Providing the individual with greater autonomy is a worthwhile goal although it is relevant to all aspects of clinical medicine, not only genetics. To say that genetics is different because genes somehow represent a more personal part of the individual is misleading as geneticists have tried to avoid this view with its implications for genetic determinism and stigmatization. There is little doubt that genetics, particularly in relationship to DNA and genetics, is complex, but whether it is different is arguable.
Making a decision on what tests are clinically useful is not easy with genetic DNA tests. Even more of an issue would be how to interpret the results, some of which will require considerable expertise which is unlikely to be possible without access to expert opinion including genetic counseling.
DTC DNA testing is a commercial venture, and so members of the community may be disadvantaged by not having access to these tests because of costs, availability of the Internet, or understanding what is for sale.
Evidence that results provided would lead to useful clinical interventions or decision-making is uncertain.
Protection for the individual, particularly in relation to privacy, may be compromised with DTC DNA testing conducted in overseas laboratories.
The consequences of DTC DNA testing on the individual (and family members) remain unknown including the potential for false-positive and false-negative results. The effects on the healthcare system should be considered.
DTC advertising can be misleading if the product sold appeared to have direct relevance to health and well-being, yet the accompanying disclaimer focused on the product as information which should not be used for medical decision-making.
DTC companies introduced innovative advertising strategies. For example, they made effective use of social media to facilitate connections with “genetically” similar friends. One company hosted a celebrity “spit” party to highlight this new type of testing. In 2008, Time magazine announced that the DTC DNA genetic test was the invention of the year [2]. Public interest in knowing about genetic discoveries and the potential for estimating health risk was considered significant, for example, ~75 % in one survey said they would be prepared to pay for this type of testing [2]. Apart from the media hype touting new genetic discoveries, there were optimistic estimates of the potential size of the DTC DNA testing market with one in 2007 predicting it would generate >$730 million annually with a 20 % growth rate. Subsequent predictions were more realistic although commercially viable such as the market in 2010 was worth ~$10–$20 million annually [2].
Medical Research
The DTC industry took advantage of the public’s interest in medical research to link DTC testing services with opportunities to allow the same DNA sample to be added to a DNA research bank. Justification was given as a way to obtain the large cohorts required for genetic research studies. Nevertheless, even with consent, there remained concerns such as (1) How did oversight or community expectations for medical research compare between different jurisdictions as samples to DTC laboratories came from multiple sources including offshore ones? This was particularly important for privacy. (2) What happened if the DTC DNA testing laboratory was sold or went into receivership? This became reality when the Icelandic company deCODE got into financial difficulties in 2009 and filed for bankruptcy. Apart from providing a DTC DNA testing service, deCODE had a very valuable commercial asset in its DNA biobank of 140,000 specimens linked to medical records [4]. At the time, there was concern that the DNA and medical information resource might be sold to pay creditors. Eventually, deCODE was sold, its DTC service discontinued, and the DNA biobank preserved for ongoing research.
Sales Product
DTC DNA testing services provided a range of services for (1) medical (health-related) disorders, (2) recreational purposes, (3) identification of human traits, and (4) forensic or legal testing. The medical testing services have been the subject of much debate and are the topic of this chapter. The other products particularly those for recreational purposes including family tracing (genealogy) and DNA testing to select better diets (nutrigenetics) or skin products (dermatogenetics) are much less controversial as caveat emptor applies like other commercial transactions. Debate continues on the ethical and societal implications of DNA genetic testing for human traits such as the prediction of athletic performance particularly in children, or identifying fetal sex during pregnancy for family balancing [2].
A key question with DTC DNA genetic testing is what actually is being sold? When viewing the companies’ Internet sites, the “average” reader might assume that medical-type DNA genetic tests are being advertised and so provide a result that could be used in personalized healthcare. Based on the result, some interventions would be possible leading to better health and well-being. Alternatively, when reading the various product disclaimers on the same Internet sites, the product for sale is described as “information” provided for this purpose alone.
Legally, there is some leeway in terms of what can be claimed in advertising. For example, saying that “product X is the best available” may not be entirely true, but in contemporary marketing, it might be reasonable to expect the “average” person will take this with a degree of cynicism and buy or not buy the product with this in mind. At worse, the person will lose money. On the other hand, the same flexibility may be problematic with health issues where the consequences for error are more significant.
Oversight
Some regulatory bodies struggled when it came to dealing with the somewhat vague concept of “information” because their governing Acts referred to more tangible products such as medical devices, drugs, and so on. Nevertheless, the claim that only “information” was being sold was criticized on ethical grounds if information was not guaranteed to have scientific relevance and/or even of being correct, unless these facts were clearly known at the time of purchase or consent.
It is important to distinguish DTC DNA genetic testing provided locally, i.e., by laboratories within the same regulatory or legal jurisdiction as the customer. In these circumstances the customer has a better understanding of and access to the relevant consumer protection laws including those relating to privacy. Should something go wrong, the customer can seek legal redress. In contrast, DTC offered in different jurisdictions particularly offshore laboratories places the customer at a significant disadvantage when things go wrong. Some might say the customer has little if any legal protection unless he or she understands the legal environment that the DTC testing company operates in and/or can afford to take legal action in that jurisdiction. Most DTC DNA testing providers are located within the USA [5].
Measuring the Clinical Value of a DNA Genetic Test
For a medical DNA genetic test (and any type of clinical investigational test), a number of criteria should be assessed before the test becomes a component of clinical care. The evaluative process can be demanding and time consuming but necessary to provide the evidence for decision-making. The same rigor is not required for DNA tests discovered as part of research activities as these tests are subject to ongoing scrutiny such as peer review. With accumulation of sufficient data, their clinical value would become apparent, at which time they could be discarded or moved into the more regulated clinical service. Various parameters listed below are used to assess the clinical value of laboratory tests. For genetic tests, there is also consideration of the ethical, legal, and social implications (ELSI).
Clinical Utility
An acceptable medical test should have clinical utility, i.e., the test should provide information from which health-related decisions/interventions can be made, and health-related risks should not occur as a consequence of the testing [6, 7]. Measuring clinical utility in mainstream medical practice is not always easy.
Some DTC product disclosure brochures are ambiguous when it comes to clinical utility. For example, one company’s Terms and Conditions for genetic predisposition testing states, (i) All materials and products ……..are provided for informational and educational purposes only. (ii) I agree not to hold ……liable for any damages caused as a result of the use of the information or products contained herein, and (iii) The purpose of the molecular genetic test is to ascertain if I, my child or an individual for ………………..are carrying mutation(s) predisposing to or causing the specific diseases or conditions covered in the ordered test [8].
In the above disclaimer, the consumer has conflicting information. First, the product is described as genetic predisposition testing. To a geneticist, this terminology means the DNA genetic test will provide information in the form of a risk estimate that in the future, a particular disease or trait will develop (or it will not develop) based on changes detected in a gene. So the product for sale seems to be a DNA genetic test providing information for medical decision-making as is further implied in part (iii) of the company’s disclaimer.
However, the disclaimer also states that the DNA genetic test is for informational and educational purposes only, which implies the product should not be used for medical decision-making. This ambiguity could be resolved with “truth in advertising” although, like the laboratory test, it would be difficult to regulate when it was provided through the Internet particularly offshore locations.
Clinical Validity
This measure describes the accuracy with which a test identifies a particular clinical condition [6]. For a number of DNA genetic tests for Mendelian-type genetic disorders such as Huntington’s disease (HD), the result is very accurate at detecting those with this disorder (sensitivity) or excluding those without the disorder (specificity). The DNA test itself measures the number of CAG repeats associated with the HTT gene. Those with ≥40 repeats have or will get this autosomal dominant disorder because the penetrance is 100 %. There is now sufficient clinical experience to allow reasonable interpretations to be made for different CAG repeat numbers (Fig. 21.1). Setting aside important considerations like the pre- and post-test genetic counseling requirements and ELSI associated with the HD predictive test, the clinical validity for this test is high even if offered DTC. In contrast, the clinical validity for more complex genetic disorders will be poor as illustrated below under Genetics to Genomics.
Fig. 21.1
Huntington’s disease (HD) DNA genetic testing. Although testing for a rare genetic disorder, the HD test is technically straightforward as it measures CAG repeat numbers located at the 5′ end of HHT. The start of the gene is depicted as an atg which is followed by a variable number of CAG repeats (capitalized). The interpretation of the result is unequivocal for normal or abnormal while results in the so-called intermediate range 27–39 require more care in understanding clinical significance for the person being tested and family members. This DNA test illustrates two different purposes for the same test. The diagnostic test is used to confirm that an individual presenting with a neurological disorder such as dementia or a movement disorder like chorea has HD. ELSI for this test is less of an issue as the patient has an existing medical problem and the test is simply confirming a clinical suspicion. In contrast, the same DNA test can be used to assess risk in family members and so becomes a predictive DNA test. ELSI is more significant because asymptomatic individuals are now tested. Whether the result comes back positive or negative has widespread implications for all, including risks to offspring and the possibility of not being able to access life (and in some jurisdictions health) insurance
Analytic Validity
This describes the technical ability of the DNA testing laboratory to carry out the test accurately. As shown in one study, analytic validity was not an issue in DTC DNA testing [9]. This can be attributed to the sophisticated analytic platforms now available for testing, many of which are automated. It is likely most laboratories that have undergone appropriate accreditation will be able to carry out DNA genetic testing satisfactorily. Therefore, the customer, when selecting a DTC DNA testing service, should know something of the accreditation standards, and this is more likely to be possible if the test is ordered from a local laboratory rather than an offshore one. The DTC company example quoted earlier is accredited to the international standard ISO 17025 [8]. However, in some jurisdictions such as Australia, this standard is not acceptable for medical DNA testing, and a higher one ISO 15189 is required [10].
Analytic validity is directed to the laboratory component of the test. However, there is an equally important second component to any DNA genetic test, and that is the result and what it means in the context of that individual’s health. As shown in the same publication which confirmed satisfactory performance for analytic validity in two USA-based DTC DNA testing companies, the interpretation of some laboratory results by these companies was poor since they reported different risks – both high and low for the same genetic disorder in the same customer [9]!
Ethical, Legal, and Social Implications (ELSI)
Another measure for the value of a DNA genetic test is its ELSI. Although more difficult to evaluate, ELSI should be considered particularly for DNA tests associated with significant risk [7]. For DTC DNA genetic testing, the following ELSI are relevant [2, 5, 7]: (1) Marketing, especially truth in advertising and consumer trust, (2) Psychosocial impact on the customer (and potentially family members), (3) Implications for the healthcare system, and (4) Privacy.
One complexity when considering the ELSI component of a DNA genetic test is the understanding that the same test can be used for different purposes. Therefore, potential advantages, disadvantages, and risks need to be considered for each test and the purpose of that test. Table 3.7 in reference [7] provides a classification of DNA genetic tests based on purpose. Further information may also be found in Chap. 10 in this book. Examples of three different tests follow to highlight considerations around ELSI.
First is the DNA diagnostic test, which would be relatively low risk from the ELSI perspective. In this scenario, the medical practitioner is dealing with a patient who has certain signs and/or symptoms consistent with an established clinical problem. The diagnostic DNA test forms part of the medical workup to identify the clinical problem. Even if the wrong DNA test is selected or the result of the DNA test is incorrect, it is likely the medical practitioner will, in the course of time, repeat the test or query its result because it will be inconsistent with the clinical phenotype. This type of follow-up is not likely in the DTC approach.
The second example is the predictive DNA test, which lies at the other end of the risk spectrum because it is looking into the future and assessing risk. The accuracy of this prediction may not be straightforward as it can be influenced by other genetic and/or environmental factors involved in pathogenesis. As well as accuracy, there is always the possibility of error with any laboratory test, and this should be discussed in the pretest counseling. Errors with predictive DNA tests (ordered by the medical practitioner or DTC) are particularly problematic because the patient is asymptomatic and so errors may not become apparent for years, by which time the patient and relatives will have made important life decisions based on incorrect DNA test information.
A third type of test offered DTC is based on research findings that may or may not have been confirmed. Internationally, there is strong interest in expediting the translation of medical research into clinical practice. While praiseworthy, this goal is problematic if research discoveries are used for clinical decision-making before sufficient evidence accumulates. The overlapping of research into clinical care is evident in the DTC industry which frequently promises the latest findings. One DTC DNA testing company advertised its medical testing products as (1) Established research reports (earlier described by the company as Clinical reports) and (2) preliminary research reports [7].
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