Diagnostic Kits

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Introduction to Genetic and Genomic Diagnostics

The field of Biotechnology is a critical US industry, by some estimates approaching 2% of the US GPD and growing 15% per year. Genetic and Genomic research represent a core focus of R&D in the biotechnology industry. Over the last 40 years, improvements in sequencing technology have led to massive increases in test precision and overall throughput capacity. These advances have bolstered the breadth of genetic and genomic research, and have allowed these fields to transcend from mere laboratory concepts to a number of practical, real world applications.

Today, these research efforts have contributed clinical diagnostic methods of testing that are capable of providing information specific to the genetic characteristics of an individual. The logical core of diagnostics is the link between a health state, such as a disease or drug response, and particular genetic sequence (often a mutation therein). Once this link is clinically established, a test can readily be developed based on existing techniques. Thus, the actual methods that are developed are not often based on new measurement or sampling techniques, but rather, newly discovered links between genotype and phenotype.

Through these tests a clinician can perceive a wealth of information, including an individual's disposition to develop complex diseases over time, such as cancer, heart disease, asthma, and diabetes, and allow the clinician to advise practical changes in lifestyle to minimize health future health risks or maximize preventative medical care. In cases where disease may already be present, some tests are useful for determining more efficient methods of treatment that are specific to that individual. The diagnostic tests range from single tests which evaluate a single gene and its affects to others, which are more comprehensive, and can evaluate samples on the genomic level, which are capable of analyzing multiple genetic factors.

These tests represent valuable assets to the companies who develop them and bring them to market in the form of consumer product offerings. Currently, diagnostic tests are being marketed to the public in a three different ways: Laboratory Developed Test Services, In Vitro Diagnostic Kits, and Tests Sold Directly to Consumers. It should be no surprise that these companies seek robust legal protection for their investments through intellectual property ("IP") law. For instance, many companies obtain patents for their inventions that grant them a legal mechanism to exclude others from utilizing their research and development efforts. However, these protections occasionally affect research and development efforts of others in these fields negatively.

Emerging research in genetic and genomic diagnostics presents unique challenges for IP considerations. Changes in laboratory research due to actual or anticipated patent or license enforcement could signal the failure of protections secured through intellectual property to spur the innovations such protections are intended to promote. These issues are at the center of our research efforts under the Industrial Cooperation Project at the Harvard University's Berkman Center for Internet & Society. This research is part of a broader project being led by Professor Yochai Benkler. Through the research, we seek to understand the approaches to innovation with genetic diagnostic kits, and look specifically to the barriers to use and innovation.

Defining Genetics and Genomics

Occasionally, the terms "Genetics" and "Genomics" are used interchangeably within the context of genetic testing. More specifically, both terms are sometimes used to refer to the testing of specific genes or the indexing of multiple tests of single genes. Although we note there is a difference in these terms, we use these terms synonymously, except where specifically noted otherwise.

The difference between these terms is scientifically important because they refer to distinct concepts. These terms are often confused because the distinctions between "genetic" and "genomic" diagnostics are rarely delineated well, if at all. Consequently, discussions of their market, innovation cycles and the impact of intellectual property in the emergence of open or closed arrangements of cooperation is less than precise.

The Distinctions Between Genetics and Genomics

In simple terms, "Genetics" can be defined as the scientific study of single genes and their effects. Genes are units of heredity that carry the instructions for making proteins, which direct the activities of cells and functions of the body. Genetics is also term that refers to the study of genes and their role in inheritance - the way certain traits or conditions are passed down from one generation to another. Genes influence traits such as hair and eye color as well as health and disease development. Genetics determines much, but not all, of a person's appearance and health status. Environmental factors also play a part. Many disorders of the human body, such as disease and illness, are linked to abnormal gene function. For example, single gene disorders include cystic fibrosis and PKU (phenylketonuria). For more examples, see National Human Genome Research Institute and The Centers for Disease Control and Prevention.

Thus, "genetic testing" or "diagnostics" is testing of singular genes, by assaying a relatively small sample containing DNA, to determine genotype and identify genetic abnormalities known to be link to disease. Additionally, these tests can determine the prognosis of disease, potential responses to drug treatment, and other factors related to the state of health of the sample provider.

On the other hand, "genomics" is a relatively new term that describes the study of all of a person's genes including interactions of those genes with each other and the person's environment. genomics involves the scientific study of complex diseases such as heart disease, asthma, diabetes and cancer because they are caused more by a combination of genetic and environmental factors. genomics is offering new possibilities for therapies and treatment of some diseases, as well as new diagnostic methods. The major tools and methods related to genomics studies are bioinformatics, genetic analysis, measurement of gene expression, and determination of gene function. More at Genome.gov and at and at CDC.gov genomics and Health Resources and CDC.gov Genomics Translation Resources

However, the phrases "genetic testing" "genomic testing" tend to be used differently than their respective scientific meanings. The majority of genetic tests that are available today are based on second generation sequencing platforms. Today, this type of diagnostic refers to the testing of fractions of the complete human genome of a person. These tests evaluate multiple genes and are significantly larger than what is typically analyzed in a typical singular gene sequencing test. Although whole genome sequencing is possible, these tests are quite expensive and the term "genomic testing" is used to refer to the tests of portions, or fractions, of the entire genome. Perhaps, a more apt term to define this type of diagnostic, is "multiplex genetic tests," because they represent genetic diagnostics that are highly parallelized and have a relatively high-throughput, but are not based on a complete genome sequence.

These multiplex or multiple gene tests are capable of many more measurements than genetic tests. Often these tests completely sequence several genes to the entire genome, or of hundreds of thousands of SNPs from a genomic sample and tend to use microarrays (sometimes called SNP chips or gene chips) or second generation (still called "next-generation" sequencing circa 2010), high-throughput DNA sequencing. Microarrays are widely used in direct-to-consumer genomic diagnostics designed to provide risk profiles for many genetic diseases at once. These tests are highly useful for more complex diseases that caused by multiple genetic abnormalities, rather than single abnormal genes. In this sense, genomic tests "provide comprehensive genetic risk profiles for many diseases or targeted genetic risk profiles for specific conditions." Examples of disease caused by multiple genetic disorders include asthma, heart disease, autism, cancer, and hypertension.

So, how can you determine whether a company is offering a genetic test, a genetic test that samples multiple genes, or a genomic test? It's often very difficult to determine on the basis of pure marketing materials. However, many company and laboratory website offer information which explain some of the scientific underpinnings on the services they offer. More often than not, a genetic testing service will not offer a low-cost genomic test--i.e., one that sequences that entire genome. Instead, these laboratories offer singular or multiple gene tests and combine the results into a single report. There are some laboratories who offer full genome sequencing, but these tests are priced into the tens of thousands, to hundreds of thousands dollar range in the U.S.

See our sample list of laboratories who offer genetic and genomic testing services below.

Genetic Test Applications

Genetic tests are conducted through a variety of different testing procedures. Primarily, diagnostics utilize biochemical, cytogenetic, molecular, or a combination of these methods, to analyze DNA, RNA, chromosomes, proteins, and metabolites. Genetic tests may be conducted as Clinical Tests, Research Tests, Investigative, or Recreational Tests. Note that these terms are distinct from the technical methods used in a diagnostic. Rather than describing the procedure, they describe the utility, clinical validity, or purpose of a test.

Test Type Purpose of Test
Clinical Tests Clinical level tests are used to examine sample specimens of individual patients for diagnosis, prevention, or treatment of genetic related disorders. The test results are reported from the laboratory back to the patient in writing. Laboratories who conduct these types of tests must be approved by the Clinical Laboratory Improvement Amendments (or "CLIA") program.
Research Tests Research tests are conducted in laboratories and research centers to study and understand genetic conditions or to develop clinical level tests. These tests are not subject to CLIA approval and are conducted for internalized research purposes to develop advances in testing.
Investigative and Recreational Tests Investigative and Recreational tests are considered valuable tests, but are those that have not gained either scientific validity or acceptance in the medical community. In short, these tests often are perceived to lack the accuracy of clinical level tests. Moreover, laboratories conducting these tests are not subject to CLIA approval.


Clinical Diagnostics Testing Purposes

The largest category of diagnostic tests are used for clinical applications - i.e., in the course of treatment or diagnosis of diseases, and in the course of preventative medical care. In most circumstances, these tests are ordered by medical professionals. The following table illustrates the range testing purposes.

Test Objective Description
Diagnostic These tests are used to confirm when a person has signs or symptoms of a genetic disease. The tests are tailored for diagnosing a particular disease. This includes diseases such as Down Syndrome and Duchenne Muscular Dystrophy. These types of diseases are linked to specific genetic disorders. If signs are present, such as the physical attributes associated with Down Syndrome, a genetic test can be used to determine if the patient has the extra copy of Chromosome 21.
Predictive A predictive genetic test indicates a person's propensity to develop a disease before any symptoms are present. These types of tests are used for certain cancers, such as breast, colon, and ovarian cancer. The results of the tests can predict, with a margin of error, a person's percentage likelihood of developing these diseases over their lifetimes. Usually, externalized factors, such as age and lifestyle, are taken into consideration with the results to bolster test accuracy.
Presymptomatic Presymptomatic tests are similar to predictive tests. These tests are used to determine risk for genetic conditions that are already known to be present in their family, but show no symptoms. Diseases such as Huntington's and Grave's disease are among commonly screened in presymptomatic testing. The test results allow doctors to give medical advice, and take preventative actions, to decrease the likelihood of occurrence or increase the chances of successful treatment.
Preconception/Carrier Preconception or Carrier Tests can determine if individuals "carry" a alterations in their genes that are associated with an "autosomal recessive order." In short, people have a higher likelihood of developing certain diseases if they inherit two copies of altered chromosomes from their parents. If two people each have a copy of one chromosome, their children have a much higher likelihood of developing diseases such as Cystic Fibrosis and Tay-Sachs Disease.
Prenatal Prenatal tests are used to test fetuses during the course of pregnancy. These tests are especially useful for scenarios where a fetus has a higher likelihood of developing diseases. For instance, if both parents are carriers of genes related to autosomal recessive disorders, or where family history indicates a likelihood of development of Huntington's and Grave's disease.
Newborn Similarly, newborn babies may also be screened after birth, or at an early age, when circumstances indicate a likelihood of development. For instance, one test analyzes blood samples for abnormal or missing genes or the presence of Phenylkentonuria (PKU), a type of metabolic disease that can cause severe mental retardation without early treatment.
Pharmacogenic Pharmacogenic screening is a type of genetic test that may indicate a person's response to certain types of drug treatment. This type of test can enable practitioners to select the best methods of treatment after a disease as already been diagnosed.


How Genetic Tests are Developed by Manufacturers and Laboratories

The process of developing and marketing a genetic test is riddled with technicalities of oversight by the FDA and a handful of other U.S. regulatory agencies. In summary, there are two pathways that developers typically take in the course of bringing a genetic test to market. First, some tests are developed as full testing kits by manufacturers of medical devices. These testing kits are classified by the FDA as "in-vitro diagnostic" (IVD) devices and subsequently sold to laboratories who conduct the actual testing services. Second, some tests are developed solely by laboratories as "laboratory developed tests" (LDTs) for use in-house, solely within the laboratory, and are not sold to any outside entities.

At the heart of almost every genetic test, whether considered an IVD or an LDT, are the "active ingredients" needed to conduct the test. These ingredients usually constitute analyte-specific reagents (ASRs), which are specially prepared polyclonal or monoclonal antibodies - biochemical substances that are used in a genetic test to identify or quantify certain chemical substances or ligands in biological specimens. Once an person with the proper skill has the correct ASRs, he or she only needs the necessary equipment and instructions on testing procedures and result interpretation, a genetic test can easily be conducted. Since the ASRs are so critical to the test itself, they often represent a significant amount of research and development effort on behalf of the company or laboratory who formulates the ASRs.

Interestingly, the federal regulations which govern IVDs and LDTs have left what many commentator believe to be regulatory loopholes that make development of a LDT genetic test the more attractive pathway than a IVD. Perhaps for this reason the majority of genetic tests available are LDTs. For more information on the regulatory aspects of IVDs and LDTs see our U.S. Regulatory Review Page

IVDs

As mentioned, "testing kits" are IVDs under the FDA regulations. The final product of a testing kit typically contains a series of instructions that detail how to conduct the test and the necessary ASRs to conduct the test. These tests are regulated as "medical devices" under FDA regulations and are subject to stringent regulation. The FDA oversees and require certain approvals and certification before such a device can be sold on the market. For many IVDs, these regulations include the approval prior to sale on the market, oversight of all aspects of the production process and ultimate sale of the IVD, and oversight of the actual testing procedures within laboratories to ensure the IVD is safe and effective for its intended purposes.

LDTs

LDTs can be developed in two ways. First, the majority of LDT tests utilize ASRs which are developed in-house, solely for use within the laboratory. The test designs and procedures are proprietary to the laboratory and are not sold for use to any outside entities. In short, the laboratory is markets the test to and obtains the necessary specimens directly from consumers. Once received, the specimen is processed in the test and results are reported directly back to the consumer in writing or on the internet through a secure website interface. As previously mentioned, this type of LDT is not subject to the same level of regulatory oversight as is an IVD.

A second, but somewhat less common method of developing an LDT, is accomplished when a laboratory develops the test design and procedures, but does not develop the necessary ASRs for use in the test. Instead, the laboratory obtains the ASRs by purchasing them from an outside entity and incorporates the ASRs into their test. In this circumstance, the test is marketed and conducted in the same manner as the other type of LDT. Unlike the completely proprietary LDTs which are not subject to stringent regulation, the process of purchasing ASRs is subject to some regulation, but still not as much as is the IVDs. Importantly, the sellers of the ASRs, rather than the LDT laboratories, tend to be the entities who must satisfy federal regulations for the sale of ASRs. For this reason, this type of LDT is still an attractive option when a laboratory cannot develop and entirely proprietary LDT.

How Genetic Tests are Marketed and Accessed by Consumers and Patients

Patients and Clinically Ordered Tests

Traditionally, the pathway for a patient or consumer to access genetic testings has been through a medical professional, such as a physician, who clinically orders a test in the course of medical care to for the purposes of diagnosis or disease prevention. These tests allow medical professionals to obtain information about a patient's predisposition to certain diseases, or to diagnose an individuals current illness, future illness, or predict the responsiveness of certain drugs in treatment.

After determining that a genetic test is appropriate, a family doctor, or other health care professional, will typically use a genetic "test kit," which has been supplied by a manufacturer or laboratory. The test kit contains instructions on how to obtain specimen and submit it to the laboratory (sometimes a separate entity than the manufacturer) for testing . Specimens can range from a buccal (saliva) swab to blood or bodily tissue. Once collected, the specimen is sent to the laboratory for testing. The results are reported back to the doctor directly along with instructions to aid in the interpretations of results. Of course, following the results, the doctor can then advise the patient with recommendations for treatment or preventative care.

These testing kits are generally considered "medical devices" by the FDA and are subject to stringent level of oversight that governs the device prior to its sale on the market, to the process of manufacturing the kits, and the laboratory testing procedures. For more information on the regulatory aspects of genetic testing, see out U.S. Regulatory Overview page.

Tests Marketed Directly to Consumers

Although medical professionals continue to order and use genetic testing in the course of clinical care, the decrease in cost and increase in availability of testing services has made it easier for patients and consumers to access genetic testing without the need of a visit to a physician's office. Essentially, consumers have directly access to genetic testing services directly through laboratories marketed through online websites or by purchasing over-the-counter kits from retail stores. No prescription or order by a medical professional is necessary. These tests are commonly referred to as direct-to-consumer (DTC) tests, a reference to how such tests are marketed to consumers. Within the DTC paradigm, patients and consumers typically mail a specimen, like a buccal swab or smear, in a container to a laboratory or company which then processes the test and provides test results in writing or over a secure internet interface. These results remain private to the consumer and are not included in any medical records.

DTC genetic tests purport to offer many similar capabilities - in terms providing information on health risks and disease disposition - as do the clinically ordered tests by a physician. Often these tests provide the consumer with either percentage of likelihood of developing a disease within one's lifetime. However, one significant difference between the physician-ordered tests and those sold directly to a consumer is that test results are often not interpreted by a medical professional. Instead, the company or laboratory who provides the testing services are communicate the test results combined with their own analytic interpretations directly to the consumer. Many commentators criticize DTC tests because they lack the personalized approach to test result interpretation by a professional, especially in instances where results indicate a percentage calculation which indicates potential health risks or status. More specifically, in many cases genetic testing services do not account for externalized environmental factors which are known to affect the probability of a person's health status.

Additionally, although the links between many genetic tests and occurrence of diseases are widely accepted in the scientific and medical communities, many genetic tests are not stringently regulated or approved by the FDA for use in the diagnosis or prevention of disease. This means that most DTC tests are not approved by the FDA prior to commercialization on the market and there is little oversight that governs the practices of companies and laboratories conducting such tests. In some circumstances, the methods of testing may vary widely. Some commentators, including a U.S. committee on genetics from the Department of Health and Human Services, are concerned that the differences between how test is prepared or conducted may ultimately affect the accuracy and proficiency of test results. Moreover, these discrepancies are often not well communicated to the consumers.

Since the awareness - and in particular, the almost prolific discussion in popular media - of genetic tests continues to increase, the future may hold more stringent regulations of genetic product marketing by the FDA and the FTC. For more information on the regulatory aspects of genetic testing, see out U.S. Regulatory Overview page.

Manufacturers and Laboratories who Develop or Offer Genetic Testing Services

Below is a list of companies known to market genetic testing. Where applicable and to the extent known, the list notes whether the testing services are being marketed directly to consumers as either a "direct-access" test or where test manufacturers and developers are selling testing "kits" as IVDs or LDT genetic testing services. Additionally, this list provides some distinction to testing services that provide full genomic sequencing or singular or multivariate gene testing.

Please note that there many companies and manufacturers involved in the development of genetic testing - this should not be considered a comprehensive list of market participants.

Genome Sequencing Manufacturers and Service Providers

Recreational and Clinical Genetic Testing Manufacturers and Service Providers

  • cpmc.coriell.org: Free Affymetrix GeneChip SNP sequencing, but only for "potentially medically actionable" conditions. Currently this list includes 10 conditions, and will grow as the Informed Cohort Oversight Board approves more conditions.
  • 23 and Me
  • DeCODEme.com: $195 - $985 for up to 48 genetic conditions using a 100,000 SNP chip. In Bankruptcy proceedings.
  • Counsyl.com: offers a (I presume) a chip-based screen for 100 genetic disease markers, including some for cystic fibrosis. Trying to sell both direct to consumers and clinically and aiming for insurance coverage. DTC costs $349. Not sure how they ensure the results are clinically useful.
  • Navigenics.com: offers chip-based testing for 28 different conditions along with personal genetic counseling for $999. Not sure how they ensure the results are clinically useful. Want to be clinically used.
  • PathwayGenomics.com: offers carrier testing for 61 genetic diseases, metabolism genes for 9 different drugs, as well as ancestry analysis for $199-$399. Not sure how they ensure the results are clinically useful.
  • DNADirect.com - not sure what their product is.
  • GenomicHealth.com / OncotypeDX.com : 21-gene expression assay that predicts recurrence of certain kinds of breast cancer. Considered a multivariate assay and regulated by the FDA; has more clinical data than most other genetic diagnostics demonstrating it's clinical validity and utility. Covered my insurance more often than other tests.

Laboratories

"The major national reference labs including Quest, LabCorp, Specialty/Ameripath, Mayo and others account for at least 60% of the market for esoteric test services. The remaining 40% is shared by a group of some 3000 small, local market laboratories. The major reference labs have built a comprehensive menu of specialized test services and continue to expand their offerings via collaborations with leading medical research centers. They offer a huge presence in the market and manage distribution networks that touch just about every medical specialty. Thus many CLIA-registered company sponsored test services avail themselves of the marketing resources offered by the national reference labs."

Quest and Labcorp are the two most dominant national reference labs. Financial information can be gotten from the SEC by using the Standard Industrial Classification 8071: Services - medical laboratories, which includes Quest, Lab-Corp, Bio-Reference, Athena, and ~120 others.

  • LabCorp wikipedia. LH stock symbol. (SEC CIK# 0000920148)
    • 2008 10-K - Annual Report
      • Net Sales of Genomic & Esoteric tests: $1,478.3 Million (+5.9% from 2007)
      • Volume of Genomic & Esoteric tests: 23.7 Million
      • Patents, licences, and technology "2008 gross carrying amount": 94.7 million

Legal Aspects of Diagnostics

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General Analysis of the field based on our ICP Main Questions

  1. Overview of Economics of Intellectual Property in Kits
  2. Give an overall picture of the Kits' sector
  3. Outputs and Products of the field: data, narratives and tools produced by the Kits' sector
  4. Legal tools available for and in use by the actors of Kits' sector: IP in Kits
  5. competitive advantages in Kits
  6. IP Profile of Biggest for-profit companies in Kits
  7. IP Profile of non-profit companies in Kits
  8. IP Profile of Universities working in Kits
  9. IP Profile of Associations in Kits
  10. Commons based cases in Kits
  11. Peer-Production Business models in Kits
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