WO2001095059A2

WO2001095059A2 - A method and system for populating a database

Info

Publication number: WO2001095059A2
Application number: PCT/US2001/018067
Authority: WO
Inventors: Hugh Young Rienhoff, Jr.; James Robert Kean; Hywel B. Jones; John Sotos
Original assignee: Dna Sciences, Inc.
Priority date: 2000-06-06
Filing date: 2001-06-04
Publication date: 2001-12-13
Also published as: AU2001275213A1; WO2001095059A3

Abstract

Systems and methods for populating a secured database for further medical characterization through a worldwide network of computers. The method includes providing a server 207 coupled with a worldwide network of computers 210, and providing a website configured to create trust of the website by users. The method also includes providing medical questionnaires on the website to obtain information from a user, and analyzing the information obtained from the user to determine whether to invite the user to submit a biological tissue sample. The method further includes inviting a user 201 to submit a biological tissue sample, and transmitting from the server to the user instructions for submitting a biological tissue sample. The method additionally includes receiving a biological tissue sample from the user, and analyzing the biological tissue sample to obtain genetic information. The method still further includes populating the secured database with the genetic information 215.

Description

A METHOD AND SYSTEM FOR POPULATING A DATABASE

CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims priority to U.S. Provisional Application No.

60/209,876, filed June 6, 2000, and U.S. Application No. 09/705,373, filed November 2, 2000, both of which are incorporated herein by reference in their entirety for all purposes.

BACKGROUND OF THE INVENTION The present invention relates generally to information management. More particularly, the invention relates to systems and methods for populating a secured database with medical data, such as genetic data.

Conventional techniques for accessing medical information include expert systems for such medical information. These systems include manual based systems, systems that are internally networked only, systems that are narrowly focused and oftentimes not aggregated. Additionally, they often cannot perform multiple tasks when requested to do so. Further, there are also no common threads to bring information together, since the systems are often decoupled from each other. The framework is still trial and error and self taught and have many other limitations. There are also conventional techniques for conventional clinical trial recruitment strategies, which are not driven by patients. Here, a physician often reaches out to capture patients through word of mouth and referral. These may include soliciting focus groups, charitable groups, hospitals or other establishments, but do not usually include contacting the patient directly but via an intermediary. These methods are often limited both geographically and temporally.

Conversely, patients desiring to participate in studies, clinical trials or to gather information may use their physician, focus groups, charitable or disease specific groups, hospitals or other sources of information. Medical information may also be available through a worldwide area network, but it is a novel aspect of this invention to allow the patient to volunteer or participate in studies or clinical trials. Accordingly, conventional techniques for gathering and using medical information are limited.

One solution to the disparate medical information dilemma, is disclosed in U.S. Patent No. 6,082,776. As taught therein, medical information is encoded in an alphanumeric code that is then imprinted on a wallet-sized card or "sticker" wherein relevant medical history is contained using high order data compression techniques. In order to translate this visible code back into the original medical information, the code is dictated by human voice over a telephone to a remote PC with special software installed. A one page personal medical history may be generated in two to three seconds and then faxed back to the caller. The invention is designed for emergency use and many other types of medical encounters.

In addition, U.S. Patent No. 5,974,389 discloses a patient medical record system that includes a number of caregiver computers, and a patient record database with patient data coupled to the caregiver computers. Thus, the system provides access to the patient data from the caregiver computers responsive to predetermined access rules. The predetermined set of rules includes a rule that access to a portion of the patient data by a caregiver is terminated before access to the same portion by a second caregiver is allowed. From the above, it is seen that methods for providing medical information

(e.g., family history, lifestyle, clinical and medical history, therapies, phenotype) that is capable of being subtyped with additional medical information, e.g., diagnostic procedures, therapeutic, symptoms, and the like is needed.

SUMMARY OF THE INVENTION

The present invention generally relates to identifying populations of individuals for medical characterization through a worldwide area network of computers. According to the present invention, a technique for identifying populations of individuals for medical characterization through a worldwide area network of computers is provided. In an exemplary embodiment, the present invention provides systems and methods for identifying populations of individuals, which can each provide information (e.g., family history, lifestyle, clinical and medical history, therapies, phenotype) that is capable of being subtyped with additional information, e.g., diagnostic procedures, therapeutic, symptoms, and the like. In a specific embodiment, a method for populating a secured database with genetic data for use in clinical studies is provided. The method includes providing a server coupled with a worldwide network of computers, and providing a website configured to create trust of the website by users. The method also includes providing medical questiomiaires on the website to obtain information from a user, and analyzing the information obtained from the user to determine whether to invite the user to submit a biological tissue sample. The method further includes inviting a user to submit a biological tissue sample, and transmitting from the server to the user instructions for submitting a biological tissue sample. The method additionally includes receiving a biological tissue sample from the user, and analyzing the biological tissue sample to obtain genetic information. The method still further includes populating the secured database with the genetic information.

In another embodiment of the invention, the method further includes obtaining an informed consent of the user prior to receiving the biological tissue sample. The method according to the invention provides several advantages. It provides a highly efficient way to obtain phenotypic and genotypic data, because much of the recruitment is done with the website. A website may provide worldwide coverage at a relatively small cost as compared to past recruitment techniques. It also provides a highly efficient way to compile a rich database that may be used for many different uses, including numerous clinical studies.

In an exemplary embodiment, the database is populated using genetic data from mammalian fetuses such as human fetuses, and can be used in prenatal genetic testing. Using information derived form the database, neuro-degenerative disorders such as Huntington's disease, mental illnesses, certain types of cancer such as breast or prostate cancer can be identified. Birth defects such as spina bifida or an inherited disorder such as dwarfism or cystic fibrosis can be identified in unborn mammals.

In yet another embodiment, the present invention provides a computer program product for populating a secured database with genetic data in a networked environment. The networked environment includes at least one client connected to at least one server by a network. The computer program product includes code for providing medical questionnaires on a website to obtain information from a user. The computer program product also includes code for analyzing the information obtained from the user to determine whether to invite the user to submit a biological tissue sample. Further, the computer program product includes code for inviting a user to submit the biological tissue sample. The computer program product of the present invention also includes code for transmitting from the server to the user instructions for submitting the biological tissue sample. The computer program product further includes code for populating the secured database with genetic information obtained from the biological tissue samples received from the user, and a computer readable storage medium for holding the codes.

These and other embodiments of the present invention, as well as its advantages and features are described in more detail in conjunction with the following figures and the detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a simplified overall system diagram according to an embodiment of the present invention; Fig. 2 is a simplified overall system diagram according to an embodiment of the present invention;

Fig. 3 illustrates a representative networked environment for embodying the present invention;

Fig. 4 is an illustration of a representative computer system in an embodiment according to the present invention;

Fig. 5 is an illustration of basic subsystems of the system of Fig. 4; and Figs. 6A and 6B illustrate a simplified flow diagram of a method according to an embodiment of the invention;

Fig. 7 illustrates a simplified flow diagram of a method according to an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS

In understanding the present inventions and describes, it may assist the reader the understand the following terms, which are defined below.

Phenotype: This term is defined by any observable or measurable parameter, either at a macroscopic or system level (e.g., hair color, hair pattern, organ function, age, ethic origin, weight, level of fat) or microscopic or even cellular or molecular level, e.g., organ function, cellular organization, mRNA, intermediary metabolites). Phenotype can also be defined as a behavior pattern, sleep pattern, anger, hunger, athletic ability. There can be many other types of phenotypes, depending upon the application, which should not unduly limit the scope of the claims herein. Genotype: This term is defined as used herein broadly refers to the genetic composition of an organism, including, for example, whether a diploid organism is heterozygous or homozygous for one or more alleles of interest.

Patient Aggregate Server: The patient aggregate server is independent from health care providers and the like in some embodiments.

The above definitions are merely intended to assist the reader. Depending upon the application there may be other variations, modifications, and alternatives. One of ordinary skill in would recognize these.

According to the present invention, a technique for identifying populations of individuals for medical characterization through a world wide area network of computers is provided. In an exemplary embodiment, the present invention provides a method for identifying populations of individuals, which can each provide information (e.g., family history, lifestyle, clinical and medical history, therapies, phenotype) that is capable of being subtyped with additional information, e.g., diagnostic procedures, therapeutic, symptoms, and the like.

Fig. 1 is a simplified hub-spoke diagram 100 according to an embodiment of the present invention. This system is merely an example that should not unduly limit the scope of the claims herein. One of ordinary skill in the art would recognize any other variations, alternatives, and modifications. As illustrated in Fig 1, the present invention provides an infrastructure wherein genetic information and genetic services are provided to patients, physicians, and pharmaceutical firms, and others in a networked environment (e.g. Internet). In various aspects, the present invention provides a hub 102, wherein the spokes comprise patients 110, physicians 120, health care service providers 125, hospitals 130, HMO's 140, mental health clinics 145, and pharmaceutical firms 150. The hub 102 is a central repository, which can receive and deliver genetic infonnation about disease-specific genetic information. In certain instances, the patients, physicians, hospitals, pharmaceutical firms, etc., share genetic histories of individuals and populations. The hub contains large assemblies of data, which comprise genotype data, phenotype data, family and medical histories and other pertinent health related information. The compiled genetic infonnation is then used in diagnostic discoveries, targeted patient marketing, clinical trial recruitment and gene (SNP) identification and discovery.

The hub 102 provides a trusted relationship as the recipient and deliverer of large amounts of medical and genetic information. The trusted relationships in many instances are developed as a continuum, wherein as the relationship is developed over time and interaction, so is the trust. As the hub provides content, programming and genetic information services, the spokes become willing partners and trusted relationships are developed. Fig. 2 is a simplified system diagram 200 according to one embodiment of the present invention. This system is merely an example that should not unduly limit the scope of the claims herein. One of ordinary skill in the art would recognize any other variations, alternatives, and modifications.

In general, the present invention is preferably practiced within a client/server-programming environment. As is known by those skilled in this art, client/server is a model for a relationship between two computer programs in which one program, the client, makes a service request from another program, the server, which fulfills the request. Although the client/server model can be used by programs within a single computer, it is more commonly used in a network where computing functions and data can more efficiently be distributed among many client and server programs at different network locations.

Many business applications being written today use the client/server model as does the Internet's main program, TCP/IP. Typically, multiple client programs share the services of a common server program. Both client programs and server programs are often part of a larger program or application. Relative to the Internet, a Web browser is a client program that requests services (the sending of Web pages or files) from a Web server (e.g. Hypertext Transport Protocol or HTTP server) in another computer somewhere on the Internet. Similarly, a computer with TCP/IP installed allows client requests for files from File Transfer Protocol (FTP) servers in other computers on the Internet.

Moreover, client/server environments may include public networks, such as the Internet, and private networks often referred to as "Intranets" and "Extranets." The term "Internet" shall incorporate the terms "Intranet" and "Extranet" and any references to accessing the Internet shall be understood to mean accessing an Intranet and/or and Extranet, as well. The term "computer network" shall incorporate publicly accessible computer networks and private computer networks.

Although the above has been described in terms of a hub and spoke configuration, there can be other configurations. For example, the configuration can also include a distributed database form, where information is shared between databases at different geographical locations. Additionally, the configuration can include application server provider models, and others format 'models well known to those of skill in the art. Of course, the type of configuration used depends upon the application, among other features. Fig. 2 illustrates a client/server computing system in which the present invention may be embodied. In the illustrated system, a remote user's computer 201 has a client application resident thereon and a host computer 207 has a server application resident thereon. The user's computer 201 includes a communications link for communicating with the host computer 207. The communications link may be established via a modem connected to traditional phone lines, an ISDN link, a Tl link, a T3 link, via cable television, via an ethernet network, and the like. The modem may also be a wireless modem configured to communicate with the modem of the host computer 207 via wireless communications systems. The communications link also may be made by a direct connection of the user's computer 201 to the host computer 207 or indirectly via a computer network, such as the Internet 210, in communication with the host computer 207. Preferably, the communication link between the user computer 201 and the host computer 207 is via the Internet 210.

Preferably, a user's computer 201 has an Intel Pentium^® processor (or equivalent) with at least thirty-two megabytes (32 MB) of RAM, and at least five megabytes (5 MB) of persistent computer storage for caching. However, it is to be understood that various processors may be utilized to carry out the present invention without being limited to those enumerated herein. Although a color display is preferable, a black and white display or standard broadcast or cable television monitor may be used. Exemplary user computers having a client application resident thereon may include, but are not limited to, an Apple^®, Sun Microsystems^®, IBM^®, or IBM^®-compatible personal computer. A user's computer 201, if an IBM^®, or IBM^®-compatible personal computer, preferably utilizes either a Windows^®, Unix^®, Linux^® or OS/2^® operating system.

A host computer 207 may have a configuration similar to that of a user's computer 201 and may include a central processing unit, a display, a pointing device, a keyboard, access to persistent data storage, and a communications link for connecting to the user's computer 201 via a modem or otherwise.

It is understood that a user's computer having a client application resident thereon or a host computer having a server application resident thereon or other apparatus configured to execute program code embodied within computer usable media, may operate as means for performing the various functions and carries out the methods of the various operations of the present invention.

The host computer comprises various databases 215, 216. The databases may be relational databases, distributed databases, or object-oriented databases or mixed object oriented databases. Exemplary database products with which the present invention may be implemented include, but are not limited to, IBM's DB2, Microsoft's Access and FoxPro, and database products from Oracle, Sybase, and Computer Associates.

In certain instances, a biological tissue sample is obtained from a user. Here, the user can obtain packaging material, which houses the material. The material is sent via courier, mail, or the like to a laboratory. Alternatively, the user can go to a clinic, hospital, or laboratory, which takes the biological material from the user. The biological sample is thereafter analyzed and the genetic information obtained from the analysis is used to populate the genotype database 215. For example, blood, hair, urine, etc. from an individual is taken and their nucleic acid (e.g. DNA, RNA, etc.) is isolated and sequenced. The user's family and medical histories are compiled, and personal characteristics obtained voluntarily via the web site or through other health care providers 220 and are stored in database 216. The databases may be secured databases in order to protect the sensitive information obtained from the biological tissue samples.

In certain aspects, the healthcare aggregators are physicians, health care service providers, hospitals, HMO's, mental health clinics, pharmaceutical firms, or purveyors of healthcare information. In other instances, the user visits other Internet portals 219, which in some instances advertise the hub site. Users of the healthcare aggregators are tunneled to the hub site 207. In certain instances, trust is maintained as the goodwill associated with the aggregators is passed to the hub site. Fig. 3 represents one environment in which a method according to the present invention can be used. This diagram is merely an illustration and should not limit the scope of the claims herein. One of ordinary skill in the art will recognize other variations, modifications, and alternatives. Environment 300 includes a wide area network 309 such as, for example, the Internet. A plurality of individual clients 303, 305, 311 is connected to network 309. Also connected to the wide area network 309 is an information server 321, with terminal 313 and database 323. Wide area network 309 allows each of computers 303, 305, 311 and 321 to communicate with other computers and each other. Each of consumer computers 303, 305, 311 can be owned and operated by a different individual. Consumer computers can be configured with many different hardware components and can be made in many dimensions, styles and locations (e.g., laptop, palmtop, pentop, server, workstation and mainframe). For example, computer 303 can be at the home of a first individual, individual computer 305 can be at the home of a second individual, and consumer computer 311 can owned by a third individual, etc. Consumer computer e.g., 303 can include, as one example, conventional desktop personal computers or workstations having the ability to connect to network 309 and being capable of running customized software supporting the service provided by the present invention. Terminal 313 is connected to server 321. This connection can be by a network such as Ethernet, asynchronous transfer mode, IEEE standard 1553 bus, modem connection, universal serial bus, etc. The communication link need not be a wire but can be infrared, radio wave transmission, etc. Server 321 such as for the hub site, is coupled to the Internet 309. The Internet is shown symbolically as a cloud or a collection of server routers 309. The connection to server 304 to the Internet is typically by a relatively high bandwidth transmission medium such as a Tl or T3 line.

Internet server 321 and database 323 store information and disseminate it to individual computers e.g. 305 over wide area network 309. The method according to the present invention can be used for identifying and inviting users to submit a biological tissue sample for analysis in a networked environment 300. Server 321 connected to wide area network 309 stores webpages on an electronic database 323. The concepts of "client" and "server," as used in this application and the industry, are very loosely defined and, in fact, are not fixed with respect to machines or software processes executing on the machines. In this respect, a computer or process can be acting as a client at one point in time (because it is requesting information) and can be acting as a server at another point in time (because it is providing information). Some computers are consistently referred to as "servers" because they usually act as a repository for a large amount of information that is often requested. For example, a WEB site is often hosted by a server computer with a large storage capacity, high-speed processor and Internet link having the ability to handle many high-bandwidth communication lines.

With respect to the electronic database 323, it generally contains webpages, questionnaires, and forms. The database 323 can be composed of a number of different databases. These databases can be located in one central repository, or alternatively, they can be dispersed among various distinct physical locations. These databases can be categorized and structured in various ways based on the needs and criteria of the database designer. Methods used to create and organize databases are commonly known in the art, for example, relational database techniques can be used to logically connect these databases. Preferably, as shown in Fig. 3, the database of databases 323 can be physically located separate from the processor. These databases can reside on remote, distant servers on a local area network or the Internet. Under this arrangement, whenever any data are needed, the processor needs to access the necessary database(s) via a communication channel to retrieve the requisite data for analysis. For example, the processor can access and retrieve data from a remote database via a computer network such as a LAN or the Internet.

The embodiment shown in Fig. 3 also includes a database 325 for storing phenotypic and genotypic information. The database 325 can be composed of a number of different databases. These databases can be located in one central repository, or alternatively, they can be dispersed among various distinct physical locations. These databases can be categorized and structured in various ways based on the needs and criteria of the database designer. Methods used to create and organize databases are commonly known in the art, for example, relational database techniques can be used to logically connect these databases.

In one embodiment, the database 325 is a secured database to protect the highly sensitive phenotypic and genotypic information of individuals. In another embodiment, the database 325 is not accessible from the wide area network 309. Fig. 4 illustrates a representative system according to a particular embodiment of the present invention. This diagram is merely an illustration and should not limit the scope of the claims herein. One of ordinary skill in the art will recognize other variations, modifications, and alternatives. Embodiments according to the present invention can be implemented in a single application program such as a browser, or can be implemented as multiple programs in a distributed computing environment, such as a workstation, personal computer or a remote terminal in a client server relationship. Fig. 4 shows computer system 410 including display device 460, display screen 430, cabinet 440, keyboard 450, scanner 460 and mouse 470. Mouse 470 and keyboard 450 are representative "user input devices." Other examples of user input devices are a touch screen, light pen, track ball, data glove and so forth. Fig. 4 is representative of but one type of system for embodying the present invention. It will be readily apparent to one of ordinary skill in the art that many system types and configurations are suitable for use in conjunction with the present invention.

Mouse 470 can have one or more buttons such as buttons 480. Cabinet 440 houses familiar computer components such as disk drives, a processor, storage device, etc. Storage devices include, but are not limited to, disk drives, magnetic tape, solid state memory, bubble memory, etc. Cabinet 440 can include additional hardware such as input/output (I/O) interface cards for connecting computer system 610 to external devices external storage, other computers or additional peripherals.

Fig. 5 is an illustration of basic subsystems in computer system 510 of Fig. 4. This diagram is merely an illustration and should not limit the scope of the claims herein. One of ordinary skill in the art will recognize other variations, modifications, and alternatives. In certain embodiments, the subsystems are interconnected via a system bus 520. Additional subsystems such as a printer, keyboard, fixed disk and others are shown. Peripherals and input/output (I/O) devices can be connected to the computer system by any number of means known in the art, such as serial port 530. For example, serial port 530 can be used to connect the computer system to a modem, which in turn connects to a wide area network such as the Internet, a mouse input device, or a scanner. The interconnection via system bus 520 allows central processor 500 to communicate with each subsystem and to control the execution of instructions from system memory 510 or the fixed disk, as well as the exchange of information between subsystems. Other arrangements of subsystems and interconnections are readily achievable by those of ordinary skill in the art. System Memory 510, and the fixed disk are examples of tangible media for storage of computer programs, other types of tangible media include floppy disks, removable hard disks, optical storage media such as CD-ROMS and bar codes, and semiconductor memories such as flash memory, read-only-memories (ROM), and battery backed memory. The computer program product of the present invention allows individual to track the progress of studies, and disease development online.

A method according to the present invention related to studying a genetic basis for diabetes is briefly described below. 1. Provide client device;

2. Connect client device to a web site of a patient aggregating server through a world wide network via a portal or a search engine or browsing or other techniques, where the server includes sub-sites defined by a phenotypic characteristic, e.g., disease, baldness, weight condition, atrophy; 3. Select via an input device one or more of the phenotypic characteristics, that comprises a plurality of web pages;

4. Prompt a web page directed to the phenotype characteristic comprising a branding (e.g., expert in the field, easy to use, up to date information, intelligible and useable) that has good will associated with the phenotype characteristic;

5. Prompt a privacy statement to create goodwill and trust between the user and the web site;

6. Prompt a business concept to create further goodwill and trust between the user and the web site; 7. Optionally, prompt a registration form with a plurality of fields for input of user information;

8. Enter user information (e.g., e-mail, and name) into the registration form;

9. Transmit the user information from the client device to the server; 10. Maintain a plurality of the user information in an aggregate form without disclosing the name of any one of the users to a third party;

11. Once trust has been created between the user and the web site, prompt a request for a biological sample (e.g., blood) from the user;

12. Fill in the request form by the user; 13. Transfer the request form from the client to the server device;

14. Acknowledge receipt of request form to client device; and

15. Schedule appointment or sampling for the user and transmit the schedule to the user;

16. Collect the sample from the user and store the sample with the user information directed to phenotype information;

17. Provide an incentive to the user at any one of the above steps; and

18. Repeat the above steps for other users.

The above steps are merely an example that should not limit the scope of the claims herein. One of ordinary skill in the art would recognize many other variations, alternatives, and modifications.

A method according to the present invention related to studying a phenotypic and genotype basis for a health trait and forming a database of such basis is briefly described below.

1. Provide client device; 2. Connect client device to a web site of a patient aggregating server through a world wide network via a portal or a search engine or browsing or other techniques, where the server includes sub-sites defined by a phenotypic characteristic, e.g., disease, baldness, weight condition, atrophy; 3. Select via an input device one of the phenotypic characteristics, which comprises a plurality of web pages;

4. Prompt a web page directed to the phenotype characteristic comprising a branding (e.g., expert in the field, easy to use, up to date information, intelligible and useable) that has good will associated with the phenotype characteristic; 5. Prompt a privacy statement to create good will and trust between the user and the web site;

6. Prompt a business concept (e.g., bonus points, infonnation, incentive award, and certificate) to create further goodwill and trust between the user and the web site; 7. Optionally, prompt a registration form with a plurality of fields for input of user information;

8. Enter user information (e.g., e-mail, and name) into the registration form;

11. Once trust has been created between the user and the web site, prompt a request for human biological sample (e.g., blood) from the user;

14. Acknowledge receipt of request form to client device;

16. Collect the sample from the user and store the sample information with the user information directed to phenotype information;

17. Provide an incentive to the user at any one of the above steps;

18. Repeat the above steps for other users;

19. Aggregate the user information directed to the phenotype information and the biological (e.g., blood sample) information in the database; 20. Query the database for a given phenotype (or a given biological trait) to correlate the biological information;

21. Identifying the biological information or portion of the biological information or any relationship to the biological information (or phenotype information) related to each other for the given phenotype (or given biological information); and

22. Repeating the above steps 19-21 for other phenotypes (or other biological information).

A method according to the present invention related to facilitating the obtaining of a human biological sample from a patient using the Internet is briefly described below.

I . Provide client device; 2. Connect client device to a web site hosted by a server through a world wide network using a URL of the web site or a bookmark or via a portal or a search engine or browsing or other techniques;

3. Prompt a webpage that provides general information describing a process for volunteering to participate in a genetic study that may include submitting a DNA sample and asks whether the user is interested in volunteering;

4. Select via an input device to proceed;

5. Prompt a registration form;

6. Enter user information (e.g., name, nickname, password, etc.) into the registration form to establish a login and password for permitting access to a secured area of the website;

7. Transmit the user information from the client device to the server;

8. Prompt a terms and conditions of the website form;

9. Select via an input device to formally agree with the tenns and conditions of the website; 10. Prompt a terms and conditions of the genetic study form;

I I . Select via an input device to formally agree with the terms and conditions of the genetic study;

12. Prompt a general medical questionnaire form; 13. Enter user information via an input device into the general medical questionnaire form;

14. Transmit the user information from the client device to the server;

15. Based upon an analysis of the transmitted user information entered into the general medical questionnaire form, optionally prompt a detailed medical questionnaire form;

16. Enter user information via an input device into the detailed medical questionnaire form;

17. Transmit the user information from the client device to the server; 18. Analyze the user information associated with the general medical and detailed medical questionnaire forms;

19. Based upon analysis of the questionnaire fonn, formerly invite user, via e.g. email, mail, telephone call, etc., to submit a biological sample (e.g. blood) and direct user to the secured area of the website; 20. Connect client device to a login webpage for logging into the secured area of the web site;

21. User logs into secured area of website using login name and password established in step 6;

22. Prompt a webpage that provides a links to a consent form for preview by user;

23. Prompt a webpage that explains options (e.g. at home, at office, at a donation site) for submission of biological tissue sample (e.g. blood);

24. Prompt a webpage that lists a phone number that user may call to set up appointment for submission of biological tissue sample; 25. Obtain from user an executed informed consent fonn that was executed in the presence of a person;

26. After receiving tissue sample, prompt an email to user thanking user and including specific instructions on how user can rescind the informed consent agreement and request that the tissue sample be destroyed and their genetic data be deleted.

27. Analyze sample, and input genetic data into a database. The above steps are merely an example that should not limit the scope of the claims herein. One of ordinary skill in the art would recognize many other variations, alternatives, and modifications.

Figs. 6A and 6B is a simplified flow chart illustrating an embodiment of a method according to the present invention. The method facilitates identifying and recruiting volunteers to submit biological samples and phenotypic data to a database for further medical studies.

In a step 601, a user is asked to login to a secured area of a website. The login process may occur in any number of well-known ways. For example, the user may be asked to enter a previously established login name and a previously established password. In order for a user to obtain a login name and password, the user may optionally be required to formally agree to temis and conditions of the website.

In a step 603, the user is prompted to fill out a general medical questionnaire form on the website. A completed general medical questionnaire form is transmitted to the website server in a manner well known in the art.

In a step 605, the information transmitted in the completed general medical questionnaire form is analyzed to determine whether to not invite the user to participate or whether to obtain further information from the user before making a decision to invite. Based on the analysis, if it is determined that further infonnation from the user is desired, the method proceeds to step 607. Otherwise, the user is not invited to participate.

In step 607, the user is prompted to fill out a detailed medical questionnaire form on the website. A completed detailed medical questionnaire form is transmitted to the website server in a manner well known in the art.

In a step 609, the information transmitted in the completed detailed medical questionnaire form is analyzed. In one embodiment, the information is analyzed to detennine whether or not to invite the user to participate. In another embodiment, the information is further analyzed to determine whether additional information is needed before making a decision. If so, the method reverts back to step 607 where the user is prompted to fill out another detailed medical questionnaire form on the website. In yet another embodiment, the information may be analyzed in comparison to information obtained via the general medical questionnaire and/or other detailed medical questionnaires to determine the accuracy of the submitted information. Based upon the determined accuracy, the user may not be invited to participate. If it is determined to invite the user to participate, the method proceeds to step 611. ' In step 611, the user is formally invited to participate. The invitation may take the form of a phone call, mail, email, or the like. In one embodiment, the invitation may direct the user to proceed to a secured area of the website, using the user's login name and password. In another embodiment, the user may be asked to establish another login name and or password to obtain access to the secured area of the website.

In a step 613, an infomied consent of the user is obtained before the user may participate. In one embodiment, the secured area of the website may provide instructions to the user for executing an informed consent form. Additionally, the website may provide an infomied consent form for preview by the user. In one embodiment, the user may be required to execute the informed consent fonn in the presence of a person. The person may be a representative or agent of the database operator. In another embodiment, the person may be a third party. The person may attempt to verify the identity of the user. Additionally, the person may attempt to verify that the user is adequately informed. In another embodiment, the user may execute the informed consent form electronically via, for example, a digital signature, encryption, or the like. In this embodiment, a person as described above may communicate with the user via telephone, email, Internet, and the like.

In a step 615, a biological tissue sample is obtained from the user. The biological sample may be a blood sample, saliva sample, hair sample, and the like. The user may be instructed to go to a specific location. Also, the user may be given the option of arranging for submitting the sample at the user's home or office. The website may include a list of sample submission options, locations, phone numbers, instructions, and the like.

In a step 617, the biological tissue sample is analyzed using any one of numerous methods known in the art. In a step 619, the information obtained from the analysis is used to populate a database. The database may be a secured database in order to protect the sensitive information obtained from the biological tissue samples. In one embodiment, the database is not accessible via the Internet. The database may be, for example, the database 325 of Fig. 3. The databases thus populated can be used for a variety of purposes, including genetic testing. For instance, in certain embodiments, the present invention provides a method for providing prenatal diagnosis of a fetus. Fig. 7 illustrates a representative flow diagram 700 of a method according to a particular embodiment of the present invention. This flow diagram is merely an illustration and should not limit the scope of the claims herein. One of ordinary skill in the art will recognize other variations, modifications, and alternatives

Prenatal diagnosis is the assessment of the medical condition of a mammalian fetus, such as a human fetus. In certain aspects, the method of diagnosing a fetus provides taking a family a history 710. For example, if a mother says the fetus is not kicking as much as her previous child, this could be an indication of certain genetic disorders in the fetus. In addition, physical examinations can be performed 720. For example, physicians can hear the fetal heartbeat with a stethoscope. Moreover, physicians can also tell, with their hands, whether the fetus is growing nonnally over time. The method includes perfonning imaging tests (e.g., MRI, CAT scan or ultrasound). These tests produce pictures of the fetus. Ultrasound examinations are commonly used to detect twins and a variety of medical conditions. High-dose X rays can be harmful to the fetus, so X-ray tests are rarely performed. The method includes performing bodily fluid (e.g., blood and tissue) tests. Once the sample is obtained, chemical and genetic comparison tests can be performed.

Advantageously, prenatal diagnosis can detect threats to the health of the mother or fetus early. Physicians can therefore be prepared if the threats materialize. In some instances, surgeons can operate on the fetus before birth to correct problems. Occasionally, prenatal testing will disclose a very severe problem with the fetus. This could be a visible physical problem or an invisible genetic problem. In such cases, parents face the difficult decision of whether to continue the pregnancy or not.

In certain instances, genetic counselors work with physicians to offer information on the medical consequences of genetic disorders, the probability of developing a disorder or of passing it to offspring, and ways in which the disorder can be prevented or treated. Counselors provide literature for patient education, make patients aware of support groups and community resources for particular disorders, and offer ways to cope with the consequences of genetic disorders. They also can explain inheritance patterns, recurrence risk, prenatal diagnosis, and medical consequences of various disorders. In this way, the genetic counseling provides information and support to: patients affected with genetic disorders; parents at risk for having a child with an inherited disorder; and family members at risk for genetic disease. Moreover, the genetic counselors are trained and certified in genetic counseling or nursing degrees with specialties in genetics. They take family histories and prepare pedigree charts to help explain inheritance of the disorder. They are also trained to deal with the sometimes- devastating emotional consequences of the findings of genetic testing, using techniques of crisis intervention.

Some of the situations in which a genetic counselor might help include the presence of, for example, family history of late-onset disorders with genetic components. This includes neuro-degenerative disorders such as Huntington's disease, mental illness such as schizophrenia or manic-depressive psychosis, and certain types of cancer such as breast or prostate cancer. Other situations include, but are not limited to, birth of a child with a birth defect. Examples are spina bifida or an inherited disorder such as dwarfism or cystic fibrosis; family history of a relative with a birth defect or genetic disorder stillborn infant; recurrent miscarriage or infertility; exposure to a chemical or other agent known to cause birth defects.

A wide variety of physical examinations 720 (e.g., imaging tests) can be used. In a preferred embodiment, ultrasound is used. Ultrasound is a painless procedure that forms an image of the fetus by using sound waves. Echoes from the sound waves can be converted into a video image called a sonogram, which is displayed on a TN monitor. While the image may be difficult for a layperson to interpret, the parents can see major physical features such as head, arms, and legs, watch movements of the fetus, and even see behaviors such as thumb sucking. The sex of the fetus frequently can be determined as well. In operation, a hand-held device called a transducer is rubbed gently over the expectant mother's abdomen, which has been coated with a lubricating jelly. The transducer produces harmless sound waves, which bounce off the fetus and produce an image. If the woman is in the first trimester of pregnancy, a vaginal rather than an abdominal approach may be used. For vaginal ultrasound, a special tampon-shaped transducer is inserted in the vagina. For abdominal ultrasound, the woman must have a full bladder in order to get good images.

Ultrasound provides important medical information. Scans may be performed between the 12th and 16th weeks of pregnancy to determine fetal age and to detect twins. Scans performed between 16 and 18 weeks may be used to diagnose a number of birth defects. This includes hydrocephalus, limb or organ deformities, and some types of dwarfism, some heart defects, and neural tube defects such as spina bifida, in which the neural tube does not close properly.

A prenatal ultrasound examination may also be used to: diagnose an out- of-place pregnancy (ectopic pregnancy) where the fetus is growing not in the uterus, but in the fallopian tubes or abdomen; determine the rate of growth of the fetus; check for a fetal heartbeat if a possible miscaniage is suspected; and evaluate the position of the fetus prior to amniocentesis or CNS procedures (see below). Ultrasound is a painless procedure that is safe for both mother and fetus. Another examination method is amniocentesis. Amniocentesis is a diagnostic procedure that withdraws amniotic fluid from the uterus — specifically from the amniotic sac around the fetus. Because the cells in the amniotic fluid originate from the fetus, they can be used to obtain genetic infonnation about the fetus.

The method includes withdrawing a physical sample 730 for the fetus or from around the fetus (including the placenta, etc.), to generate a genetic profile 740 of the fetus. Preferably, amniocentesis is used to withdraw amnionic fluid. Amniocentesis can be performed in the second trimester of pregnancy, between 16 and 18 weeks. After anesthetizing the mother's abdomen with local anesthetic, the doctor uses a long needle to withdraw a sample of the amniotic fluid sunounding the baby. Ultrasound scanning during the procedure guides the needle away from the fetus. Once the cells are retrieved, they are allowed to grow and multiply. Some time later, technicians perform the following steps:

(i) They extract chromosomes from the cells.

(ii) They stain the chromosomes with special chemical dyes. (iii) They photograph the chromosomes with a microscope and camera,

(iv) They areange the chromosome pictures in a standard way, called a karyotype.

(v) They look for abnormalities in the karyotype, such as extra chromosomes, missing chromosomes, and broken chromosomes. Amniocentesis has been most useful in detecting visible problems with the chromosomes, as mentioned above. Down's syndrome is an example. People with Down's syndrome have three copies of chromosome 21 instead of two. Chromosomes can also disclose the sex of the fetus. A female fetus has two X-chromosomes. A male fetus has one X and one Y chromosome. Using amniotic fluid, it is also possible to run tests that, in an adult or child, would normally be performed on a blood sample. These include, but are not limited to, detecting the blood type. The "Rh" blood type is commonly checked, since an Rh-positive fetus in an Rh-negative mother can cause problems if untreated. Measuring the levels of certain chemicals. This can detect metabolic problems ~ problems involving how the fetus processes certain chemicals ~ such as Tay-Sachs disease. It can also detect high levels of "alpha-fetoprotein," which suggests there is a problem with the developing brain or spine. Performing gene testing. Gene testing for the fetus is no different, in principle, from gene testing in adults and children. On average, one miscarriage occurs for every 200-400 procedures performed in the second trimester of pregnancy (see, www.modimes.org/Default.htm). The risk for miscarriage is higher if amniocentesis is perfonned earlier in the pregnancy. Because of this risk, amniocentesis should be used cautiously. Another disadvantage of amniocentesis is that it is performed in the second trimester of pregnancy and because it takes some time to obtain a chromosome analysis, the pregnancy is fairly advanced before the results are known. If the parents choose to terminate the pregnancy, there can be greater risk to the mother associated with later termination.

Another physical sample technique is chorionic villus sampling (CNS). The chorionic villus is part of the placenta. It originates with the fetus and has the same genetic information as the fetus. Thus, chorionic villus sampling (CNS) is another way to look at fetal chromosomes. This procedure is generally offered when parents want to know about possible genetic abnormalities as soon as possible. CNS can be performed in the 10th to 14th week of pregnancy, which is earlier than amniocentesis can be performed. Also, the analysis takes less time, so results are available more rapidly than with amniocentesis.

During CNS, doctors remove a tiny sample of the chorionic tissue, which is a part of the placenta. Using ultrasound as a guide, the doctor inserts a small tube into the vagina and through the cervix to collect a tiny sample at the edge of the placenta using gentle suction. No anesthetic is required. Sometimes the sample is taken through the abdomen in a fashion similar to amniocentesis. A picture of the chromosomes

(karyotype) can be prepared from this tissue sample. Results are generally available in ten days. CNS is used for the same reasons as amniocentesis, with the exception of neural tube defects, which this test is unable to detect.

The risk of miscarriage from CNS testing is slightly higher than with amniocentesis. If the expectant mother is experiencing spotting or bleeding, CNS should not be performed because risk of miscarriage is even higher. CNS has major shortcomings. Although it is performed earlier and gives couples more time to make a decision to terminate a pregnancy, CNS is not as accurate as amniocentesis. CNS collects placental cells, which may have an abnormal chromosome profile even when the fetus is normal. While diagnoses made with amniocentesis are 95% accurate, CNS returns an accurate diagnosis only 50% of the time according to some studies. Use of this technique might, therefore, result in selective abortion of normal fetuses (see, Stranc LC et al., Lancet, 1997; 349:711-714). Another physical test 730 that can be performed is the triple screen test.

The triple screen is a blood test that examines the level of three substances in the mother's bloodstream: (i) alpha-fetoprotein, a protein produced by the liver of the fetus; (ii) estriol, a pregnancy hormone; and (iii) human chorionic gonadotropin (HCG), another pregnancy hormone. In this test, blood is drawn from the expectant mother between 16 and 18 weeks of pregnancy. A laboratory then measures the levels of the three substances. Elevated levels of alpha-fetoprotein can indicate the presence of a neural tube defect such as spina bifida or anencephaly. (Anencephaly is failure of the brain to develop.) Low levels of alpha-fetoprotein and estriol, combined with elevated levels of HCG, can indicate Down syndrome. However, abnormal levels in the triple screen test are not by themselves diagnostic. They merely indicate a risk and that further tests, such as ultrasound, amniocentesis, or CNS testing are indicated. Triple screen testing of maternal blood has aided in prenatal diagnosis of 95 percent of cases of anencephaly, 80 percent of cases of serious spina bifida, and 60 percent of cases of Down syndrome (see, http://www.modimes.org/Default.htm). Risks of the triple screen test are the same minimal ones associated with having blood drawn for any other purpose.

While the invention has been described with reference to certain illustrated embodiments this description is not intended to be construed in a limiting sense. For example, the computer platfonn used to implement the above embodiments include 586 class based computers, Power PC based computers, Digital ALPHA based computers, SunMicrosystems SPARC computers, etc.; computer operating systems may include WINDOWS NT, DOS, MacOs, UNIX, VMS, etc.; programming languages may include C, C++, Pascal, an object-oriented language, etc.

Various modifications of the illustrated embodiments as well as other embodiments of the invention will become apparent to those persons skilled in the art upon reference to this description. As will be appreciated by one of skill in the art, the present invention may be embodied as a method, data processing system, or computer program product. Accordingly, the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment or an embodiment combining software and hardware aspects. Further, aspects, of the present invention may take the form of a computer program product on a computer-usable storage medium having computer-usable program code means embodied in the medium. Any suitable computer readable medium may be utilized including hard disks, CD-ROMs, optical storage devices, or magnetic storage devices.

All publications, patents and patent applications mentioned in this specification are herein incorporated by reference into the specification in their entirety for all purposes. Although the invention has been described with reference to prefened embodiments and examples thereof, the scope of the present invention is not limited only to those described embodiments. As will be apparent to persons skilled in the art, modifications and adaptations to the above-described invention can be made without departing from the spirit and scope of the invention, which is defined and circumscribed by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A method for populating a secured database with genetic data for . use in clinical studies, the method comprising: providing a server coupled with a worldwide network of computers; providing a website configured to create trust of the website by users; providing medical questionnaires on the website to obtain information from a user; analyzing the information obtained from the user to determine whether to invite the user to submit a biological tissue sample; inviting a user to submit a biological tissue sample transmitting from the server to the user instructions for submitting a biological tissue sample; receiving a biological tissue sample from the user; analyzing the biological tissue sample to obtain genetic information; and populating the secured database with the genetic information.

2. The method of claim 1, further comprising obtaining an informed consent of the user prior to receiving the biological tissue sample.

3. The method of claim 2, wherein the informed consent is an executed informed consent form executed in the presence of a person.

4. The method of claim 2, wherein the informed consent is an executed informed consent form executed using a digital signature.

5. The method of claim 1, wherein the website includes a privacy policy statement.

6. The method of claim 1, further comprising providing the user with a secure password for accessing a secured area of the website.

7. The method of claim 1, wherein biological tissue sample is e.g. blood, saliva, hair, urine, skin, biopsy, etc.

8. A system for populating a secured database with genetic data, the system comprising: a server coupled with a worldwide network of computers, the server configured to host a website that creates trust of the website by users; a secured area of the website configured to transmit instructions for submitting biological tissue samples; a module for providing medical questionnaires on the website to obtain information from a user; a module for analyzing the information obtained from the user to determine whether to invite the user to submit a biological tissue sample; a module for inviting a user to submit a biological tissue sample a module for transmitting from the server to the user instructions for submitting a biological tissue sample; and a module for populating the secured database with genetic information obtained from biological tissue samples received from the user.

9. A method for providing prenatal diagnosis of a fetus, said method comprising: taking a family history of the parents of said fetus to ascertain certain genetic disorders; performing a physical examination of said fetus to ascertain certain genetic disorders; withdrawing a physical sample from said fetus or around said fetus to generate a genetic profile of said fetus; and comparing said genetic profile of said fetus against a database of genetic profiles, thereby providing prenatal diagnose of said fetus.

10. The method of claim 9, wherein said database populated via a website configured to create trust.

11. A computer program product for populating a secured database with genetic data in a networked environment, said networked environment comprising at least one client connected to at least one server by a network, said computer program product comprising: code for providing medical questionnaires on a website to obtain information from a user; code for analyzing the information obtained from the user to determine whether to invite the user to submit a biological tissue sample; code for inviting a user to submit the biological tissue sample; code for transmitting from the server to the user instructions for submitting the biological tissue sample; code for populating the secured database with genetic information obtained from the biological tissue samples received from the user; and a computer readable storage medium for holding the codes.

12. The computer program product of claim 11, wherein said code for analyzing the information is executed at said server.