我們要如何正視 消費者基因檢測? ( ) 王子豪 台灣精準醫學學會秘書長長庚大學教授林口長庚醫院主治醫師. Tzu-Hao Wang, MD., PhD.

Transcription

1 我們要如何正視 消費者基因檢測? ( ) 王子豪 台灣精準醫學學會秘書長長庚大學教授林口長庚醫院主治醫師 1

2 The U.S. Food and Drug Administration today allowed marketing of 23andMe Personal Genome Service Genetic Health Risk (GHR) tests for 10 diseases or conditions (see the next slide) These are the first direct-to-consumer (DTC) GHR tests authorized by the FDA. The FDA granted market authorization of the Personal Genome Service GHR tests to 23andMe, Inc. 2

3 Genetic Health Risk (GHR) tests for 10 diseases or conditions Parkinson s disease, a nervous system disorder impacting movement; Late-onset Alzheimer s disease, a progressive brain disorder that destroys memory and thinking skills; Celiac disease, a disorder resulting in the inability to digest gluten; Alpha-1 antitrypsin deficiency, a disorder that raises the risk of lung and liver disease; Early-onset primary dystonia, a movement disorder involving involuntary muscle contractions and other uncontrolled movements; Factor XI deficiency, a blood clotting disorder; Gaucher disease type 1, an organ and tissue disorder; Glucose-6-Phosphate Dehydrogenase deficiency, also known as G6PD, a red blood cell condition; Hereditary hemochromatosis, an iron overload disorder; and Hereditary thrombophilia, a blood clot disorder. In addition, the FDA intends to exempt additional 23andMe GHR tests from the FDA s premarket review, and GHR tests from other makers may be exempt after submitting their first premarket notification. A proposed exemption of this kind would allow other, similar tests to enter the market as quickly as possible and in the least burdensome way, after a one-time FDA review. 3

4 It is the first direct-to-consumer (DTC) test to report on three specific BRCA1/BRCA2 breast cancer gene mutations that are most common in people of Ashkenazi (Eastern European) Jewish descent. These three mutations, however, are not the most common BRCA1/BRCA2 mutations in the general population. The FDA granted the marketing authorization to 23andMe. 4

5 MIT Technology Reviews 5

6 Outlines I. Laboratory Biotech. Industry Healthy individuals Consumers Physicians/Counselors Healthcare providers Regulatory agents Government 6

7 DTC testing is essentially a commercialization of technologies being marketed to the general masses. FOR PROFIT. - Clinical Chemistry (2017) 63: 635 David Grenache Professor Dept. of Pathol. Univ. of Utah Michael Joyner Professor Anesthesiology Mayo Clinic, MN Daniel Holmes Division head Clinical Chemistry St. Paul s Hosp. Vancouver Rodger Seccombe CEO HealthTab Inc, Vancouver Why 7

8 a Trojan horse effort to get health information and DNA from a large sample in an effort to generate big data and look for rare variants that might give insight into potentially druggable or therapeutic targets. -Michael J. Joyner Why 8

9 How 9

10 Get results in 6-8 weeks. How 10

11 Color Genomics How 11

12 Direct-to-consumers For healthcare providers How 12

13 How 13

14 Slogan: The science of you. Take control of your health. Direct to consumers: all kinds of lab tests! How 14

15 消費者基因檢測能夠扮演什麼醫療角色嗎? Conclusion: 23andMe reports provide some useful pharmacogenetics information, mirroring clinical tests that are in standard use. Other tests are unspecific, providing limited guidance and may not be useful for patients without professional interpretation. Nevertheless, DTC companies like 23andMe act as a powerful intermediate step to integrate pharmacogenetic testing into clinical practice. How 15

16 現在的消費者基因檢測存著什麼問題呢? Results: Our analyses indicated that 40% of variants in a variety of genes reported in DTC raw data were false positives. In addition, some variants designated with the increased risk classification in DTC raw data or by a third-party interpretation service were classified as benign at Ambry Genetics as well as several other clinical laboratories, and are noted to be common variants in publicly available population frequency databases. How 16

17 Analytic validity ( 分析確效性 ) Clinical validity ( 臨床確效性 ) Clinical utility ( 臨床實用性 ) What 17

18 Slide by Muin J Khoury, 2018 Precision Medicine symposium, held in University of Utah Dotson WD et al. Clinical Pharmacology &Therapeutics (2014) 95: What 18

19 What ACMG, American College of Medical Genetics and Genomics; ACOG, American Congress of Obstetricians and Gynecologists; AHRQ EPC, Agency for Healthcare Research and Quality Evidence-based Practice Center; ASCO, American Society of Clinical Oncology; BCBSA TEC, Blue Cross Blue Shield Association Technology Evaluation Center; CMS, Centers for Medicare & Medicaid Services; CPG, clinical practice guideline; CPIC, Clinical Pharmacogenetics Implementation Consortium; EGAPP, Evaluation of Genomic Applications in Practice and Prevention; NCCN, National Comprehensive Cancer Network; NICE, National Institute for Health and Clinical Excellence; PWG, Pharmacogenetics Working Group; SR, systematic review; USPSTF, US Preventive Services Task Force. Dotson WD et al. Clinical Pharmacology &Therapeutics (2014) 95:

20 對基因檢測公司 ( 生技產業 ) 的建議 : 1. 從大眾消費產品提升到醫療輔助工具 ( 不只是用削價來佔有市場 ) 2. 和醫學界加強互動 充分溝通 基因變異性的解讀要改善 檢測前 / 後的遺傳諮詢 建立可讓醫生處方的附加確證檢驗 (additional validating tests) What 20

21 Outlines Laboratory Biotech. Industry II. Healthy individuals Consumers Physicians/Counselors Healthcare providers Regulatory agents Government 21

22 The right to know. 23andMe promotes the tests as intended to inform users of lifestyle choices and/or encourage conversations with a healthcare professional. Premise ( 雖然這個大前提並不一定適用每個人 ): The consumer will make rational decision based on available information. 數據資訊知識 Why 22

23 Appealing Characteristics of DTC genetic tests: Affordable price ( 親民的價格 ) Price transparency ( 消費者可網上比價, 自己斟酌願意付多少錢 ) Friendly App for presenting data ( 讓消費者自以為看懂了 ) Empowered individuals for pro-health ( 有掌握自己的健康資訊的感覺 ) 強化了消費者的自主權! Why 23

24 哪些人會選擇做消費者基因檢測? Of 13,749 respondents, 16.7% resided in rural areas, 13.8% were Hispanic, and 10.1% were non-hispanic black. Rural residents were less likely than urban residents to report awareness of genetic testing (OR = 0.74, 95% CI = ). Compared with non-hispanic whites, racial/ethnic minorities were less likely to be aware of genetic testing: Hispanic (OR = 0.68, 95% CI = ); and non-hispanic black (OR = 0.74, 95% CI = ). Why 24

25 消費者基因檢測資料會改善保健行為嗎? Longitudinal data were available for 1,002 participants. Significant increases were observed for vegetable intake (mean Δ = 0.11 (95% CI = 0.05, 0.17), p = ) and strength exercise (Δ = 0.14 (0.03, 0.25), p=.0153). Genetic results were not consistently associated with any diet or exercise changes. How 有想到要做 DTC-GT, 就是有意願想促進健康 25

26 消費者基因檢測會造成民眾的負面影響嗎? Conclusions: The impact of DTC-GT on consumers health perceptions and behaviors is an emerging concern. However, negative effects on consumers or health benefits have yet to be observed. Nevertheless, since the online market of DTC-GT is expected to grow, it is important to remain aware of a possible impact. How 26

27 做了消費者基因檢測, 能進一步利用資料嗎? How 27

28 民眾要如何選擇消費者基因檢測? 要先看清楚網頁上或文件上細字條文 消費者要如何看懂這些基因檢測資料? 1. 先要有基礎生物學知識 ( 染色體 DNA 基因 ) 2. 最好有基礎統計學常識和基礎的機率觀念 ( 如果大部分民眾有這些基本知識, 就不會隨著媒體窮緊張 ) What 28

29 Outlines Laboratory Biotech. Industry III. Healthy individuals Consumers Physicians/Counselors Healthcare providers Regulatory agents Government 29

30 2016 By Wylie Burke, MD., PhD. Annals of Internal Medicine (2016) 164: Arguably, professional societies should not need to take on this educational task, and physicians should not spend valuable time in the clinical encounter deflating a misguided marketing message. However, DTC genetic testing is not the first (or the last) health product to generate unrealistic hopes Annals of Internal Medicine (2017) 167: We share the FDA and 23andMe's belief that genetic information is valuable and may affect health maintenance. However, we believe that the currently approved 23andMe test is extremely limited in its clinical utility and fear that it opens the door for a new pathway for fast-track approval of genetic testing with minimal oversight. Why 30

31 這陣陣 DTC-GT 的潮流誰也擋不住, 醫界不得不面對!( 最好能利用它 ) Adrian Burton. Lancet Neurology (2015) 14: We cannot un-invent this technology, which may indeed turn out to be a powerful way of helping individuals manage their health better and save health systems billions. Why 31

32 (2016)164: 多少比例的消費者會拿著她 / 他的 DTC-GT 資料, 去請教醫師? 27% 8% 65% Why 32

33 ACMG's first Statement on Direct to Consumer Genetic Testing was published in 2004, followed by statements in 2008 and 2015, as the field has evolved. more than 1,000 BRCA1 and BRCA2 mutations known to correspond to increased cancer risk, It is important to note that this test does not provide information on which a person should make medical decisions. Even in someone who is Ashkenazi Jewish, a negative result that leads to false reassurance of risk could reduce the chances that an individual pursues the best tests and health practices in the future (including for example, mammograms) for their own risk indicators. How 33

34 the three mutations reported by 23andMe's test show up in 2.5 percent of Ashkenazi Jewish people but only up to 0.1 percent of individuals from other ethnic groups. "I don't want to see any more women die of ovarian and breast cancer. My motive is very simple," Mary-Claire King said. 23andMe's DTC test for select BRCA variants "will increase the likelihood of that happening and not decrease it." How 34

35 分析各家消費者基因檢測公司配套的遺傳諮詢 Middleton A et al. Personalized Medicine (2017) 14(3): We argue that direct-to-consumer genetic testing companies should make genetic counseling available, pre-test as well as post-test. if the testing process has the potential to cause psychological distress, then companies have a responsibility to provide support and should not rely on traditional healthcare systems to pick up the pieces. How 35

36 How Middleton A et al. Personalized Medicine (2017) 14(3):

37 學會網頁 ( 新知分享專欄 最重要的是要能深入的提供 : 檢測前教育和諮詢 (pre-test education and counseling) 知情同意書 (informed consent) 和檢測後諮詢 (post-test counseling) 都必須分別填妥知情同意書, 因為檢測的結果可能會揭露偶發的發現 (incidental findings) 或二級發現 (secondary findings), 例如 : 癌症相關的基因突變 精神疾病相關突變 成年之後才可能發病的疾病基因等等 遺傳諮詢太重要了! What 37

38 學會網頁 新知分享專欄 SLC9A9 基因變異曾經被發現於自閉症 注意力缺陷過動症 (ADHD) 和癲癇 What 38

39 Outlines Laboratory Biotech. Industry Healthy individuals Consumers Physicians/Counselors Healthcare providers IV. Regulatory agents Government 39

40 1. The FDA s pre-certification pilot program (FDA Pre-Cert): DCT- GT, digital health technology, and cell-based regenerative medicine, 2. De novo reviewing classification for some tests that fulfill requirements for assuring the tests accuracy, reliability and clinical relevance, and 3. To exempt certain tests from premarket review: genetic carrier screening tests. Why 40

41 Dual regulatory pathways for genetic tests in the US: 1. Through CLIA (clinical laboratory improvement amendments) certified laboratory, and 2. Via the FDA for companies that volunteer to submit to FDA or are required to after receiving a warning letter. Three federal agencies are responsible for CLIA: The Food and Drug Administration (FDA), Center for Medicaid Services (CMS), and the Center for Disease Control (CDC). Each agency has a unique role in assuring quality laboratory testing. Why 41

42 1. Providing an overview of laws that could potentially impact the regulation of DTC genetic testing in 26 European countries, 2. Essentially ban DTC-GT (France and Germany) vs. nearly no regulation (Luxembourg and Poland), countries requiring Medical Supervision (Austria, France, Germany, Hungary, Italy, Lithuania, The Netherlands, Slovenia, Portugal, Spain), countries requiring Genetic Counseling, countries requiring Written Informed Consent specifically for genetic testing. How 42

43 How 43

44 1. 政府監督管理 DTC-GT, 最終的目標在於保障民眾健康, 而 DTC-GT 的精神也是促進民眾自主健康管理, 2. 連美國有嚴格把關傳統的 FDA, 都能在審核機制彈性鬆綁, 幫助產業界能迅速 有效地將安全而創新的基因檢測推廣給消費者, 3. 台灣也能借鏡這種精神來管理 : 一方面鼓勵產業發展, 一方面又不流失安全, 4. 台灣的人口不多 種族的均質性高 又有健保為最大的醫療給付者, 有推動精準醫療的絕對優勢, 建議趁早打造精準醫療的基礎建設 - 全民電子健康資訊系統, 將消費者基因檢測獲得的資料, 也能納入個人的健康紀錄 What 44

45 學會網頁 ( 新知分享專欄 FHIR (Fast Healthcare Interoperability Resources) 是一種衆所期待, 且已在美國逐漸被接受的數據標準 (data standard) 用來描述電子病歷 (Electronic Health Record, EHR) 的數據格式 (data format) 和數據元 (data elements) 提供標準系統化資訊於應用程式介面 (Application Programming Interface, API) What 45

46 學會網頁 新知分享專欄 What 46

47 Take-home messages (1) Paradigm shift should be realized by physicians: Good patient care is ongoing relationship-based patient care. Mind-set: Paternalism Expert advisor Role: Gate keepers Partners Adapted from: Clinical Chemistry (2017) 63:

48 Take-home messages (2) Laboratory Biotech. Industry CME (updating Dr s genomic medicine) App. for clinic and consumers. Healthy individuals Consumers Physicians/Counselors Healthcare providers Basic statistics Probability knowledge Regulatory agents Government Providing appropriate Infrastructure of EHR (e.g., FHIR) 48

49 謝謝聆聽 敬請指正 王子豪 49