Skip Navigation U.S. Department of Health and Human Services www.hhs.gov
Agency for Healthcare Research Quality www.ahrq.gov
Archive print banner
Genetic Tests for Cancer

This information is for reference purposes only. It was current when produced and may now be outdated. Archive material is no longer maintained, and some links may not work. Persons with disabilities having difficulty accessing this information should contact us at: https://info.ahrq.gov. Let us know the nature of the problem, the Web address of what you want, and your contact information.

Please go to www.ahrq.gov for current information.

Part II: Genetic Tests in Development for Clinical Use

Aim

The aim of Part II of this project was to identify genetic tests currently in development for clinical cancer care. During this part of the project, one challenge was how to identify genetic tests "in development" that were pertinent to the purposes of this horizon scan. The methods section of this report details the systematic process that we developed and applied to the scientific and gray literature, in an attempt to identify cancer genetic tests with more immediate clinical and commercial potential.

The final product of this part of the project is a database of genetic tests currently in clinical development for cancer care. These tests were identified during our search of the scientific and gray literature as well as through other additional resources such as expert interviews and scientific conferences. The focus of this database was to find genetic tests that are currently under investigation for clinical utility. By the time most medical tests in development reach testing for clinical utility, the new technology in development usually is associated with commercial interests. As a result, the focus of our search for genetic tests in development centered around the LexisNexis® database, which provides access to authoritative legal, news, public record, and business information via a set of searchable databases that contain over 36,000 sources of print media including newspapers, magazines, and legal documents.

Return to Contents

Methods

Our approach to identify genetic cancer tests in this section can be divided into three separate processes:

  1. Searching the scientific literature.
  2. Searching the gray literature.
  3. Scientific meetings and expert interviews.

We began with a search of the scientific literature. However, as we learned from our efforts during Part I of this project, a systematic search of the scientific literature was not likely to be useful for the purposes of this horizon scan. As a result, the focus of our search for genetic tests in development centered on a systematic review of the gray literature and in particular LexisNexis, as the source of information most applicable to our horizon scan project.

Scientific literature search. A MEDLINE® search was conducted on July 12, 2005 to address the key question of identifying genetic tests in development for cancer. Briefly, we used search terms from 3 categories:

  1. Diagnostic test (i.e., sensitivity and specificity, mass screening, diagnosis, predictive value, ROC curve, likelihood ratio).
  2. Gene or genetic or genomic test.
  3. Top 10 cancers by mortality (lung, colon, breast, pancreas, prostate, leukemia, lymphoma, ovarian, esophagus, liver)*.

The complete search strategy used is detailed in Appendix A4. The results of this initial exploratory search of the scientific literature were presented and discussed at an interim conference call with AHRQ. Based on a sampling of the abstracts from the MEDLINE search, it was revealed that many of the studies identified as potentially of interest were preclinical exploratory reports of potential tumor biomarkers or genes/genomic arrays with possible associations with tumor diagnosis or activity. However, the chances that any of these early preclinical biomarker reports will eventually evolve into clinically validated and useful tests are slim.4 As a result, a significant majority of these reports would not be of interest or useful for the purposes of our particular horizon scan. Together with AHRQ, we decided to focus our energies toward searching gray literature sources.

Gray literature search. As discussed in Part I, in constructing our list of gray literature sources, we started with gray literature sources identified by the NLM's Health Technology Assessment Information Resources. 5 Furthermore, we supplemented this list of gray literature sources with additional databases through conversations with AHRQ (LexisNexis) and internal investigations (Google News, Early Research Detection Network, Cambridge HealthTech). By the end of this project, we identified 39 databases of interest; however, this list is not designed to be comprehensive. Below is a brief description of each gray literature source explored and the search strategies that we employed for each database.

For the purposes of this report, we have organized the gray literature sources that we examined into three categories:

Category I: (High utility for the horizon scan)

a. LexisNexis (www.lexisnexis.com)

LexisNexis provides access to authoritative legal, news, public record, and business information via a set of searchable databases that contain over 36,000 sources of print media including newspapers, magazines, and legal documents. Sources include public records, The New York Times, CNN, Bloomberg, Dun & Bradstreet, the Associated Press, Biotech Week, and NewsRx. This tool is the global legal and information division of Reed Elsevier.

We searched LexisNexis under the Medical News and Business News headings. Business News contained additional subheadings of interest: Industry News, Business and Finance, Mergers and Acquisitions, and Knight Ridder. For the purpose of our search, we began with the key terms "cancer" AND "test" covering a 1 year time period. We started with these terms to cast the widest net possible. However, if more than 1000 articles are returned for a search, LexisNexis does not provide individual title results. When this result occurred, we first altered the timeframe of our search and then added an additional search term in order to be more specific in our request. If >1000 articles were returned for 6 months of records, our search terms were changed to "cancer" AND "gene" AND "test." With either the two or three term combinations, we were able to generate a list of titles for a 1 year time period. (A time period of 1 year was chosen in the hope of capturing references to genetic tests that are more advanced in the clinical development process and perhaps more likely to be commercial available within a relatively short time. Therefore, by limiting our search to 1 year, we hoped to find genetic tests that might be relevant to CMS within the next 1-2 years, using the most efficient method possible.)

Two reviewers screened the list generated by the LexisNexis search for relevant titles. Complete articles were then retrieved for the titles identified as potentially applicable for our project. Articles were read by two reviewers and a group decision was made regarding whether to include or exclude the test from our database. When a test was identified for inclusion, pertinent test information was extracted from the report and entered into the database. If additional data on a particular technology was needed, we often were able to extract missing information from the developer's Web site.

b. Cambridge Healthtech Institute (CHI) (www.healthtech.com/)

The Cambridge Healthtech Institute has developed and released the "CHI ToolBar." The CHI Toolbar allows users to search eight different databases including the Biomedical NewsAnalyzer, which is a fully searchable, online database containing all press releases from many companies in the pharmaceutical, biotechnology, bioinformatics, diagnostics, medical device, equipment, drug delivery, contract research, and manufacturing industries. Additionally, this tool provides access to the Biomedical Industry Analyzer, a directory of over 4600 companies in these sectors.

We searched the CHI database with the key terms "cancer," "test," and "gene." These searches were limited to the field of oncology. We screened all of the titles that were obtained from these searches to identify reports of interest. Next, we retrieved and reviewed the full articles identified by our title screening and extracted pertinent information on potential genetic tests into our database.

Category II: (Low to moderate utility for the horizon scan)

c. Computer Retrieval of In formation on Scientific Projects (CRISP) (http://crisp.cit.nih.gov/)

CRISP provides a listing of federally funded research projects conducted at universities, hospitals, and other research institutions in the biomedical fields. This database is maintained by the Office of Extramural Research at the National Institutes of Health and includes projects funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), AHRQ, and Office of Assistant Secretary of Health (OASH).

We searched CRISP using the combination of key terms "cancer" AND "test" AND "gene." Two reviewers screened the titles for potential relevance and retrieved the complete reports for a sampling of projects. From the initial sampling of retrieved reports, it became evident that the CRISP database was limited to projects mainly investigating preclinical exploratory biomarkers or genomic arrays that might have an association with tumor diagnosis or activity. In this sense, CRISP provided information similar to a MEDLINE search or other traditional scientific literature databases. Therefore, after consulting with AHRQ, we decided that CRISP would be less useful to our specific task of identifying genetic tests in development.

d. Web of Knowledge (http://www.thomsonisi.com/)

ISI Web of Knowledge encompasses both multidisciplinary and specialized content as well as external collections, covering journals (including open access titles), books, proceedings, patents, chemical structures, evaluated Web content, grant funding, and preprints. All content in this database, including over 8,700 journals and 22 million patents, must meet editorial requirements to be included.

We searched Web of Knowledge using the key terms "cancer" AND "test" AND "gene" for a time period of 1 year. We screened a sampling of the titles that were obtained from these searches to identify reports of interest. We then retrieved the complete reports from a sampling of articles that represented promising leads for cancer genetic tests in development. From this sample of articles, it became evident that the Web of Knowledge is useful for identifying research of potential biomarkers that are mainly in the preclinical phase of development and far from establishing clinical utility or commercial development. In this respect, Web of Knowledge may be considered similar to MEDLINE searches and therefore, it was decided that this resource would not be useful for our purposes and further exploration of Web of Knowledge was discontinued.

e. Early Detection Research Network (EDRN) (http://www3.cancer.gov/prevention/cbrg/edrn/)

EDRN is a multi-disciplinary collaborative effort organized by the National Cancer Institute to identify and validate potential cancer biomarkers. EDRN focuses on speeding laboratory discoveries and their subsequent translation to clinical biomarkers. In addition, the goal of EDRN is to "provide timely, cost-effective clinical tests for early detection of cancer and identification of high-risk individuals."6 This network is comprised of the following main components:

  1. Biomarkers Developmental Laboratories, which develop and characterize new biomarkers or refine existing biomarkers.
  2. Biomarkers Reference Laboratories, which serve as a resource for clinical and laboratory validation.
  3. Clinical Epidemiology and Validation Centers, which conduct and support early phases of clinical and epidemiological research on the application of biomarkers.
  4. A Data Management and Coordinating Center, which provides statistical, logistics, information support, and develops theoretical statistical approaches to pattern analysis of multiple markers simultaneously.
  5. An Informatics Center led by investigators at the National Aeronautics and Space Administration (NASA)'s Jet Propulsion Laboratory serving as the lead for the informatics component.

Since the goals of EDRN appeared to be similar to the goal of our horizon scan, we decided to search the most recent EDRN report (March 2005) to identify potential genetic biomarkers and tests that could be added to our database. In order to stay consistent with our justifications for discontinuing extensive explorations of databases such as MEDLINE and Web of Knowledge, we only extracted biomarkers that had proceeded beyond the preclinical exploratory stage (phase 1 of development) and were at least being studied for clinical validity and utility (phase 2 and beyond). (Figure 1)

f. National Research Register (NRR) (www.nrr.nhs.uk/search.htm)

The National Research Register is a database of ongoing and recently completed research projects funded by, or of interest to, the United Kingdom's National Health Service. We searched The National Research Register using the combination of key terms "cancer,""test," and "gene," screening the titles to identify reports of interest. Next, we retrieved and reviewed the full articles that held potential for tests to be included in our database. However, the majority of potentially relevant articles, as hinted by their titles, referred to early preclinical, exploratory studies to identify potentially useful tests. As a result, we decided to discontinue further exploration of this resource.

g. Canadian Institute of Scientific and Technical Information (CISTI) (http://cisti-icist.nrc-cnrc.gc.ca/main_e.html)

CISTI is a source for information in all areas of science, technology, engineering and medicine. CISTI began over 75 years ago as the library of the National Research Council of Canada and became the National Science Library in 1957. It contains over 50,000 different serial titles, over 600,000 books, conference proceedings and technical reports, and 2 million technical reports from around the world.

We searched CISTI using the combination of key terms "cancer" AND "test" AND "gene." We screened all of the titles that were obtained from this search to identify reports of interest and pulled the full reports of articles that might fit our inclusion criteria above. Similar to NRR, the majority of titles screened in CISTI referred to phase 1 exploratory studies and were thus far from either commercial development or establishing clinical utility. We decided to discontinue further exploration of the CISTI database because of its limited utility to our horizon scan.

h. Google (www.news.google.com)

Google News gathers stories from more than 4,500 news sources in English worldwide and automatically arranges them to present the most relevant news first. Results are compiled solely by computer algorithms, without human intervention, and include articles that have only appeared within the past 30 days.

We searched Google News using the key terms "cancer" AND "test" AND "gene." We screened all of the titles that were obtained from this search for reports of interest, pulling the full articles of all titles of interest. Tests extracted from these articles of interest revealed significant overlap between Google and LexisNexis. In addition to this redundancy with LexisNexis, the Google search engine did not allow a search beyond 30 days. As a result of these limitations, we did not further explore Google for this horizon scan.

i. Clinical Laboratory Improvement Amendments (CLIA) (www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfClia/Search.cfm)

CLIA regulates all laboratory testing (except research) performed on humans in the U.S. In total, CLIA covers approximately 175,000 laboratory entities. The Division of Laboratory Services, within the Survey and Certification Group, under the Center for Medicaid and State Operations has the responsibility for implementing the CLIA Program. We searched CLIA using the simple search function with the key term "cancer." We screened all of the titles that were obtained from this search and pulled the full reports of all articles that might fit our inclusion criteria above. Review of these articles and tests of interest revealed that these sources focused mainly on genetic tests currently in use. Therefore, the CLIA database was probably more applicable and useful for Part I of this project.

j. The Office of In Vitro Diagnostics Device Evaluation and Safety (OIVD) (www.fda.gov/cdrh/oivd/consumer-otcdatabase.html)

OIVD is part of the U.S. Food and Drug Administration's Center for Devices and Radiological Health. OIVD regulates all aspects of in-home and laboratory diagnostic tests (in vitro diagnostic devices or IVDs), helps new IVDs reach the medical marketplace, prevents the sale of unsafe or ineffective IVDs, and categorizes the complexity of IVDs according to the Clinical Laboratory Improvement Amendments of 1988, thereby defining the type of regulatory oversight applied to the product.

We searched OIVD with the key term "cancer." We screened all of the titles that were obtained from this search and retrieved the full reports of all articles that had titles of interest. Review of these reports quickly revealed that all of the relevant reports in the OIVD database referred to tests already available for clinical use, thus making OIVD a resource more applicable for Part I of this project.

k. FDA Pre-market Approval (www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm)

The Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act (the act) established three regulatory classes for medical devices. The amendments define a Class III device as one that supports or sustains human life or is of substantial importance in preventing impairment of human health or presents a potential, unreasonable risk of illness or injury. All devices placed into Class III are subject to pre-market approval requirements. Pre-market approval by the FDA is the required process of scientific review to ensure the safety and effectiveness of Class III devices.

We searched the Pre-market Approval Database with the key terms "cancer," "test," and "gene." We screened all of the titles that were obtained from this search and retrieved the full reports of all articles of interest. Similar to OIVD, we found that the Pre-market Approval database identified tests already available for clinical use, thus making it a resource more applicable for Part I of this project.

l. ClinicalTrials.gov (www.clinicaltrials.gov)

ClinicalTrials.gov provides regularly updated information about federally and privately supported clinical research in human volunteers. ClinicalTrials.gov gives you information about a trial's purpose, who may participate, locations, and phone numbers for more details. We searched ClinicalTrials.gov using the combination of key terms "cancer" AND "test" AND "gene." We screened all of the titles that were obtained from this search strategy and retrieved the full reports of the titles of interest. Similar to NRR and CISTI, most reports in ClinicalTrials.gov refer to genetic tests in preclinical phase 1 exploratory studies and could be considered too premature for either commercial development or establishing clinical utility. Therefore, we limited further exploration of ClinicalTrials.gov database due to its limited utility to our particular horizon scan.

m. Online Computer Library Center (OCLC)'s FirstSearch (www.oclc.org/firstsearch/)

The OCLC FirstSearch database retrieves records from worldwide conferences, symposia, meetings, expositions, and congresses. This database covers a number of disciplines including the arts, humanities, social sciences, and physical and life sciences. Within the FirstSearch database, we searched PapersFirst from 2004 to 2005 using the key terms "cancer" AND "test" AND "gene." We screened all of the titles that were obtained from this search but were unable to proceed further because the database did not allow access or retrieval of abstracts or full text reports.

n. Health Technology Assessment Database (HTA) (www.york.ac.uk/inst/crd/htahp.htm)

The Health Technology Assessment (HTA) database contains information on healthcare technology assessments and is produced in collaboration with the International Network of Agencies for Health Technology Assessment (INAHTA) Secretariat, based in Sweden. The database contains records of ongoing projects being conducted by members of INAHTA, as well as publications reporting completed technology assessments carried out by INAHTA members and other health technology assessment organizations.

We searched this database using the key terms "cancer" AND "test" AND "gene." We also applied the same search terms to the Data Abstracts of Reviews of Effects and Health Assessment Technology Database. As indicated by their titles, these technology assessments review analytical and clinical utility data on genetic tests already in use. Therefore, the HTA database would be more relevant for Part I of this project.

o. NY Academy of Medicine (www.nyam.org/)

The Gray Literature Report is a quarterly publication of the New York Academy of Medicine Library, alerting readers to new gray literature publications in public health as they are acquired. This report was first published in 1999 and acquires materials from various organizations publishing gray literature and gives them special cataloging treatment.

We searched the Gray Literature section of the Academy using the terms "cancer," "test," and "gene." We screened all of the titles that were obtained from this search and retrieved the full reports of all articles of interest. A quick review of these titles and abstracts revealed that this database produced reports that were not specific to genetic tests in development. The few reports that did involve genetic testing usually contained clinical and analytical data for already established technologies.

p. GrayLIT Network (http://graylit.osti.gov/)

The GrayLIT Network is a portal for technical report information generated through federally funded research and development projects. It was developed by the Department of Energy's Office of Scientific and Technical Information, in collaboration with the Department of Defense/Defense Technical Information Center (DOD/DTIC), NASA, and the Environmental Protection Agency. The GrayLIT Network was released in early response to recommendations from a May 2000 workshop on the concept of a "Future Information Infrastructure for the Physical Sciences" held at the National Academy of Sciences.

We searched the GrayLIT Network with the combination of terms: "cancer," "test," and "gene." We screened all of the titles that were obtained from these searches and retrieved the full reports of a sampling of articles of interest. Abstracts from the GrayLit Network mainly referred to tests in a preclinical exploratory phase of development, similar to several databases mentioned earlier. As a result, we did not choose to explore this database in further detail for the purposes of this project.

q. Health Services Research Projects in Progress (HSRProj) (www.academyhealth.org/hsrproj/search.htm)

HSRProj contains descriptions of research in progress funded by federal and private grants and contracts for use by policy makers, managers, clinicians, and other decisionmakers. It provides access to information about health services research in progress before results are available in a published form.

We searched HSRProj with the terms "cancer," "test," and "gene." We screened all of the titles that were obtained from this search and pulled the full reports of a sampling of articles that might fit our inclusion criteria. The HSRProj database identifies research focused on health services research and not on test development. As a result, we limited our use of this resource for this horizon scan.

Category III: (Not useful for the horizon scan)

r. Other

We identified several additional gray literature tools available to explore. However, further investigation of these sources revealed that none of the resources would be useful for our horizon scan project. Table C lists these gray literature resources that we identified but did not use for any part of this project. Reasons for not using some of these resources include: no search engine, subscription services that we were unable to access, or services clearly oriented toward literature that was not applicable to our horizon scan on genetic testing in cancer.

Opinion leaders and scientific conferences. Interviews were conducted with different experts representing commercial laboratories, academic hospitals, and the FDA. Academic and government leaders were identified during our scientific and gray literature searches, including the EDRN network of principal investigators and consultants. Opinion leaders were affiliated with the University of Chicago, the FDA, Quest Diagnostics, and Roche Diagnostics. In addition, we attended two scientific meetings; (1) "Pharmacogenomics in Drug Development," a workshop jointly sponsored by the Drug Information Association, FDA, Pharmacogenetic Working Group, PhRMA, and the Biotechnology Industry Organization, and (2) the 2005 American Society of Clinical Oncology (ASCO) Annual Meeting.


*Top 10 cancers in estimated deaths based on data from American Cancer Society Surveillance Research, U.S. Mortality Public Use Data Tapes, 1969-2002, and National Center for Health Statistics, Centers for Disease Control and Prevention, 2004.


Return to Contents
Proceed to Next Section

The information on this page is archived and provided for reference purposes only.

 

AHRQ Advancing Excellence in Health Care