Medical Utopias

Medical UtopiasEthical Reflections about Emerging Medical TechnologiesDr Alex Tang MD PhDConsultant PaediatricianKPJ Johor Specialist Hospital

1Living without pain, diseases or even dyingNo more fertility or reproductive problemsDelaying or defying the aging processPersonalized genomic medicine (P4 Medicine)personalised, predictive, preventive, participatoryOptimize and enhance normal abilities

Medical Utopiaspersonalized, predictive, preventive, and participatory. Some call personalized genomic medicine2Medical Utopias and Emerging Technologies3Biomedical Ethics FrameworkBeauchamp and Childress; Principles Biomedical Ethics, OUP, 5th edition 2001The Four Principles are general guides that leave considerable room for judgement in specific cases.Respect for autonomy: respecting the decision-making capacities of autonomous persons; enabling individuals to make reasoned informed choices.Beneficence: this considers the balancing of benefits of treatment against the risks and costs; the healthcare professional should act in a way that benefits the patientNon maleficence: avoiding the causation of harm; the healthcare professional should not harm the patient. All treatment involves some harm, even if minimal, but the harm should not be disproportionate to the benefits of treatment.Justice: distributing benefits, risks and costs fairly; the notion that patients in similar positions should be treated in a similar manner.

4Already in clinical applications (include phase 3 trials)Research fields at preclinical stagesResearch fields at purely theological stages

Ethical areas of concern5Already in clinical applications (include phase 3 trials) tissue engineering, bioelectronics, health IT, genetic tests, drugs testingResearch fields at preclinical stages -reproductive cloning, germ line genome modification, interventions in biological aging processResearch fields at purely theological stages nanotechnology, virtual digital patient

Ethical areas of concern6The emergence of the digital patient (to be or not be be)The direct to customer (DTG) genetic screening (to know or not to know)The development of new pharmaco-therapeutics (to treat or not to treat)

Ethical Reflections on Emerging Medical Technologies

7Medical UtopiasEthical Reflections about Emerging Medical Technologies1. The Emergence of the Digital Patient8Ethical Reflection on the Digital Patient9Use and Characteristics of Electronic Health Record Systems Among Office-based Physician Practices: United States, 20012013

NCHS Data Brief Number 143, January 2014http://www.cdc.gov/nchs/data/databriefs/db143.htmPercentage of office-based physicians with EHR systems: United States, 20012013HITECHMedicare and Medicaid EHR Incentive ProgramsChun-Ju Hsiao, Ph.D., and Esther Hing, M.P.H.Key findingsIn 2013, 78% of office-based physicians used any type of electronic health record (EHR) system, up from 18% in 2001.In 2013, 48% of office-based physicians reported having a system that met the criteria for a basic system, up from 11% in 2006. The percentage of physicians with basic systems by state ranged from 21% in New Jersey to 83% in North Dakota.In 2013, 69% of office-based physicians reported that they intended to participate (i.e., they planned to apply or already had applied) in "meaningful use" incentives. About 13% of all office-based physicians reported that they both intended to participate in meaningful use incentives and had EHR systems with the capabilities to support 14 of the Stage 2 Core Set objectives for meaningful use.From 2010 (the earliest year that trend data are available) to 2013, physician adoption of EHRs able to support various Stage 2 meaningful use objectives increased significantly.The Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009 authorized incentive payments to increase physician adoption of electronic health record (EHR) systems (1,2). The Medicare and Medicaid EHR Incentive Programs are staged in three steps, with increasing requirements for participation. To receive an EHR incentive payment, physicians must show that they are "meaningfully using" certified EHRs by meeting certain objectives (3,4). This report describes trends in the adoption of EHR systems from 2001 through 2013, as well as physicians' intent to participate in the EHR Incentive Programs and their readiness to meet 14 of the Stage 2 Core Set objectives for meaningful use in 2013.

10Ethical Reflections: Digital PatientFDASIA Health IT Report April 2014Health management health IT functionalities (sometimes referred to as clinical software) include, but are not limited to:Health information and data management; Data capture and encounter documentation;Electronic access to clinical results;Most clinical decision support;Medication management (electronic medication administration records);Electronic communication and coordination (e.g. provider to patient, patient to provider, provider to provider, etc.);Provider order entry;Knowledge (clinical evidence) management;Patient identification and matching.Health IT with medical device functionality. Examples include computer aided detection/diagnostic software computer aided detection software and remote display or notification of real-time alarms from bedside monitors, radiation treatment planning, and robotic surgical planning and control software. This is considered high risk to patients.

11Is health IT the key to better healthcare?Ethical reflection

12One quarter of the hospitalizations (937 admissions) had at least 1 ADE9% resulted in serious harm, 22% in additional monitoring and interventions, 32% in interventions alone, and 11% in monitoring aloneErrors associated with ADEs: 61% ordering, 25% monitoring, 13% administration, 1% dispensing, and 0% transcriptionNebeker JR, Hoffman JM, Weir CR, Bennett CL, Hurdle JF. High Rates of Adverse Drug Events in a Highly Computerized Hospital. Arch Intern Med. 2005;165(10):1111-1116. doi:10.1001/archinte.165.10.1111. Adverse Drug Events (ADEs) in a Highly Computerized Hospital (20 week period)After implementation of electronic resources at a Veterans Administration hospital (eg, electronic medical records [EMRs], computerized provider order entry [CPOE], integrated checking of allergies and drug-drug interactions, and bar coding), pharmacists identified and categorized nearly 500 ADEs over a five-month period. Results suggested that 25% of hospitalizations were associated with at least one ADE, accounting for an event rate of 52 ADEs per 100 admissions. The majority of errors that resulted in an ADE occurred in the medication ordering phase. The authors conclude that whilethere isacapacity to safely administer drugs using computers,more appropriate decision support at high-risk stepswould improve current systems.

Methods Using explicit standardized criteria, pharmacists classified inpatient ADEs from prospective daily reviews of electronic medical records from a random sample of all admissions during a 20-week period at a Veterans Administration hospital. We analyzed ADEs that necessitated a changed treatment plan.Results Among 937 hospital admissions, 483 clinically significant inpatient ADEs were identified, accounting for 52 ADEs per 100 admissions and an incidence density of 70 ADEs per 1000 patient-days. One quarter of the hospitalizations had at least 1 ADE. Of all ADEs, 9% resulted in serious harm, 22% in additional monitoring and interventions, 32% in interventions alone, and 11% in monitoring alone; 27% should have resulted in additional interventions or monitoring. Medication errors contributed to 27% of these ADEs. Errors associated with ADEs occurred in the following stages: 61% ordering, 25% monitoring, 13% administration, 1% dispensing, and 0% transcription. The medical record reflected recognition of 76% of the ADEs.Conclusions High rates of ADEs may continue to occur after implementation of CPOE and related computerized medication systems that lack decision support for drug selection, dosing, and monitoring.

13Health IT Sociotechnical SystemFDASIA Health IT Report April 2014The components of a health IT sociotechnical system include: the technology (e.g. the hardware and software of health IT), the people (e.g. individuals working within the system including healthcare providers and implementers of health IT), the processes (e.g. the workflow of healthcare delivery), the organizations (e.g. how an organization installs and configures health IT)the external environment (e.g. the environment in which the organizations operate).

14Poorly designed health IT new hazards in an already complex system of health care deliveryIndividual health IT components may meet their stated performance requirements, yet the system as a whole may yield unsafe outcomesProblematic events involving complex systems often cannot be ascribed to a single causative factorPoor human-computer interactions can contribute to serious injury and death

Issues in health IT Sociotechnical System15e-iatrogenesise-iatrogenicIssues in health IT Sociotechnical SystemTechnologically induced errors are significant and increasingly more evident in care delivery systems. Terms to describe this new area of error production include the label technologicaliatrogenesis[33]for the process and e-iatrogenic[34]for the individual error. The sources for these errors include:Prescriber and staff inexperience may lead to a false sense of security; that when technology suggests a course of action, errors are avoided.Shortcut or default selections can override non-standard medication regimens for elderly or underweight patients, resulting in toxic doses.CPOE and automated drug dispensing was identified as a cause of error by 84% of over 500 health care facilities participating in a surveillance system by theUnited States Pharmacopoeia.[35]Irrelevant or frequent warnings can interrupt work flow.Healthcare information technology can also result in iatrogenesis if design and engineering are substandard, as illustrated in a 14-part detailed analysis done at the University of Sydney

16Is health IT the key to better healthcare?Data interoperability will it ever be resolved? Ethical reflection

17Health IT is a practical tool not a replacement for quality patient care Ethical reflection

Norman Rockwell, Saturday Post Archives18Ethical Reflection on the Digital Patient19Ethical reflection

20Most patients not aware of their right to privacy and confidentialityCheaper and faster to develop non-privacy aware health IT software solutionsHealthcare provider consolidationHackersPrivacy, confidentiality, security: how safe is the data?

EmployersInsurance companiesLawThere has been considerable discussion about the effects of consolidation on health care cost and quality, but there has been virtually no discussion about the significant effects of consolidation on health privacy.A brief example involving a hospital purchasing a physician practice will illustrate how health care consolidation threatens health privacy. Assume that you received mental health treatment from a psychiatrist in private practice, and your mental health records were stored at your psychiatrists office and not disclosed without your authorization. Further assume that a local hospital subsequently purchased your psychiatrists practice. When you later visit the hospitals emergency department for treatment of a sprained ankle sustained in the company softball game, the physicians and nurses access your integrated electronic health record (EHR), including records from all of the hospital-owned practices. As a result, your mental health records, which you assumed were confidential, are now accessible by the physicians and nurses treating your ankle.

21Is our healthcare providers keeping their data secure?Are we educating our patients on their privacy rights?Do we allow patient to access their own medical records?Data Protection RegulationEthical reflection

22Medical UtopiasEthical Reflections about Emerging Medical Technologies2. Direct to Customers (DTC) genetic screeningThe human genome consists of 3 billion base pairs. Coding part of the DNA is called exome. The genome may be sequenced (without bioinformatics analysis) by a private company for USD$6995 (data for autumn 2012) while an exome for USD$895. Exome examine is routine for diagnosis of some neurological diseases. This proves more data that was asked for. Hence the need for Report of IBC on the Principle of Non-Discrimination and Non-Stigmatization (2014).23

Direct To Consumer (DTC) Screening Tests

Direct to Consumers Tests (DTC tests)Consumer companies are providing services for people who wants to know and are willing to pay. According to a list compiled by the Genetics and Public Policy Centre (USA), there were at least 29 companies, most of which have headquarters in the USA, selling direct-to-consumer (DTC) genetic tests in May 2010 (Genetics and Public Policy Center 2011). The types of tests sold by these companies include single gene tests, multiple genes tests and genome-wide-testing also known as personal genome scanning, whereby hundreds of thousands to millions of genetic markers (often single nucleotide polymorphisms) are tested throughout the genome. Although the majority of the popular media coverage and much of the academic debates have focussed on companies selling genome-wide-testing services (i.e. from companies such as 23andMe, deCODE and Navigenics), most DTC genetic testing companies, in fact, do not sell this type of testing. Also contributing to the variation in the DTC genetic testing market is the great deal of variation regarding the purpose of the tests on offer; for example, different tests can provide information regarding ancestry, carrier status, disease risk (presymptomatic, prenatal, susceptibility), nutrigenomics or pharmacogenomicsThis is a dangerous precedence and there are no law yet to cover this.

24Scientific accuracy, clinical validity and utility of genetic testsAbsence of and/or quality of pre- and post-test counsellingAbsence of individualized medical supervisionLack of adequate consent proceduresRespect for privacy and confidentiality

Direct To Consumer (DTC) Screening Tests25What is to be done about direct to consumer (DTC) genetic screening tests?Role of regulating direct to consumer medical tests?Ethical Reflections

Ethical concerns about direct to consumers (DTC) genetic testingScientific accuracy, clinical validity and utility of genetic tests- They analysis everything from real disease causing mutations to gene variants which may or may not affect the risk of having a disease. The risk factors given are not consistent (varies from companies to companies)Absence of and/or quality of pre- and post-test counsellingAbsence of individualized medical supervision. Interpretation is an issue while it is clear cut that you have a gene with a high cancer risk, what does it mean that you have a risk for X which is 4.5 times that of the general population?Lack of adequate consent proceduresRespect for privacy and confidentialityNote: Currently only the United States and New Zealand allow direct-to-consumer advertising of prescription pharmaceuticals

26Medical UtopiasEthical Reflections on Emerging Medical Technologies3. Development of new pharmacotherapeuticsFinancial conflicts of interest have become more common in recent years, as industry has become more involved in research and medical education. Drug and biotechnology companies now finance the majority of clinical trials, up from just 32% in 1980. Financial arrangements take many other forms, including company stock for individual scientists, licensing revenues, donation of funds and equipment to medical schools and hospitals, and positions of influence on advisory boards.Research sponsored by industry tends to produce results that favor the sponsor. Also, those results are likelier to be kept secret. Such biases could produce a body of research results that are unreliable at best and misleading at worst. Recent scandals involving hazardous side effects of the cox-2 inhibitor class of painkillers and other popular medications arose in part because of conflicts of interest between researchers, regulators, and drug companies.Medical research depends on industry funding. The challenge is to find ways to use that funding without harming science and the public.

27Ethical Concerns on Pharmacotherapeutics28Test for carcinogenicityShort term in vitro mutagenicity testLifespan in vivo tests in rodents (two species)12-24 monthsexpensive

Testing of new drugs

Testing for carcinogenicityShort term in vitro mutagenicity testAdds drug to mammalian cells or microorganism in glass dishes to see if it damage or alters the DNA leading to mutation causing mutagenicity.These drugs are called mutagenic carcinogensNon-mutagenic carcinogens are those which do not act on DNA.Lifespan in vivo tests in rodentsNon-mutagenic carcinogens are those who are metabolized in animas to produce a carcinogenic substancesFeeding rodents the drugs over the span of their lifetime 18-24 years.Because of difficulty in extrapolating across species, WHO recommend testing two species- rat and mice.

29International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) approved using genetic engineered rats for one species short term lifespan studies in 1997The validation was done in the 2000s by International Life Sciences Institute (ILSI) Short term lifespan rodent studiesIn July 1997, ICH approved the guidelines for Testing for Carcinogenicity of Pharmaceuticals which proposes a short term rodent lifespan study instead of the long term lifespan studies. This involves three types of genetically engineered rodents (created 1970s). These rodents where oncogenes are introduced or where the tumour suppression genes are removed (knocked out).The ICH decision was based on studies done on three genetic engineered mouse:tgAC mouse -transgenic mice with oncogene (v-Ha-ras) introducedp53 mouse knock out mouse with tumour suppressor gene (p53) removedrasH2 mouse transgenic mouse with oncogene (c-Ha-ras) introduced.In the tgAC student, carcinogens were introduced to the mouse skin. This raised questions as most pharmaceuticals are ingested orally. Only 23 chemicals were used. The approval were given even before the validation studies were done. Results in 8 weeks.The validation was done in the 2000s by International Life Sciences Institute (ILSI). John Abraham and Rachel Ballinger notes that the validation studies were driven by senior scientists from American pharmaceutical firms such as Schering-Plough, Sanofi Sterling Winthrop, Novartis, Johnson & Johnson. Merck, and Pfizer 30How accurate are these studies using genetically engineered rats?How safe are the new drugs?Ethical Reflections31Ethical Concerns on Pharmacotherapeutics32Design of clinical trailsCost as a barrier to accessProfessional standards of care

Ethical Concerns on PharmacogenomicsDesign of clinical trailsAbility to predict drug efficacy by genotyping participants allows researchers to identify those whose genotypes will likely to benefit from the drug allowing smaller, cheaper and faster to run trialsThese drugs are approved and then used for the general populationSafeguardsFDA- require manufacturers to maintain clinical records relevant to determine whether the drug is to be withdrawn and to submit adverse drug reportsEuropean Union (EU) European Agency for the Evaluation of Medicinal Products, and the Commission on Proposed Medicinal Products require reports of adverse reactions to be submitted every six months for two years after approval. Individual members may have their own guidelines that can overrule the European AgencyJapan- Pharmaceuticals Affair Bureau requires report of adverse drug reactions and to submit products for reevaluationCost as a barrier to accessMore profitable to develop resources to develop drugs for the more prevalent genotypesGroups characterized by less profitable genotypes become therapeutics orphans (therapeutics for rare diseases are called orphan drugs.Professional standards of carePhenotyping group based studies often are distributed along ethnic linesAs pharmacogenomics-based drugs increase in prevalence in the coming years, the use of genotyping or genetic testing as a diagnostic toolprescription of medication based on genotypic medication become a standard of care for physiciansPhysicians may be sued if they lack sufficient knowledge to interpret genetic diagnostic tests, prescribe pharmacogenomic-based drug in proper dosage, consider pharmacogenomic-based drug interactions, or properly dispense pharmacogenomic-based drug prescriptions.(2000, four individuals filed a class action against SmithKline Beecham, alleging that the manufacturers of a vaccine against Lyme Disease will cause arthritis in some people because of their genotype but did not warn of this by labelling. Case still pending).

33Medical Utopias and Emerging TechnologiesBeauchamp and Childress; Principles Biomedical Ethics, OUP, 5th edition 2001Respect for AutonomyBeneficenceNon-MaleficenceJustice34

Ethical Reflections35