Can Intelligent Systems be used to Practice Medicine

1. Can Intelligent Systems be used to Practice Medicine? Craig Lucas BSc PhD Senior Analyst, InferMed Ltd GreetingsGreetings

2. Computer Science -> Bioinformatics -> Public Health -> Clinical Practice Hopfield networks operate in a similar manner to DNA strands undergoing point mutations Andy Bulpitt, Computer Vision What is Bioinformatics? “Analysis of biological data with computers”Computer Science -> Bioinformatics -> Public Health -> Clinical Practice Hopfield networks operate in a similar manner to DNA strands undergoing point mutations Andy Bulpitt, Computer Vision What is Bioinformatics? “Analysis of biological data with computers”

3. A Bit More About Me PhD Bioinformatics, University of Leeds, UK (2001—2004) “Protein Function Prediction Using Statistically Significant Substructure Discovery” Proteins are the building blocks of cells, they perform every interesting function in your body. They can be antibodies, enzymes, operate muscle contractions, give pigment to eyes. Each protein is coded for by a gene.Proteins are the building blocks of cells, they perform every interesting function in your body. They can be antibodies, enzymes, operate muscle contractions, give pigment to eyes. Each protein is coded for by a gene.

4. Structural Bioinformatics Circadian clock regulators on left, tumor suppressant on the rightCircadian clock regulators on left, tumor suppressant on the right

5. Gene Analysis “We will be the first company to sequence complete human genomes for less than $1,000 in material costs” Dr. Clifford Reid, Complete Genomics, October 2008 With a full genome sequence, a patient could be screened to determine which proteins their DNA codes for This allows an opportunity for personalised drug targeting, where individuals receive molecules that bind with specific protein regions

6. Bayesian Statistics Thomas Bayes, 1702—1761 Bayes’ Theorem allows us to relate conditional and marginal probabilities: Computer VisionComputer Vision

7. Even More About Me Health Protection Agency, Centre for Infections, Colindale, UK (2005—2007) Bioinformatics Scientist 2D image analysis of underlying 1D data Approximately ten years research gap between the academic and public sector 11 year cycles of sunspots and influenza. Hoping for clarity, but first taste of “the real world”11 year cycles of sunspots and influenza. Hoping for clarity, but first taste of “the real world”

8. Clostridium perfringens -- Johansson et al. BMC Microbiology 2006 6:47 (Salmonella in lane M1) Technical challenges were little compared to the human factor Commercial confidentialityClostridium perfringens -- Johansson et al. BMC Microbiology 2006 6:47 (Salmonella in lane M1) Technical challenges were little compared to the human factor Commercial confidentiality

9. InferMed Ltd Founded in 1999, a spin-off from Cancer Research UK Current staff ~30 London, Boston, Nice, Singapore, New Zealand Key Products: MACRO for electronic data capture Arezzo for clinical decision support

10. InferMed Ltd

11. Big Pharma, US 10—15 years drug development time, at a cost of $1,000,000,000 Cost of bringing a drug to market is approximately 15%—20% of revenue Of every 10,000 compounds screened, 250 enter animal testing 5 enter human trials 1 will get FDA approval $60,000,000,000 per year industry R&D spending

12. Northwick Park TeGenero employed Parexel to test a potential treatment for leukaemia, TGN1412 All subjects were injected within twenty minutes total and suffered a “cytokine storm” “The notes explained how to treat it. But none of the staff appear to have read their own guidelines.” – Gene Matthews, Lawyer TeGenero is no longer in business

13. Keeping Up With Your Reading MEDLINE literature database contains published articles from about 5,000 journals 16,900,815 articles total (1966—present) 13,551 articles added between 2008/09/29 – 2008/10/03 Approximately 1 new article to read every 45 seconds

14. More Can Be Less “…in a culture that tells us that there is no excuse for falling short of perfection when your options are limitless, too much choice can lead to clinical depression.” - Barry Schwartz, “The Paradox of Choice”

15. Less Can Be More Cook County Hospital Chicago Doctors were instructed to gather less data on patients suffering from chest pain Diagnosis of heart attack improved - Malcolm Gladwell, “Blink: The Power of Thinking Without Thinking” Instinct of the individualInstinct of the individual

16. Clinical Guidelines Distill data into simple guidelines NICE National Institute for Clinical ExcellenceDistill data into simple guidelines NICE National Institute for Clinical Excellence

17. Multiple Conditions @neurIST is a European Union project for decision support in cerebral aneurism cases Aneurisms are usually fatal when ruptured, but intervention carries risks too High blood pressure is a key risk factor but many drugs are not suitable with diabetes Need to combine logic from blood pressure guidelines with that of diabetes Clot in blood vessels in the brain In past, symptoms led to examination but now routine head scans reveal dormant aneurismsClot in blood vessels in the brain In past, symptoms led to examination but now routine head scans reveal dormant aneurisms

18. Executable Guidelines PROforma language expresses clinical guidelines in a computer interpretable form Developed at Cancer Research UK, led by Professor John Fox Implemented in InferMed’s Arezzo product PROforma has had numerous successes in real world trials - Fox et al, Informatics in Primary Care 2006; 14:00–00 Now more detail about the language itself…Now more detail about the language itself…

19. Declarative vs Imperative Declarative What we want the computer to do Examples: Prolog SML OCL Imperative How we want the computer to do it Examples: C++ Java Assembly Specify logic of guidelines, then logic of current patient situation Clinicians prefer declarative, as it is closer to their mode of thinking Traditional, Prolog-style, logic not sufficient for this alone. Not just true and false…Specify logic of guidelines, then logic of current patient situation Clinicians prefer declarative, as it is closer to their mode of thinking Traditional, Prolog-style, logic not sufficient for this alone. Not just true and false…

20. True or False? Does the patient have a family history of heart disease? Does the patient’s record show a family history of heart disease? Does the patient’s record show that there is no family history of heart disease? Does the patient’s record lack information on their family history of heart disease? Simple “true” and “false” are not sufficient True and false are not enough, we are dealing here with “belief”. Not probabilities.True and false are not enough, we are dealing here with “belief”. Not probabilities.

21. Modal Logic Reasoning that includes notions of belief Necessarily Possibly A is true A is necessary A is possible Extension of 1st order logic (Socrates is a man, All men are mortal, therefore Socrates is mortal) Safety systems require notions of what is allowableExtension of 1st order logic (Socrates is a man, All men are mortal, therefore Socrates is mortal) Safety systems require notions of what is allowable

22. Deontic Logic It is obligatory that It is permitted that It is forbidden that

23. “Safety” Logic Builds on Deontic logic It is safe that It is authorised that Fox et al, “Safe and Sound: Artificial Intelligence in Hazardous Applications”

24. Advantage of Argumentation Given the current state of the patient, what are the recommended drug prescriptions to lower their blood pressure? Search knowledge base for relevant rules Apply rules, but retain lines of reasoning Clinician can see the logic of the recommendation and overrule if required Bayesian approaches are difficult for clinicians to understandBayesian approaches are difficult for clinicians to understand

25. Decision Making Qualitative reasoning okay, but why not use neural networks to produce qualitative arguments? We have to optimise the inputs to get best results Here’s my suggestion for an “Intelligent System”…Qualitative reasoning okay, but why not use neural networks to produce qualitative arguments? We have to optimise the inputs to get best results Here’s my suggestion for an “Intelligent System”…

26. Decision Support But not everyone agrees this is “decision support”…But not everyone agrees this is “decision support”…

27. “Decision Support” Providing filtered web content Simple rules-based tree navigation Map of Medicine, used in the NHS. Let’s you explore a tree but not go back if something changes or new evidence comes to light. If nobody agrees on what constitutes decision support, then we have a long way to go. But standards bodies are a good place to start…Map of Medicine, used in the NHS. Let’s you explore a tree but not go back if something changes or new evidence comes to light. If nobody agrees on what constitutes decision support, then we have a long way to go. But standards bodies are a good place to start…

28. International Standards HL7 Messaging Refers to level 7 of OSI networking stack Protocol for transmitting healthcare information Allows multi-vendor installations GELLO Standard for querying medical records OCL base language, side-effect free

29. HL7 v3 Message <recordTarget> <patientClinical> <id root="2.16.840.1.113883.19.1122.5“ extension="444-22-2222” signingAuthorityName="GHH Lab Patient IDs"/> <statusCode code="active"/> <patientPerson> <name use="L“> <given>Eve</given> <given>E</given> <family>Everywoman</family> </name> <asOtherIDs> <id extension="AC555444444" assigningAuthorityName="SSN" root="2.16.840.1.113883.4.1"/> </asOtherIDs> </patientPerson> </patientClinical> </recordTarget> So, how are our records stored currently? So, how are our records stored currently?

30. Free Text Terabytes of patient medical records are stored by the NHS as free text Consolidation required to convert data into a form usable by decision support e.g. Microsoft Amalga Detailed ontologies are required to describe medical record content e.g. SNOMED We’re talking about a centralised record system for all of our medical records.We’re talking about a centralised record system for all of our medical records.

31. Recap Personal gene sequences Full medical history Lifestyle choices Family history Knowledge base of drug behaviours Recommended guideline logic All stored centrally, processed by a computer, which then recommends drugs and treatments to give to you

32. Family History Family history vitally important in diagnosing breast cancer and recommending screening With a fully centralised database, is it acceptable to access family medical records to perform a diagnosis? If your parent was keeping a cancer diagnosis to themselves, should they be allowed to keep it secret? Even if it affects your health? There are many who are tempted to opt out of such a system, but their decision potentially affects their children, should they have anyThere are many who are tempted to opt out of such a system, but their decision potentially affects their children, should they have any

33. Health Insurance To ensure a fairer level of insurance cover, would it be acceptable for insurers to access mass statistical data for patients? If you volunteered your data to an insurance company, could they then use your data to assess the risk of family members?

34. Anonymisation Remove name? Remove address? But location can be deduced from GP surgery Home also useful for outbreak tracking Remove date of birth? Age is strongly connected to health diagnoses, yet your DOB plus street name is usually enough to identify you as an individual

35. Data Security HM Revenue and Customs lose discs containing 25m people's details, December 2007 3m drivers details lost by Driving Standards Agency, December 2007 Confidential Home Office data turns up in laptop on eBay, February 2008 Technical solutions already exist for these problems, the difficulty is at the human level

36. Privacy How much information should a doctor be able to access about you at any one time? How about a nurse? How about a pharmacist? Once data gathering really does have a significant effect on public health, will it become socially irresponsible to withhold information?

37. Right of Ignorance With full genome sequencing possible, doctors could have access to a list of likely genetic predispositions you may have Is it always good to know everything? Social and cultural factors are relevant Prospective parents browsing their medical records may want the gender of the unborn baby concealed

38. Accuracy Errors may occur in: Software design Software coding Even very thorough testing Hardware Clinical evidence experiments Clinical evidence reporting Creation of executable guidelines

39. Mitigation Quality controlled software development Checksums and multiple data points Extensive training for guideline authors Risk cannot be reduced to zero

40. Risk No perfect way to provide decision support without risks Are the risks of using the technology outweighed by the risk of not using it? Clinical evidence of drugs and equipment may be applied to software Clinicians should retain responsibility, as they do after reading a flawed text book

41. Challenges Conversion of text-based medical records into computer-processable data Adequate logic paradigm for representation and reasoning with clinical guidelines Data security Hardware infrastructure Software quality standards But it is the social issues that far outweigh the technical challenges

42. Can Intelligent Systems be used to Practice Medicine? Craig Lucas BSc PhD Senior Analyst, InferMed Ltd Can they? Of course! Should they? With the right approach. Will they? Depends on the social factors. Thank youCan they? Of course! Should they? With the right approach. Will they? Depends on the social factors. Thank you