laboratory and pathological information from the database, as well as are able to view what other providers are noting with their patients, and treatment plans.
2.1. Pharmaceutical Industry Benefits
An Orphan Disease Registry Application can provide a common place for the ACC community, and eventually other orphan disease communities, to collaborate, compile, exchange, and analyze information related to generalized disease processes and drug development. Commercial partnerships can be developed to enhance and support this effort, helping to establish links currently missing in overall orphan disease drug development, including those for ACC. Additionally, this collaborative effort can provide the foundation for scientists lacking development expertise and commercial outlets for orphan drug development, testing, commercialization, and marketing.
3. Registry Design for Adrenocortical Carcinoma Case Study
The registry design for ACC, and for all orphan diseases, has to be flexible enough to adapt to evolving disease bodies of knowledge, secure enough to allow patients to know their data is safe, and accessible enough for researchers and providers to query the information they need. Overall, such as design needs to allow for future expansion while allowing for current disease specific information exchange.
3.1. Technical Overview of the Registry
Specific to the ACC Orphan Disease Registry Application, the following criteria must be met. In addition to the criteria is a brief description of the “tools” that should be utilized to measure each criterion.
· Data entry process: a data entry process should be established. Data from standard forms should be entered into a web based application/repository. Validations and quality checks should be in place to ensure quality of data.
· Standardization: the system should be configured based on accepted standards as defined by clinical data interchange standards consortium (CDISC), health level seven (HL7), and any other designated vocabulary standards.
· Reporting: a reporting mechanism should be in place and should provide consistent and ad hoc reports as defined by researchers.
· Hardware/environment configuration: required hardware should be procured, and configured (if required) to enable solution delivery.
· Access to patient data: providers, researchers, patients, and other authorized users should have online access to patient data via a secure internet site. All patient data should be de-identified, and should follow all security standards, and internal review board (IRB) recommendations, as applicable.
· Scanner interface: provide a scanner interface to the orphan disease registry application, to upload and retrieve scanned documents.
· Help desk: provide data entry and help line.
. Training and user manual: provide user training and user help documentation.
Table 1 is a representation of the hardware/software specifications that should be included in any orphan disease registry application, specifically that of the ACC.
| Hardware/Software | QTY | Minimum Requirements |
|---|---|---|
| Hardware | ||
| PowerEdge 2950 (Database Server) | 2 | Processor: Dual Core Intel Xeon 5160, 4MB Cache, 3.00GHz |
| Memory: 8GB 533MHZ (4x2GB Dual Ranked) | ||
| OS: Windows Server 2003 R2 Enterprise Edition | ||
| Hard Drive: 146GB (x5) 15k RPM - RAID 5/i | ||
| Power: Redundant Power Supply with Y cord | ||
| Riser Card with 3 PCIe Slots | ||
| 1x6 Backplane for 3.5-inch Hard Drives | ||
| Controller: PERC 5/I, x6 Backplane Integrated Controller Card | ||
| Rack Chassis w/Sliding Rapid/Versa Rails | ||
| Dual Embeded Broadcom NetXtreme II gigabit card | ||
| 3 YR Gold Enterprise Support | ||
| 24X IDE CD-ROM Driver | ||
| Mouse/Keyboard | ||
| PowerEdge 2950 (Application Server) | 4 | Processor: Dual Core Intel Xeon 5160, 4MB Cache, 3.00GHz |
| Memory: 4GB 533MHZ (4x1 Dual Ranked) | ||
| OS: Windows Server 2003 R2 Standard Edition | ||
| Hard Drive: 36GB (x4) 15k RPM - RAID 5/i | ||
| Power: Redundant Power Supply with Y cord | ||
| Riser Card with 3 PCIe Slots | ||
| 1x6 Backplane for 3.5-inch Hard Drives | ||
| Controller: PERC 5/I, x6 Backplane Integrated Controller Card | ||
| Rack Chassis w/Sliding Rapid/Versa Rails | ||
| Dual Embeded Broadcom NetXtreme II gigabit card | ||
| 3 YR Gold Enterprise Support | ||
| 24X IDE CD-ROM Driver | ||
| Mouse/Keyboard |
| Hardware/Software | QTY | Minimum Requirements |
|---|---|---|
| Software | ||
| Oracle 10g Standard One | 2 | |
| WebSphere 6 Application Server | ||
| 4 |
Primary
Production Application Server Dual Core Xeon 3.0GHz 4GB Memory
Test/Training Application Server Dual Core Xeon 3.0GHz 4GB Memory
Windows 2003 Standard WebSphere 6
Windows 2003 Standard WebSphere 6
Database Server Dual Core Xeon 3.0GHz 8GB Memory
Windows 2003 Enterprise Edition Oracle 10g Standard One
Backup
Production Application Server Dual Core Xeon 3.0GHZ 4GB Memory
Test/Training Application Server Dual Core Xeon 3.0GHZ 4GB Memory
Windows 2003 Standard WebSphere 6
Windows 2003 Standard WebSphere 6
Database Server Dual Core Xeon 3.0GHZ 8GB Memory
Windows 2003 Enterprise Edition Oracle 10g Standard One
A gap analysis will be desirable to ensure that the information that is truly needed to be included in the orphan disease registry application is actually identified and included. Table 2 is an example of a gap analysis matrix.
| Gap # | Gap/Current State Description | System Requirement # | Gap Resolution/Desired State Description |
|---|---|---|---|
| 1.00 | Disease forms are physically stored in provider offices and providers/patients/researchers currently don't have access to these collective forms | The system must be a web-based application | Online based forms will be established to collect and route the ACC forms from a provider/patient/researcher to a centralized location/database |
| 2.00 | Currently there is no electronic tracking of collective ACC data, providers/patients/researchers and other users do not have access to the ACC patient data | The application must have a centralized database | Data from ACC forms will be entered into the Orphan Disease Registry Application for electronic tracking and will be available to authorized users |
| 3.00 | Currently there is no validation of provider stored data | To be identified | Incorporate validations required by researchers |
| 4.00 | There is no ability to store scanned documents in a centralized location/database | They application must allow for scanning and uploading documents | Orphan Disease Registry Application will have the ability to store and retrieve scanned images |
| 5.00 | Currently there is no accepted standards for messaging language | The application must be standards based | Standards will be used in the vocabulary for the Orphan Disease Registry Application |
3.2. Example of a Form from the ACC Case Study
The application that is built for an orphan disease registry, such as the one for ACC, is that it is user-friendly. System administrators will need to be able to add, view, edit, and retrieve standard and customized forms. The forms will likely change as time progresses and researchers identify areas of interest for further study. Consequently, the application will need to allow not only the editing and storage of current forms, but archived forms as well. Figure 4 is an example of a partial ACC form that may be used in the application.
1) What is your age?
2) What is your gender? ☐ Male
☐ Female
3) What is your race? (Please check all that apply) ☐ White
☐
American Indian/Alaska Native
☐ Asian
☐ Native Hawaiian or Other Pacific Islander Black or African American ☐
4) Are you Hispanic or Latino? ☐ Yes
☐ No
5) When were you diagnosed with adrenocortical cancer (mm/yy)?
6) How was the diagnosis made? (Please check all that apply) ☐ ☐ ☐ ☐ ☐ ☐ Tumor biopsy Tumor/adrenal gland removal Imaging tests such as a CT or MRI scan Blood tests Urine tests Other, please specify:
7) What symptoms did you experience before being diagnosed? (Please check all that apply) ☐ None
☐
Abdominal pain, date of onset:
☐
Palpable abdominal mass, date of onset:
☐
Purple lines on abdomen (abdominal purple striae), date of onset:
Acne, date of onset: Loss of appetite (anorexia), date of onset: Weight loss greater than 10 pounds Weight gain greater than 10 pounds Excessive accumulation and storage of fat in the central area of the body (central obesity), date of ☐ ☐ ☐ ☐ ☐ onset: ☐
Cramps, date of onset: specify cramps, e.g leg or stomach cramps?
☐
Decreased libido, date of onset:
☐
Emotionally unstable (emotional lability), date of onset:
☐
Excess blood in the face marked by reddish complexion and swelling (facial plethora), date of onset: Fatigue, date of onset:
☐
☐ Fungal skin infections, date of onset:
45
☐ Headaches, date of onset:
☐
Excessive growth of hair of normal or abnormal distribution (hirsutism), date of onset:
☐
High blood pressure (hypertension), date of onset:
☐
Increased abdominal girth, date of onset:
☐ Muscle weakness in upper legs/thighs (proximal muscle weakness), date of onset:
☐ Muscle weakness, date of onset:
☐
Nausea, date of onset:
Kidney stone(s), date of onset: Excessive or abnormal thirst (polydipsia), date of onset: Excessive urination (polyuria), date of onset: ☐ ☐
☐
If yes, frequency of urination is; ☐
once per 1 hour once per 2 hours once per half hour Other, please specify:
☐
☐
☐
date of onset:
If female:
☐
Deepened voice, date of onset:
☐
Irregular menstruation, date of onset:
If male:
☐
Impotence, date of onset:
8) Have you had a bone scan with abnormal results (for example, evidence of loss in bone volume or mass)? ☐
Yes, date of most recent scan:
☐ No
4. Recommendations for Other Orphan Disease Registries
Orphan diseases, when considered individually, are limited by the size of the populations affected and the limited number of cases. Collectively, however, there is an estimated 55 million people affected by one of the 5,000 - 8,000 orphan diseases. As is often the case, there is power in numbers. ACC, in and of itself, doesn’t have the large numbers of affected individuals to be sway policy and industry to stop and take notice. However, if taken in whole with the rest of the orphan diseases, there is a strength that all orphan diseases can draw from. Disease processes can be explored for generalization, drug development can be based on the uniqueness of orphan diseases, and patient participation can be capitalized through a common area of shared knowledge.
Many orphan disease registry options can exist. Registries can be built for individual orphan diseases, but are then limited by the lack of ability to draw from all orphan disease processes. By incorporating most orphan diseases, or at least orphan diseases based on commonalities, researchers are not limited to only one set of data and can find common ground among different orphan diseases, thus expanding knowledge and understanding of all orphan diseases.