‭Week 8 Lecture 1‬

‭ creen Tests: Genetic Testing in the Nursery and the‬

S
‭Workplace‬
‭Using a case as a framework to discuss policy theories that underlie that policy formation‬
‭●‬ ‭Don't memorize cases for the exam‬

‭Midterm‬
‭●‬ ‭Tuesday October 29‬
‭●‬ ‭60 questions‬
‭●‬ ‭8:30 - 10:20 am‬

‭Screen Tests…Genetic Testing in the Nursery and the Workplace‬

‭●‬ ‭“‭G ‬ enetic testing‬‭is a powerful tool that can help identify individuals at high risk for disease‬
‭and/or vulnerability to environmental chemical hazards. However, there are numerous individual‬
‭and societal implications regarding when these tests should be required, who should have access‬
‭to test results, and what can be done with the information.‬
‭●‬ ‭Two scenarios are presented:‬
‭○‬ ‭genetic screening in the context of reproductive decisions, and‬
‭○‬ ‭genetic testing for insurance and employment purposes.‬
‭●‬ ‭This case addresses several policy issues, including:‬
‭○‬ ‭Screening;‬
‭○‬ ‭Insurance‬
‭○‬ ‭Ethical issues relating to individual vs. societal rights, including issues of:‬
‭■‬ ‭Autonomy;‬
‭■‬ ‭Privacy;‬
‭■‬ ‭Risk of discrimination on the basis of genetic test results..”‬
‭●‬ ‭(Deber and Mah, 2014)‬
‭●‬ ‭This case talks a lot about screening, recap of screening (re: tuberculosis)‬
‭●‬ ‭This topic has a lot of strong opinions on either side‬

‭Related/Support readings in Chapter 1‬

‭●‬ ‭2.2.1 Federalism in Canada: The Constitution Act, 1867‬
‭●‬ ‭3.2 Role of the State‬
‭●‬ ‭3.3.2 Liberty‬
‭●‬ ‭3.6 Ethical Frameworks‬
‭●‬ ‭5.8 Role of Media‬
‭●‬ ‭5.9 Insurance, Elasticity and Moral Hazard‬
‭●‬ ‭8.1 Economic Analysis: Cost-effectiveness‬
 ‭‬
● ‭ .2 Screening‬
8
‭●‬ ‭8.2.1 Criteria for Screening‬
‭●‬ ‭8.2.2 Assessing Screening tests (test/truth)‬
‭●‬ ‭8.2.3 The Role of Prevalence‬

‭Agenda‬
‭●‬ ‭Context: screening and public policy‬
‭○‬ ‭How we decide what we screen and test for and who pays, etc.‬
‭●‬ ‭PKU – the Guthrie Test‬
‭●‬ ‭WHO: justification for screening‬
‭●‬ ‭Ontario Policy – criteria used for selecting tests‬
‭●‬ ‭Research Context: Incidental Findings & Actionability‬
‭●‬ ‭Ethical considerations: normality, eugenics, rights, the ”big 4”, human nature (heuristics &‬
‭Prospect Theory)‬
‭●‬ ‭Examples and applications‬

‭Learning Objectives‬
‭●‬ ‭To understand the origins of screen test success‬
‭●‬ ‭To summarize the ethical issues surrounding screening tests‬
‭●‬ ‭To identify the justifications for screening as identified by the WHO‬
‭●‬ ‭To identify how screening tests are selected in Ontario‬
‭●‬ ‭To differentiate between testing circumstances as part of clinical care and as part of research‬
‭●‬ ‭To define “incidental findings” and “actionability” and how they apply in research screening‬
‭●‬ ‭To understand how “normality” contributes to successes and drawbacks in screening tests‬
‭●‬ ‭To identify examples where screening tests are widely used in clinical practice and how positive‬
‭and negative results are interpreted‬

‭Genetic Screening & Testing in Infants‬

‭●‬ ‭Genetic screening and testing in infants in the context of Ontario‬

‭○‬ ‭Genetic screening and testing is similar across the country but there are differences‬
‭between provinces bc provinces have a say in what they spend their healthcare dollars on‬
‭-- but it is becoming a more of a NATIONAL & CONSISTENT approach‬

‭Genetic Tests have significant legal, social, ethical and public policy implications‬
‭●‬ ‭Genetic tests provide information and some level of entertainment (23 and me test kit)‬
 ‭ ‬ ‭Cool to see where you came from‬
○
‭○‬ ‭But also issues related health and healthcare‬
‭4 key issues (important considerations)‬
‭●‬ ‭Autonomy‬
‭○‬ ‭The ability to make decisions for yourself as an autonomous and educated human being‬
‭who has reached the age of majority and can make choices for themselves‬
‭●‬ ‭Confidentiality‬
‭○‬ ‭The right to confidentiality‬
‭○‬ ‭Even if you do get some of these tests done for health reasons or just out of interest, the‬
‭default is that your result should be confidential and you are the only person to have the‬
‭right to share it unless you have agreed otherwise‬
‭○‬ ‭Confidentiality is NOT the same as privacy‬
‭■‬ ‭Confidentiality = People are given information in the expectation that it will be‬
‭held in confidence. It is necessary usually to do their job‬
‭■‬ ‭Ex: if in a health care hospital setting, clinicians have access to your health‬
‭record and use that info to understand your background, comorbidities, and help‬
‭make the best case decisions‬
‭■‬ ‭Using it and keeping it in a confidential way‬
‭○‬ ‭Different than ANONYMOUS‬
‭■‬ ‭Anonymous is when your results are absolutely unable to be traced back to you‬
‭as an individual‬
‭●‬ ‭Privacy‬
‭○‬ ‭Privacy is another important consideration‬
‭○‬ ‭Privacy and confidentiality go rather hand-in-hand because privacy is essentially your‬
‭right to confidentiality‬
‭○‬ ‭Most of the legislation in Canada refers to privacy of information and protection of it as‬
‭opposed to confidentiality‬
‭○‬ ‭Privacy is more the actionable term in our ability to have information about us stored‬
‭safely and securely and used appropriately‬
‭○‬
‭●‬ ‭Equity‬
‭○‬ ‭Genetic tests also have significant social and ethical implications regarding equity‬
‭○‬ ‭A good deal of early genetic work was focused on white people and less research on‬
‭visible minorities‬
‭○‬ ‭It is important to offer genetic screening and genetic testing to EVERYONE regardless of‬
‭the background or origin status‬
‭○‬ ‭Different ethnic groups experience genetic illness differently -- some groups are unique to‬
‭specific illnesses (e.g. nescilamia? or tacsacticy?) where it is a ethnic linked genetic trait‬
‭as opposed to something that the general population can have‬
‭●‬ ‭These 4 considerations are important on their own, but they're even more important when you put‬
‭them together‬
‭○‬ ‭Like toppings on a sandwich‬
 ‭○‬ T ‭ hese considerations are combined with legal contexts of regulatory frameworks for‬
‭protection of those things, and social standards and social expectations regarding genetic‬
‭testing/screening‬
‭●‬ ‭Policy – consensus & critical‬
‭○‬ ‭Then are then of course parts that become public policy in terms of actual government‬
‭focused endeavors in this realm‬
‭○‬ ‭The policy realm has a lot of BOTH consensus and critical approaches to genetic‬
‭screening of health care‬
‭○‬ ‭Consensus = the nuts and the bolts of how a genetic testing policy happens‬
‭■‬ ‭would include things like:‬
‭■‬ ‭What tests are we covering?‬
‭■‬ ‭Is it males or females that are being tested?‬
‭■‬ ‭Is it all age groups?‬
‭■‬ ‭How will we return the results?‬
‭■‬ ‭What will we do with the data‬
‭■‬ ‭Basically all of the items you would think about that you need to keep your‬
‭program running‬
‭○‬ ‭Critical = focused more on the social, ethical implications‬
‭■‬ ‭Include:‬
‭■‬ ‭Are we testing all ethnic groups?‬
‭■‬ ‭Are women and men fairly treated in this realm?‬
‭■‬ ‭What about children?‬
‭ ‬ ‭Ethics‬
●
‭○‬ ‭The ethical considerations‬
‭○‬ ‭Is it ethical to test for something that you can actually do something about?‬
‭○‬ ‭Or is it ethical to identify traits in people with no specific traits in mind?‬
‭○‬ ‭There are these considerations‬

‭Key Terms‬
‭●‬ ‭Important terms for this content!‬
‭●‬ ‭Screening vs Testing‬
‭○‬ ‭Recall: we talked about this with tuberculosis‬
‭■‬ ‭Context varies‬
‭■‬ ‭In TB, about trying to find communicable disease in a population‬
‭■‬ ‭This case is different, looking at the genetic basis for illness or possible illness in‬
‭specific populations and for specific purposes‬
‭○‬ ‭Concept is the same for genetic screening and testing‬
‭■‬ ‭The ACTIVITY/concept is the same, but the context is different‬
‭●‬ ‭Genetic Screening:‬‭performed in the general population; early detection, monitor risk‬
‭○‬ ‭Similar to disease screening‬
‭○‬ ‭It is performed in the general population‬
‭○‬ ‭The intention is to provide early detection of disease or possible disease, and monitor risk‬
‭○‬ ‭You go LOOKING for risk factors = screening‬
 ‭●‬ G ‭ enetic Testing‬‭: Applies to individuals who are seen as having a higher probability of having a‬
‭particular condition; determine presence/absence‬
‭○‬ ‭Once you have SYMPTOMS, you are no longer screening you are TESTING‬
‭○‬ ‭Once determined that someone has a higher likelihood of having a particular condition‬
‭(i.e. screening), then you set out to actually make sure beyond a reasonable doubt or to‬
‭the best of sciences ability whether someone actually has a condition, yes or no‬
‭●‬ ‭Specificity vs. Sensitivity‬
‭○‬ ‭Our reliance on genetic screening/testing, whether it becomes part of healthy public‬
‭policy or just public health policy, are the concepts of specificity and sensitivity‬
‭○‬ ‭This is something you can study in biostatistics and epidemiology‬
‭○‬ ‭The distinction between the two is really important!!!‬
‭●‬ ‭Specificity‬‭: Is the ability to correctly rule out disease‬
‭○‬ ‭The statistical reliability or ability of a genetic test/genetic screening instrument to‬
‭correctly‬
‭●‬ ‭Sensitivity‬‭: Is the ability to correctly pick up positive cases‬
‭○‬ ‭The statistical reliability of genetic tests to correctly identify cases where the person is‬
‭positive‬

‭Sensitivity & Specificity‬

‭●‬ ‭Truth = the status of an individual who has undergone genetic testing/screening‬
‭○‬ ‭They would either find themselves in a binary disease state (either have disease OR don't‬
‭have disease)‬
‭○‬ ‭Binary status -- either have a condition or don't have a condition‬
‭○‬ ‭Truth is typically ruled out through testing and by actually finding out what is going on‬
‭○‬ ‭When screening, we are looking for risk factors but we want to make sure that the‬
‭screening test is consistent and coherent with the ACTUAL reality or the TRUTH‬
‭○‬ ‭Cases of people with either:‬
‭■‬ ‭With disease‬
‭■‬ ‭Without disease‬
‭■‬ ‭People who definitely don't have a disease and they aren't carriers‬
‭●‬ ‭Specific‬‭: ability to RULE out disease (i.e. D) - ability of the test or to obtain normal range or‬
‭negative results for a person who does not have a disease‬
 ‭○‬ A ‭ person who does NOT have a disease and the test result shows that they don't have the‬
‭disease‬
‭○‬ ‭Ex: COVID tests‬
‭■‬ ‭Covid tests in their early days more very specific (and in some case sensitive)‬
‭and now that COVID has mutated (and if using expired tests), the ability to be‬
‭specific is often not very good‬
‭■‬ ‭Can't rely on an expired test like covid always to be specific because it often has‬
‭people with the disease, but identifies them as being negative (i.e. false negative)‬
‭○‬ ‭True negative = D‬
‭■‬ ‭People who are legitimately non-carriers of a disease and the test result‬
‭corresponds with that‬
‭■‬ ‭This is SPECIFIC‬
‭○‬ ‭A specific test will always show NON-DISEASE and NON-DISEASE in the TEST‬
‭RESULT‬
‭●‬ ‭Sensitive‬‭: ability to ID positive cases (i.e. A) - proportion of true positives tests out of all patients‬
‭with a condition‬
‭○‬ ‭Know how many POSITIVE cases there are‬
‭○‬ ‭They have the condition and the test will ALWAYS show that this is the case‬
‭○‬ ‭Ex: X-Ray or any other radiographic exam‬
‭■‬ ‭A really good example of a sensitive test‬
‭■‬ ‭Obvious break in a bone or tumor can be seen and identified as such‬
‭ ‬ ‭Ex: Breast screening‬
●
‭○‬ ‭Different types of breast tissue are prone to not being specific or not being sensitive‬
‭○‬ ‭The screening is mammography‬
‭○‬ ‭Mammography = done on anyone now over 40 (not limited to females)‬
‭○‬ ‭Not very specific for people with specific types of breast tissue (categorized as A, B, C,‬
‭D -- from dense to fatty)‬
‭○‬ ‭If you have dense tissue you need to go back for another test (e.g. ultrasound, CT) that is‬
‭more specific and able to rule out disease‬
‭●‬ ‭IDEALLY, the best screening test will be both SPECIFIC and SENSITIVE!‬
‭○‬ ‭Some conditions we don't "care" if they are both (bc not required)‬
‭○‬ ‭Ex: if you just want to make sure that people DON'T have COVID, then you just have to‬
‭be specific‬
‭■‬ ‭Not necessarily interested in identifying people who do‬
‭○‬ ‭In communicable disease, a sensitive test is important because we want to know who is‬
‭sick so we can quarantine them and keep them away‬
‭■‬ ‭The specific part of the test will help identify the inability to have disease‬
‭spreading throughout the community‬

‭Predictive Value‬
‭●‬ ‭In biostatistics and epidemiology, sensitivity and specificity are a lot more common than the‬
‭diagram shown previously‬
 ‭○‬ H ‭ ow we gauge the success of any genetic screening/testing is its ability to identify the‬
‭positive cases where required and the identification of negative cases where required, and‬
‭sometimes both -- done via the PPV or NPV of a test‬
‭●‬ ‭Positive Predictive Value (PPV‬‭) is a ratio of the true positives (numerator) relative to true/false‬
‭positives (denominator)‬
‭○‬ ‭i.e. (total number of A)/(total number of A + B)‬
‭○‬ ‭Positive predictive value = look at the POSITIVE row‬
‭○‬ ‭The higher the number of true positives (compared to false positives), the BETTER the‬
‭Positive Predictive Value‬
‭○‬ ‭A ratio of how well a test does at being positive in its prediction‬
‭●‬ ‭Negative Predictive Value (NPV)‬‭is a ratio of the true negatives (numerator) relative to true/false‬
‭negatives (denominator)‬
‭○‬ ‭i.e. (D / [C+D])‬
‭○‬ ‭The opposite of PPV‬
‭●‬ ‭Important because if you have a test that is not doing a good job at being reliable in showing true‬
‭positive's, there is often no value in using it‬
‭○‬ ‭Or maybe society in the practice of medicine has been using a specific screening test for a‬
‭long time and its predictive value is 50%, but with improvements in science and‬
‭technology, another screening test will allow you to improve that to 70-75% and then you‬
‭might switch tests‬
‭○‬ ‭Sometimes a poor positive predictive value is better than nothing because you don't have‬
‭anything, but if you are making a choice as a policy maker, you want to look at what is‬
‭the BEST accurate test that we have that has the best positive predictive value, or best‬
‭negative predictive value because some conditions are more aligned with that‬
‭●‬ ‭Improvement is relative to the costs that is present‬
‭○‬ ‭If science could come up with a really good way to improve mammography screening for‬
‭breast cancer, to improve the NPV (specificity) or PPV (sensitivity) and it costs millions‬
‭more, the new test would theoretically not be economical/more efficient than the system‬
‭that we have‬
‭○‬ ‭Which is why the list of terms at the beginning included "cost-effectiveness analysis"‬
‭○‬ ‭The purpose of predictive value in policy selection is the most economical to do the best‬
‭job (i.e. want to do the job without breaking the bank)‬
‭○‬ ‭These are data that a policy maker would use when trying to decide whether they should‬
‭adopt a certain genetic screening/genetic test procedure‬
‭●‬ ‭Disease prevalence‬‭in a population affects PPV and NPV. When a disease is highly prevalent, the‬
‭test is better at ‘ruling in' the disease and worse at ‘ruling it out.‬
‭○‬ ‭Disease prevalence is really important in the application of screening and testing whether‬
‭it's a disease that is congenital, chronic, or communicable‬
‭○‬ ‭The predictive value is affected by the disease prevalence in the community‬
‭○‬ ‭When a disease highly prevalent disease:‬
‭■‬ ‭Better at ruling IN the disease‬
‭■‬ ‭Worse at ruling OUT the disease‬
‭■‬ ‭Therefore, better off with a test that is more SPECIFIC than SENSITIVE‬
‭○‬ ‭Ex: COVID -- when large numbers of cases are circulating in the community‬
 ‭ ‬ ‭It is better to use a test that rules it OUT (specific test)‬
■
‭■‬ ‭Specific tests are more important to identify "having disease" vs "ruling it out"‬
‭ ‬ ‭COVID testing program and the rationale behind it‬
●
‭○‬ ‭Scientists have learned the natural history of disease and have a better understanding of‬
‭how it behaves, the natural life cycle, etc.‬
‭○‬ ‭Since we KNOW MORE, we don't have to test it like we did 3-4 years ago‬
‭○‬ ‭It is a policy choice‬

‭The Concept of Normality‬

‭●‬ ‭Not only do you need tests that are sensitive and specific also have to consider how good of a job‬
‭they do at being positive predictors and negative predictors and what is normal?‬
‭●‬ ‭Requires determination of what is normal or abnormal.‬
‭○‬ ‭When testing/screening for a condition there is a cultural scientific assumption of what is‬
‭normal/desirable and abnormal/undesirable‬
‭○‬ ‭Ex: we do not want ppl to have COVID, we want people to avoid it and not have it‬
‭○‬ ‭So there is this decision made which is sometimes a POLICY decision on what is‬
‭normal?‬
‭○‬ ‭Sometimes, normal = societal or cultural idea‬
‭○‬ ‭Then it is implemented as policy‬
‭○‬ ‭Sometimes it is strictly a policy choice‬
‭■‬ ‭The government can decide what level of "x" in the community is normal or‬
‭tolerable disease, etc.‬
‭○‬ ‭Often, normal is determined through social and cultural discourse -- academics contribute‬
‭a lot to this area as well through research‬
‭○‬ ‭People who work in clinical and moral ethics contribute a lot to the concept of normality‬
‭○‬ ‭ESSENTIALLY: no test and PPV/NPV of a test can exist UNLESS you determine a‬
‭binary position of what is normal & what is not normal‬
‭○‬ ‭Note: the concept of normal changes overtime‬
‭■‬ ‭Ex: how children w/ autism are treated in the school system‬
‭■‬ ‭Has vastly changed compared to the past‬
‭■‬ ‭Now = inclusion‬
‭■‬ ‭Past = exclusion‬
‭■‬ ‭Normal changes based on the social and moral discourses‬
‭●‬ ‭Once determined, you have implications re: preventing birth of ‘abnormal children’ or‬
‭children or adults that become ‘defective’ due to a disability acquired in one’s lifetime‬
‭●‬ ‭What is defined as normal, and who judges?‬
‭○‬ ‭Normality also has a lot of ethical issues -- WHO is normal, WHAT is normal, WHO gets‬
‭to decide?‬
‭○‬ ‭It is a lot like ableism (recall)‬
‭■‬ ‭Who are we to say just bc the WHO definition of health is "absence of disease or‬
‭infirmity"‬
‭■‬ ‭It is not necessarily true that other ppl who don't meet that definition aren't living‬
‭a good life‬
 ‭○‬ Y ‭ ou could discuss and debate normality for a long time and never entirely achieve‬
‭consensus -- this is why policy decisions are important‬
‭●‬ ‭Eugenics (i.e. good birth) was postulated in the 1880s by Charles Darwin's cousin Francis‬
‭Galton, who hoped that this would improve humanity‬
‭○‬ ‭Eugenics = good birth‬
‭○‬ ‭Galton first proposed the idea of eugenics -- that you could prevent certain diseases from‬
‭becoming prevalent or even existing in society and that would be better for humanity‬
‭○‬ ‭His intentions may have been good but had terrible effects‬
‭ ‬ ‭Selective breeding had been used to “improve” animals and plants; its extension to humans‬
●
‭is far more controversial, particularly given its association with genocide under the Nazis‬
‭and forced sterilization‬
‭○‬ ‭Normality is also fluctuating in the context of agricultural improvement‬
‭■‬ ‭We can use different cattle to selectively improve animals‬
‭■‬ ‭Or use for plants‬
‭■‬ ‭Holstein dairy cows seen today is the produce of selective breeding across many‬
‭years to get the best milk makers‬
‭■‬ ‭BUT, when you make the best milk maker in a Holstein, you don't make a good‬
‭beef producing cow‬
‭○‬ ‭The same is done with plants‬
‭■‬ ‭If one corn plant has high yields and another corn plant tolerates colder weather‬
‭■‬ ‭Selective breeding is improving‬
‭■‬ ‭Sometimes you don't have a baseline of normal in selective breeding situations‬
‭but in the human context it becomes far more complicated‬
‭●‬ ‭https://ethics.gc.ca/eng/documents/incidental_findings_en.pdf‬

‭‬ h
● ‭ ttps://www.nature.com/scitable/topicpage/human-testing-the-eugenics-movement-and-irbs-724/‬
‭●‬ ‭Ex: In WW2 Eugenics became an outlet for a lot of hatred and persecution for many‬
‭○‬ ‭German experiment in WW2‬
‭●‬ ‭In the USA, there have been a number of eugenics movement that were attempted in the US‬
 ‭‬ T
● ‭ hey have all been looked upon in history as never a good thing‬
‭●‬ ‭The quality of the human population for desirable traits -- similar to animal breeders with‬
‭agriculture‬
‭●‬ ‭Ex: Davenport founding the Eugenics record office laboratory‬
‭○‬ ‭About improving quality‬
‭○‬ ‭Regrettably turned into a movement where a number of members of society were‬
‭medically treated so they were unable to have children, certain families with certain traits‬
‭were discouraged form having children‬
‭○‬ ‭The whole idea was to remove certain genes from the population‬
‭○‬ ‭Many of these policies included involuntary sterilization or institutionalization‬
‭●‬ ‭Identifying normal leads down ethical rabbit holes‬
‭○‬ ‭There are a whole load of ethical considerations and problems associated with race‬
‭hygiene‬
‭○‬ ‭Perhaps may have started off as innocent and hopefully helping society but can do the‬
‭opposite‬

‭When is Screening Justified ? (WHO, 1968)‬

‭●‬ ‭Once we have decided what normal is, we can screen for it‬
‭○‬ ‭But screening isn't always the option that you want‬
‭○‬ ‭Screening is not always an answer‬
‭●‬ ‭WHO‬
‭○‬ ‭Because screening isn't always an answer, the WHO developed a set of policies in 1968‬
‭to help us to identify times where screening is JUSTIFIED‬
‭○‬ ‭This rolls in ethical considerations, legal ramifications, social and political components,‬
‭considers autonomy (ability of people to make decisions for themselves), the welfare of‬
‭the person‬
‭○‬ ‭Recall: principlism‬
‭■‬ ‭i.e. autonomy, beneficence, non-maleficence‬
‭■‬ ‭All of those ethical concepts show up when we talk about genetic screening and‬
‭genetic testing -- and they also appear here in this list of times when screening is‬
‭justified‬
‭●‬ ‭When is Screening Justified (WHO, 1968)‬
‭○‬ ‭Condition is an important health problem‬
‭■‬ ‭Screen when the condition is an important health problem‬
‭■‬ ‭Important is a subjective label but important meaning volumes, prevalence of‬
‭cases of a health problem, extensive cost to HC system, increase disability in the‬
‭population, etc.‬
‭■‬ ‭The condition has to be declared an important health problem but how you define‬
‭important is very fluctuating and variable‬
‭○‬ ‭Accepted treatment for patients with recognized disease‬
‭■‬ ‭The condition might be important and you can screen for it, but it is not ethical to‬
‭go looking for something when you can't do anything about it‬
‭■‬ ‭If there is no treatment, there's no value other than causing emotional and‬
‭psychological stress‬
 ‭■‬ T ‭ his is one of the KEY factors Ontario has incorporated into what does it screen‬
‭for in the nursery bc there is a lot of conditions (esp. rare genetic conditions) that‬
‭we can screen for and test, but there is no acceptable treatment‬
‭■‬ ‭What are you supposed to do with conditions that will not manifest themselves‬
‭till later in life but there is no treatment right now (e.g. Alzheimer's)‬
‭■‬ ‭Could theoretically come up with a test for Alzheimer's screening but not going‬
‭to do it under older (60s or 70s), but if there's no treatment that results in an‬
‭ethical dilemma‬
‭■‬ ‭Have the right to now vs. why would you want to know if you can't do‬
‭anything about it‬
‭○‬ ‭Facilities for diagnosis and treatment‬
‭■‬ ‭Need to have facilities for diagnosis and treatment‬
‭■‬ ‭Note: this list is linear -- identify the condition, need to treat it, and need to be‬
‭able to diagnose it‬
‭■‬ ‭PPV or NPV = diagnosing‬
‭■‬ ‭And be able to treat it‬
‭○‬ ‭Recognizable latent or early symptomatic stage‬
‭■‬ ‭Can identify it before it happens‬
‭■‬ ‭Or we can identify it very early when it starts to show symptoms‬
‭■‬ ‭Once you go from being latent to showing symptoms it's no longer screening, it‬
‭is testing‬
‭○‬ ‭Suitable test or exam‬
‭■‬ ‭Need a suitable test or exam to be able to go looking for it‬
‭■‬ ‭Test has to be reliable and specific and sensitive‬
‭○‬ ‭Test is acceptable to the population‬
‭■‬ ‭You can test and screen for colon cancer 2 diff ways once is very invasive‬
‭(colonoscopy), other is fecal occult blood test (poo on a stick -- far less invasive‬
‭and accessible to population)‬
‭○‬ ‭Natural history of disease is known‬
‭■‬ ‭Fact finding and understand where things are going‬
‭○‬ ‭Agreed on policy to who can be treated‬
‭■‬ ‭Can everybody be treated? If not, why?‬
‭■‬ ‭Ex: when ppl have a condition that can be treated by experimental/new drugs‬
‭■‬ ‭Typically they have been approved but rlly expensive‬
‭■‬ ‭Or approved for other conditions and clinicians use off-label‬
‭■‬ ‭All about who can be treated‬
‭○‬ ‭Case finding is economically balanced in relation to the possible expenditure on care‬
‭■‬ ‭This is COST-EFFECTIVENESS ANALYSIS‬
‭■‬ ‭Really important when picking a test‬
‭■‬ ‭Ex: colonoscopy vs poop on a stick‬
‭■‬ ‭Colonoscopy = $800 for hospital time‬
‭■‬ ‭Poop on a stick = $50‬
‭■‬ ‭The second one is a good test that works and is also economically a‬
‭better choice for an uncomplicated condition‬
 ‭○‬ C
‭ ase finding is a continuing process and not a once and for all (Wilson and Junger,‬
‭1968)‬
‭■‬ ‭It is an ethical requirement to not just go looking for condition in the year 2024‬
‭and then just stop because it excludes people in the future‬
‭■‬ ‭Want to keep adding it as a continuing part of your health care system and not‬
‭just point in times‬
‭■‬ ‭Point in times are appropriate for communicable disease outbreaks where case‬
‭finding is necessary, but as for genetic screening it is typically not‬

‭Early Success in Genetic Screening Tests‬

‭●‬ ‭Guthrie Test (Dr. Robert Guthrie, 1916-95) for Phenylketonuria (PKU) – ingestion of‬
‭phenylalanine (Phe) would cause brain damage; correctable with diet; test was simple and‬
‭inexpensive‬
‭○‬ ‭Dr. Robert Guthrie -- the father of genetic screening‬
‭○‬ ‭Provided us with our earliest successes in application of genetic screening in the HC‬
‭system‬
‭○‬ ‭PKU is a condition that can cause brain damage if you ingest phenylalanine (often found‬
‭in processed foods)‬
‭○‬ ‭If you identify these ppl with PKU, can keep Phe out of their system and cure a problem‬
‭●‬ ‭"Heel Prick" test - The original test has been replaced by mass-spectroscopy measurement of Phe‬
‭concentration.‬
‭○‬ ‭When born get heel prick test, cards the blood, dry the blood and do tests with it‬
‭○‬ ‭This is what used to be done, now it is much improved‬
‭○‬ ‭Now, can measure Phe concentration and look for a number of different conditions in this‬
‭heel prick test for newborns‬
‭●‬ ‭Children in families at risk for PKU may also be screened by prenatal PCR-based DNA tests for‬
‭the PKU-related alleles themselves.‬
‭https://www.mun.ca/biology/scarr/PKU_diagnosis_&_treatment.html‬

‭Criteria Used in Ontario to Choose Screening Methodologies…1‬

‭●‬ ‭There is a list of 9 criteria that the Ministry of Health uses when selecting its screening‬
‭methodologies for health care -- overlap with WHO list‬
‭1.‬ ‭Identify Objective:‬
‭○‬ ‭clear reason for genetic screening should be defined (e.g., is the goal medical‬
‭intervention, reproductive planning, and/or research?)‬
‭○‬ ‭What is your clear reason for genetic screening?‬
‭○‬ ‭There must be an objective‬
‭2.‬ ‭Feasibility‬
‭○‬ ‭Needs to be done in an integrated program; facilities, resources, and personnel should be‬
‭available to educate/counsel and confirm diagnosis, treatment and outcomes evaluation‬
‭○‬ ‭In every hospital in Ontario that is triage level they are going to have a genetic medical‬
‭genetics department where they deal with this -- experts, counsellors, etc.‬
‭3.‬ ‭Propensity:‬
 ‭○‬ H ‭ igh-risk individuals should be screened/detected by a simple, inexpensive test with high‬
‭sensitivity, specificity, and predictive efficiency (elevated risk)‬
‭○‬ ‭Really important!‬
‭○‬ ‭Essentially a proportional approach to doing something relative to risk‬
‭○‬ ‭You don't want to or need to go our and look for everybody and test/screen all of them‬
‭○‬ ‭Screen/test should be relative to age, gender, exposures, etc.‬
‭○‬ ‭Ex: Ontario has 4 screening programs‬
‭■‬ ‭Anyone who has smoked a cig daily for 20 years is eligible for the lung cancer‬
‭screening program‬
‭■‬ ‭Targeting high-risk individuals‬
‭○‬ ‭Propensity is targeting HIGH RISK people with tests that work‬
‭4.‬ ‭Significance of Disease:‬
‭○‬ ‭The condition should be medically significant in the population under consideration.‬
‭○‬ ‭An ethical problem in medical genetics and genetic screening‬
‭■‬ ‭There are a large number of rare diseases and rare diseases only affect a small‬
‭proportion of the population, there is far less research on them, and since they are‬
‭such a small prop, a lot of the tests don't screen for them bc deemed not‬
‭medically significant‬
‭■‬ ‭It might be debilitating in the people who have the condition but not widespread‬
‭enough‬
‭5.‬ ‭Benefit of Treatment:‬
‭○‬ ‭Goal of screening is treatment of disease & thus affected individuals should benefit from‬
‭medical intervention initiated on the basis of the screening procedure. Agreement must‬
‭exist regarding type of treatment and who to treat.‬
‭○‬ ‭Treatment should WORK‬
‭6.‬ ‭Consent‬
‭○‬ ‭Individuals should be informed of the goals, operation, and implications of the screening‬
‭program; right to refuse without prejudice.‬
‭○‬ ‭Individuals should be autonomous and consent for themselves to be informed of the risks‬
‭and benefits‬
‭○‬ ‭They can refuse without prejudice‬
‭■‬ ‭E.g. they can refuse getting screen for breast cancer knowing that it runs in their‬
‭family, but if they do develop it, it doesn't mean they can't get treated by that‬
‭doctor or be treated any different‬
‭○‬ ‭Right to ignorance‬
‭7.‬ ‭Regulation‬
‭○‬ ‭The outcome/impact of screening programs should be monitored and evaluated; program‬
‭should be modified if required.‬
‭○‬ ‭If new scientific knowledge is found should modify those programs as required‬
‭○‬ ‭Recall: Walkerton‬
‭8.‬ ‭Values‬
‭○‬ ‭Individual values and rights must be protected.‬
‭○‬ ‭Religious reasons, etc.‬
‭○‬ ‭Can refuse screening due to beliefs‬
 ‭9.‬ ‭Cost‬
‭○‬ ‭The cost of the tests is not prohibitive and meets cost-benefit analysis.‬

‭When?‬
‭●‬ ‭Prenatal‬
‭●‬ ‭Newborn‬
‭●‬ ‭Among various members of the population (i.e. late onset like Huntington’s)‬
‭○‬ ‭Can screen for older people (40+) -- e.g. breast cancer‬
‭○‬ ‭Huntington's -- can identify that you have it and it will be late onset but treatment avail in‬
‭early stages to slow it down‬
‭●‬ ‭Cancer Care Ontario‬
‭○‬ ‭4 screening programs at Cancer Care Ontario‬
‭○‬ ‭Breast screening, lung cancer screening, colon cancer screening, etc.‬
‭●‬ ‭Once symptoms appear, no longer screening‬
‭●‬ ‭Under-writing: evaluates riskiness of a proposed insurance policy‬
‭○‬ ‭More of an issue in America‬
‭○‬ ‭When trying to get HC, and have an underlying medical condition/problem, they are‬
‭excluded from coverage in the policy‬
‭○‬ ‭Underwriting is part of insurance provision in the US‬
‭○‬ ‭It is part of the insurance process in Canada for more private insurance (e.g. life‬
‭insurance)‬
‭○‬ ‭Medical questions will identify issues that evaluate your risk relative to proposed‬
‭insurance policy‬
‭○‬ ‭Often, life insurance doesn't have a lot of underwriting in younger people‬
‭■‬ ‭Life insurance usually stops once you turn 80 and you can't get it back most of‬
‭the time bc the risk of you needing it would be sooner rather than later‬
‭●‬ ‭Propensity and availability of treatment‬
‭○‬ ‭Propensity = the high risk target‬
‭○‬ ‭Targeting high risk people and having treatment ready to get people at an early age of‬
‭illness is really important part of the policy in Ontario‬
‭●‬ ‭As condition of employment? Discrimination‬
‭○‬ ‭Is it important to ask for genetic screening to be done as a condition of employment?‬
‭○‬ ‭Ex: working in coal mine and susceptible to a certain lung condition‬
‭○‬ ‭But can also lead to cases of discrimination in the workplace and unfair hiring practices‬
‭due to genetic "baggage"‬
‭ ‬ I‭ n Ontario, there is PRENATAL SCREENING and NEWBORN SCREENING‬
●
‭●‬ ‭Prenatal screening‬
‭○‬ ‭Ethical red herring‬
‭○‬ ‭Can find out before baby is born if your baby is likely to have‬
‭■‬ ‭Down Syndrome;‬
‭■‬ ‭Edwards Syndrome‬
‭○‬ ‭Non-invasive -- everyone gets ultrasound‬
‭○‬ ‭Amniocentesis -- but if you are at higher risk, you can have an amniocentesis‬
‭■‬ ‭Test amniotic fluid and test it for more specific and sensitivity‬
‭○‬ ‭Can also find out sex through ultrasound‬

‭●‬ ‭Newborn screening‬

‭○‬ ‭E.g. Guthrie test‬
 ‭○‬ ‭Newborn Screening Ontario website‬
‭■‬ ‭Can screen for a WIDE range of diseases, conditions, deficiencies, etc.‬
‭■‬ ‭Tells you incidence, marker measured, what screening can prevent, treatment,‬
‭etc.‬
‭■‬ ‭The website alone meets the standards for screening and the policy for selecting‬
‭tests and screens in Ontario are all in the communication‬
‭○‬ ‭The policy formation part is important to consider‬
‭■‬ ‭But actual policy action and implementation is also going to include those values‬
‭of planning, communication, evaluation, etc.‬

‭Screening Context “Rights”‬

‭●‬ ‭The Right to Remain Ignorant:‬
‭○‬ ‭Allowed to not participate in screening -- right to refuse‬
‭■‬ ‭E.g. can skip mammography‬
‭○‬ ‭If you do participate in screening you have the right to remain ignorant‬
‭○‬ ‭Genetic information does not affect only the person who had the test‬
‭○‬ ‭Who should receive such information?‬
‭●‬ ‭The Right of Privacy and the Right to Know:‬
‭○‬ ‭Right to know genetic information about themselves‬
‭○‬ ‭Lack of knowledge may lead to children not being born because parents fear they have a‬
‭gene they do not, while others may have children believing they don’t carry the‬
‭condition, but they actually do‬
‭○‬ ‭Have the right to know‬
‭○‬ ‭When you do find out, through the medical process you have the right to privacy (nobody‬
‭needs to find out unless you agree to share)‬

‭Research - Screening “Wiggle Room”: Incidental Findings‬

‭●‬ ‭There is of course a disclaimer when it comes to the right to know‬
‭○‬ ‭Clinical research protocols for the betterment of society are very rigorous, tightly‬
‭designed and positivist‬
‭○‬ ‭So the inclusion/exclusion criteria for the study is very rigorous‬
‭○‬ ‭Rapid technological advances, the evolution of research capabilities, large volumes of‬
‭data, and the push for innovation contribute to increasing the probability of incidental‬
‭findings in research involving humans.‬
‭●‬ ‭“Incidental Finding”‬‭:‬
‭○‬ ‭discovery about participants during the course of research, but is not included in the study‬
‭objectives‬
‭○‬ ‭Through the process of a clinical trial, may find out health information about a participant‬
‭that is incidental or secondary to the actual study itself‬
‭○‬ ‭Not part of the overall study but found throughout the course of the study‬
‭○‬ ‭Ex: study on follow up to Breast Cancer to see change in biomarkers‬
‭■‬ ‭But unintendedly find new cases of breast cancer‬
‭■‬ ‭This is incidental finding‬
‭●‬ ‭“Material”‬
 ‭○‬ i‭.e. significant welfare implications for the participant or prospective participant (TCPS 2,‬
‭introduction to Article 3.4)‬
‭○‬ ‭If the incidental finding is of material nature, the Tri-Council Policy Statement is the‬
‭guidance document for research ethics in Canada‬
‭○‬ ‭Any implications related to welfare for the participant or prospective participant should‬
‭be identified‬
‭○‬ ‭This includes:‬
‭■‬ ‭information they find out about you as an individual‬
‭■‬ ‭Information for groups of people‬
‭■‬ ‭E.g. if a drug trial is not good in ethnic group "X"‬
‭■‬ ‭E.g. or if there is a side effect in a specific population that is shared‬
‭○‬ ‭Basically, there's a set of guidance regarding how that must be shared and when it must‬
‭be shared‬
‭●‬ ‭Examples:‬
‭○‬ ‭Unexpected mass on CT or MRI‬
‭○‬ ‭Genome sequences that reveals additional genetic variation for a participant, such as high‬
‭risk for cancer‬
‭○‬ ‭Discovery of physical abuse or suicidality in studies unrelated to those phenomena‬
‭ ‬ ‭Incidental Findings can also affect non-participant‬
●
‭○‬ ‭https://rarediseases.info.nih.gov/diseases/9728/myotonic-dystrophy-type-2‬

‭Research: Reporting if Valid, Significant & Actionable‬

‭●‬ ‭In research, you MUST report incidental findings if they are valid, significant/material, actionable‬
‭○‬ ‭As required by the Tri-Council Policy Statement‬
‭●‬ ‭According to the TCPS, a Material Finding must be (should be all 3):‬
‭○‬ ‭Valid‬
‭■‬ ‭researchers have verified the accuracy/precision of the finding & confirmed that‬
‭the finding is not an artefact of the research methodology.‬
‭■‬ ‭Researchers are certain that they have verified the finding‬
‭○‬ ‭Significant‬
‭■‬ ‭findings are potentially important to disclose to the participant, given that they‬
‭may significantly affect the participant’s welfare (health or otherwise).‬
‭○‬ ‭Actionable‬
‭■‬ ‭participant can initiate an action to remove or help manage the risk to his/her‬
‭welfare, and/or can use this information to take steps that may result in the‬
‭research participant’s or relative’s benefit‬
‭■‬ ‭Participant can actually do something to help manage risk‬
‭■‬ ‭Balance between identifying an incidental finding that might be valid but if you‬
‭can't do anything about it, given the stage of science, then it doesn't have to be‬
‭disclosed‬
‭●‬ ‭https://ethics.gc.ca/eng/documents/incidental_findings_en.pdf‬
‭●‬ ‭The right to know, the right to remain ignorant, and the right to privacy are all key tenants of‬
‭genetic policy in Canada‬
 ‭○‬ S ‭ ometimes research studies (clinical trials) can act like screening enterprises and they‬
‭uncover things through research on a different problem and thus required to report if they‬
‭are INCIDENTAL findings and they are VALID, SIGNIFICANT, and ACTIONABLE‬
‭○‬ ‭The TCPS calls these "material findings"‬
‭ ‬ ‭Occurs in the course of health care anyway (part of healthcare)‬
●
‭○‬ ‭Incidental findings in healthcare will happen as a matter of course‬
‭○‬ ‭In research however, because you're not actively providing health care services (instead‬
‭running a trial), it has to be valid, significant, and actionable‬

‭Ethical Principles‬
‭●‬ ‭Related to both ethical review of clinical trial research and normal practice of medicine are the‬
‭ethical principles of principlism‬
‭○‬ ‭Important in setting policy AND also implementing policy and making it actionable‬
‭every day‬
‭○‬ ‭These principles are key when sharing information that comes about through genetic‬
‭screening/testing‬
‭1.‬ ‭Respect:‬
‭○‬ ‭individuals should be treated as autonomous agents, and that persons with diminished‬
‭autonomy are entitled to protection.‬
‭○‬ ‭In the course of research, people with diminished autonomy that we focus on are‬
‭incarcerated individuals, children, and First Nations‬
‭○‬ ‭People who aren't autonomous or autonomy has been restricted in some way are entitled‬
‭to protection‬
‭2.‬ ‭Beneficence:‬
‭○‬ ‭do no harm, maximize possible benefits, and minimize possible harms.‬
‭○‬ ‭Should refer back to the WHO definitions of when you should to screening‬
‭3.‬ ‭Non-Maleficence:‬
‭○‬ ‭prevent agents of harm‬
‭4.‬ ‭Justice:‬
‭○‬ ‭fair treatment of all persons; sharing of burdens and benefits‬
‭○‬ ‭Clearly, there is no one “correct” policy..‬
‭■‬ ‭As justice and intersectionality have lots of manifestations in society‬
‭5.‬ ‭Autonomy‬
‭○‬ ‭An overarching principle‬
‭○‬ ‭People are individuals and if they have reached the age of majority they should be able to‬
‭make their own decisions‬

‭Minimizing Harm‬
‭●‬ ‭Minimizing harm = non-maleficence and beneficence‬
‭○‬ ‭Screening is never fool proof, which is why we move to testing when we're not sure‬
‭○‬ ‭But sometimes there are confounders and other factors‬
‭●‬ ‭Potential downsides may include:‬
‭○‬ ‭Test interpretation:‬
 ‭■‬ T ‭ ests, aimed at healthy people at high risk (e.g. due to family history) are hard to‬
‭interpret since many conditions are multifactorial (i.e. so many genes and so‬
‭many environmental factors)‬
‭■‬ ‭Healthy people at high risk = propensity is high‬
‭■‬ ‭Society and people within society are complex so it is hard when you are well‬
‭and not showing any symptoms to rely on tests‬
‭■‬ ‭Recall: this connects back to the importance of predictive value and specific and‬
‭sensitivity in testing‬
‭○‬ ‭Lack of options to treat.‬
‭■‬ ‭There can be a long lag time between linking a gene mutation with a disease and‬
‭developing effective à utilitarian arguments and cost-benefit questions.‬
‭■‬ ‭You can screen for something but a long time lag identifying disease and then‬
‭developing effective treatment‬
‭■‬ ‭Nothing you can do about it so what's the value in doing that?‬
‭ ‬ ‭Danger to employment and insurance‬
○
‭■‬ ‭Some conditions make people vulnerable to illness getting a disease‬
‭■‬ ‭Certain workplaces can make that worse‬
‭○‬ ‭Psychological impact:‬
‭■‬ ‭anxiety over the results, survivor’s guilt, fears of discrimination and social‬
‭stigmatization.‬
‭■‬ ‭Sometimes these impacts may outweigh the benefits of testing‬
‭■‬ ‭Ethical/psychological component of screening‬
‭■‬ ‭The psychological impact is not a consistent value across individuals which is‬
‭why we have the right to know and the right to remain ignorant because different‬
‭people have different perceptions of risk‬

‭Moral Hazard‬
‭●‬ ‭Moral Hazard‬‭: lack of incentive to guard against risk where one is protected from its‬
‭consequences, e.g. by insurance‬
‭●‬ ‭In the context insurance and screening and testing, there is an important concept called moral‬
‭hazard‬
‭1.‬ ‭Moral hazard is the counterargument to "the right to know" and "the right not know"‬
‭●‬ ‭Insulating people from risk may make them less concerned with the potential negative‬
‭consequences of that risk than they otherwise might be‬
‭1.‬ ‭Preventing people from understanding their risks might make them less concerned with‬
‭potential negative consequences‬
‭2.‬ ‭Ex: know that smoking causes cancer and if we don't tell this to people, they are going to‬
‭become less concerned with the potential negative consequences‬
‭■‬ ‭In turn, has implications for HC system and the COST‬
‭●‬ ‭Health insurance in US (or Canadian private health insurance) always incorporates moral hazard‬
‭into its policy application‬
‭●‬ ‭Co-pay or deductible or refusal to provide policies for high risk‬
 ‭1.‬ C ‭ o-pay gives you a small portion of the overall cost -- makes you more in tune with the‬
‭overall value of what you are getting‬
‭2.‬ ‭Deductible‬
‭■‬ ‭Ex: seniors have to pay the first "X" amount of dollars then the rest of their drugs‬
‭are covered‬
‭3.‬ ‭This puts some of the responsibility of the negative consequences on the individual (e.g.‬
‭misuse of emergency departments, engaging in risky health behaviours, etc.)‬
‭ ‬ ‭Often a policy decision to work on moral hazard for either:‬
●
‭1.‬ ‭The benefit of reducing overall costs to provide for that aspect of society‬
‭2.‬ ‭Or to make people more aware/more careful‬

‭●‬ ‭Ex: Florida housing insurance problem‬

‭○‬ ‭Stories of families unable to rebuild homes due to moral hazard‬
‭○‬ ‭Gonna keep getting hit by hurricanes and not gonna keep rebuilding‬
‭○‬ ‭Insurance companies decided that they are no longer going to provide policies for high‬
‭risk‬
‭●‬ ‭People who have genetic conditions that are identified through screening and testing are similar to‬
‭a hurricane‬
‭○‬ ‭Have potential for damage‬
‭○‬ ‭Going to get more costly overtime‬
‭○‬ ‭If an insurer knows that there is a preexisting risk, they may not insure that person at all‬
‭○‬ ‭This happens a lot in the US‬
‭○‬ ‭This happens with pets in Canada's as well‬

‭Prospect Theory‬
‭●‬ ‭Recall: connects to the psychological impact of harm that may result from testing‬
‭○‬ ‭Prospect theory is a way for us to look at that idea‬
‭●‬ ‭Prospect theory‬‭: people tend to react differently to gains than to losses (risk averse to losses but‬
‭less so for gain – e.g. lottery tickets)‬
‭○‬ ‭Ex: They don't want to lose money but happy to buy lottery tickets‬
‭●‬ ‭people make decisions on the basis of subjective assessments of probabilities which may be quite‬
‭different from the objective or true probabilities.‬
‭○‬ ‭The right to know, the right to remain ignorant, and the critical arguments of moral‬
‭hazard all go into prospect theory because people in the HC system make decisions on if‬
‭they want to know or not know, based on subjective assessment of probabilities‬
 ‭ ‬ ‭Which may or may not be different from reality‬
○
‭ ‬ ‭i.e. like framing can alter risk perception (Deber and Mah, 2014)‬
●
‭○‬ ‭Framing, how people have different decision theories and scaffolds, and worldviews are‬
‭going to assess risk DIFFERENTLY and usually assess risk based on PROBABILITIES‬
‭○‬ ‭Ex: If statistics say you have "X" percentage likelihood of developing skin cancer if‬
‭you've been burnt severely by the sun 2 times‬
‭■‬ ‭People tend to make decisions based on those probabilities‬
‭■‬ ‭Which may or may not be true‬

‭●‬ ‭Chart:‬
‭○‬ ‭People make SUBJECTIVE assessments of probabilities‬
‭■‬ ‭Internal assessment‬
‭■‬ ‭People tend to UNDERESTIMATE their likelihood of heart disease, cancer,‬
‭and other natural causes by a significant amount‬
‭■‬ ‭People tend to OVERESTIMATE their likelihood of being involved in an‬
‭accident, homicide, or other unnatural cause‬
‭○‬ ‭Reality vs Subjective‬
‭■‬ ‭Ex: Someone who smokes a pack of cigs a day may not see themselves as high‬
‭risk for lung cancer. But statistical estimate may be HIGHER‬
‭●‬ ‭Just based on worldview and framing mechanisms, you are going to see risks differently‬
‭○‬ ‭And most of society does not have access to or care to find statistical estimates that they‬
‭face daily‬
‭○‬ ‭Part of their decision theory is related to prospect theory in that they have created‬
‭scaffolds or structures as to how they perceive risks and this helps guide them without‬
‭them thinking about it, in terms of making decisions relative to the right to know or the‬
‭right to remain ignorant‬
‭Discrimination and Confidentiality‬
‭●‬ ‭Confidentiality means your data is identifiable but it is kept safe and it is ONLY used by the‬
‭people who need to use it‬
‭●‬ ‭Discrimination can take place if confidential information gets out and is used against you‬
‭●‬ ‭People are treated differently by their employer or insurance company because they have a gene‬
‭or mutation that increases risk of inherited disorder‬
‭○‬ ‭In the US especially‬
‭○‬ ‭Some of them are external to the place that they work, others not‬
‭●‬ ‭USA - GINA; Canada - GNDA‬
‭○‬ ‭To counteract these problems, a policy response to the proliferation of genetic‬
‭information and the right to know and not knowing, and more people knowing exist‬
‭○‬ ‭These are two pieces of federal legislation that prevent discrimination on the basis of‬
‭genetic information‬
‭●‬ ‭USA --‬‭Genetic Information Non-Disclosure Act (GINA)‬
‭○‬ ‭GINA prevents insurers from using genetic information to‬
‭■‬ ‭Determine whether someone is eligible for insurance‬
‭■‬ ‭Can't use that info for underwriting (i.e. determining risk which creates the cost‬
‭you pay for insurance)‬
‭●‬ ‭Canada --‬‭Genetic Non-Disclosure Act (GNDA)‬
‭○‬ ‭GNDA in Canada‬
‭○‬ ‭Essentially the same as GINA‬
‭○‬ ‭Protects Canadians from discrimination based on genetic characteristics‬
‭○‬ ‭Genetic info can't be demanded from you, nor can they be used against you‬
‭○‬ ‭GNDA recently survived a constitutional challenge in 2020 (deemed constitutional)‬
‭○‬ ‭In relation to the GNDA, appropriate amendments to the Labour Code and‬‭Canadian‬
‭Human Rights Act‬
‭■‬ ‭So that all of the policy instruments (in this case legislation or regulatory) are‬
‭ALIGNED‬
‭■‬ ‭Important to align legislation across ALL SPHERES so that it's consistent‬
‭○‬ ‭Labour Code amendments‬
‭■‬ ‭Employers cannot demand genetic info, nor can they use it to discriminate‬
‭against staff‬
‭○‬ ‭Canadian Human Rights Act‬
‭■‬ ‭Then it becomes written into the Human Rights Act‬
‭■‬ ‭As well as the Ontario Human Rights Legislation to be consistent‬
‭○‬ ‭There is often a delay‬
‭■‬ ‭Gives governments time to impose changes to their legislation to follow the suit‬
‭with the federal level‬
‭○‬ ‭GNDA does not apply to family history, diagnosis of manifested disease or symptoms‬
‭■‬ ‭Law doesn't apply to genetic testing related to manifested disease‬
‭■‬ ‭Or family history‬
‭●‬ ‭GINA prevents health insurers from using genetic information to determine if someone is eligible‬
‭for insurance or to make coverage, underwriting, or premium decisions‬
 ‭●‬ G ‭ NDA protects Canadians from discrimination based on genetic characteristics – can’t be‬
‭demanded or used against someone‬
‭●‬ ‭GNDA survived a constitutional challenge in 2020; amendments to Labour Code and Canadian‬
‭Human Rights Act‬
‭●‬ ‭GNDA doesn’t apply to family history, diagnosis of manifested disease or symptoms‬

‭Direct to Consumer Genetic Testing‬

‭●‬ ‭Important to understand privacy risks, especially if your data is combined with other information‬
‭○‬ ‭Balance the risks and benefits of that‬
‭○‬ ‭Sent in genetic sample for a specific purpose, but should be careful to specific whether‬
‭you agree that it can be stored later or stored anonymously‬
‭○‬ ‭Privacy risk‬
‭●‬ ‭GNDA prohibits organizations to collect, use, or disclose genetic test results without consent‬
‭○‬ ‭If you visit Ancestry.ca, it is expected that this info stay confidential‬
‭●‬ ‭Importance of transparency among providers‬
‭○‬ ‭People who participate in genetic testing make sure they explain the risks to patients‬
‭when this type of work is conduced‬
‭○‬ ‭Consent is important‬
‭○‬ ‭Where to info is being collected, where it is stored, how it will be used, how long it will‬
‭be stored‬
‭●‬ ‭Research is a separate consent‬

‭Hidden effects of Mendelian inheritance‬

‭●‬ ‭There are so many individuals with undiagnosed disease and we don't appreciate how many there‬
‭are‬
‭●‬ ‭Emphasizes the importance of genetic analysis in helping clinicians understand when someone‬
‭presents‬

‭Screening Newborns‬
‭●‬ ‭Congenital Hypothyroidism‬
‭○‬ ‭Pros: Highly sensitive, acceptable specificity, inexpensive, non-invasive small blood‬
‭sample‬
‭○‬ ‭Cons: Not preventative (but can administer treatment after testing)‬
‭●‬ ‭Sickle Cell Anemia‬
‭○‬ ‭Pros: More prevalent in certain ethnicities, inexpensive treatment‬
‭○‬ ‭Cons: Not all treatment is effective, not prevalent in Canada, less successful prophylaxis‬
‭●‬ ‭Krabbe Disease‬
‭○‬ ‭Pros: Life-threatening disease, severe disease complications‬
‭○‬ ‭Cons: Not very prevalent (1/100,000), Expensive treatment and may be without benefit,‬
‭potential for over diagnosis‬
‭●‬ ‭Duchenne Muscular Dystrophy (DMD)‬
‭○‬ ‭Pros: Selective disease, Highly Specific, Carrier Testing (mothers), highly sensitive‬
‭○‬ ‭Cons: Expensive, Invasive,No treatment, Pregnancy termination issues‬
‭●‬ ‭Cystic Fibrosis‬
 ‭ ‬ ‭Pros: Carrier, non-invasive test, prevents long term health issues, specific‬
○
‭○‬ ‭Cons: Not highly sensitive (false positives common), pregnancy termination‬
‭●‬ ‭Deber & Mah, 2014‬
‭○‬ ‭There were only 5 things that they screened for in newborns in 2014 compared to now‬
‭where they screen for MANY more‬
‭○‬ ‭In 10 years, the ability of tests to be specific and sensitive, and predictive value has‬
‭improved and has changed how screening is done‬
‭ ‬ ‭Policy in this area is not static‬
●
‭○‬ ‭Screening is appropriate when testing continues (this is an example of that)‬
‭○‬ ‭Screening expanded a lot over the last 10 years‬

‭Other Screening Programs - Ontario‬

‭●‬ ‭4 Cancer Screening Programs in Ontario‬
‭○‬ ‭Colon Cancer Check: Fecal Occult Blood Test‬
‭○‬ ‭Ontario Breast Screening Program‬
‭○‬ ‭Ontario Cervical Screening Program‬
‭○‬ ‭Ontario Lung Screening Program‬
‭●‬ ‭All these programs have been found to be effective from cost effectiveness analysis‬
‭○‬ ‭The money spend on screening promotion is FAR LESS than if they let those diseases run‬
‭their course and have to later treat them in the HC system‬
‭○‬ ‭Economically feasible and better in the long run to spend money on screening than spend‬
‭way more money on treatment‬
 ‭●‬ ‭Data breech of confidential information and now going bankrupt‬

‭Contemporary Applications of Genetic Medicine‬

‭●‬ ‭Dr. Kim’s Lab – Personalized Medicine @ UH‬
‭○‬ ‭https://www.schulich.uwo.ca/clinpharm/education/clinical_programs/p‬
‭ersonalized_medicine.html‬
‭○‬ ‭Assesses patients genetically‬
‭○‬ ‭Understanding the basis of your genetics and use of pharmacological‬
‭●‬ ‭Centre for Precision Medicine @ Vanderbilt‬
‭○‬ ‭https://www.vumc.org/cpm/‬
‭●‬ ‭LHSC Medical Genetics Department @VH‬
 ‭○‬ h ‭ ttps://www.lhsc.on.ca/medical-genetics-program-of-southwesternontario/medical-geneti‬
‭cs-program-of-southwestern-ontario-2‬
‭○‬ ‭Prenatal, cancer, newborns, mitochondrial screening‬
‭○‬ ‭Medical geneticists to council people if its actionable or not‬
‭ ‬ ‭Cancer Care Ontario -- Screening‬
●
‭○‬ ‭A lot more emphasis on in bringing in the best science into health care practice in both‬
‭screening programs and surgery‬

‭To Screen or Not Screen, That is the Question…‬

‭●‬ ‭“…Whether 'tis nobler in the mind to suffer the slings and arrows of outrageous fortune, or to‬
‭take arms against a sea of troubles and by opposing end them.”‬
‭○‬ ‭(Hamlet, in Hamlet – Shakespeare, 1609)‬
‭●‬ ‭Importance of autonomy, privacy, and risk‬
‭○‬ ‭Diff people = diff worldviews = some people want to know and others don't‬
‭○‬ ‭Some policy in terms of right to know are non-negotiable -- if you have discovered abuse‬
‭of a child or if someone is going to harm themselves then the law requires you to report,‬
‭but there is no such thing for genetic information‬
‭○‬ ‭Person has right to make their own decision‬
‭○‬ ‭When they make a decision their data should be kept safe and private‬
‭●‬ ‭Cost-benefit‬
‭○‬ ‭Governments do cost-benefits of these programs‬
‭○‬ ‭Cost-effectiveness analysis is a way that data from health care is analyzed to determine if‬
‭the cost of a screening program is actually beneficial‬
‭○‬ ‭Is it going to cost us less in the long run to screen and identify early rather than let it run‬
‭its course?‬
‭●‬ ‭Cultural, situational, and structural contexts‬
‭○‬ ‭Diff people see things diff, background and worldviews are diff‬
‭○‬ ‭Working the balance between doing what you think is right in health care and what‬
‭people believe‬