1. BME 301 Lecture Twenty-One

3. How are health care technologies managed? Examples: MRI Laparoscopic cholecystectomy Vitamin C treatment for scurvy Research Funding Regulatory Approval ReimbursementDiffusion

4. Using Gold to Detect Cancer NormalAbnormal How long do you think it will be before we can test this in patients?

5. Using Gold to Feel Better http://www.alchemistsworkshop.com/ http://www.cnn.com/2002/ALLPOLITICS/10/02/ offbeat.blue.candidate/ http://www.cnn.com/2002/ALLPOLITICS/10/02/ offbeat.blue.candidate/ How long do you think it will be before we can test this in patients? http://www.amber.org/~laloca/photos/ra ndom/stanjones.jpg

6. Vitamin-, Mineral-, Herbal-Supplements Thousands sold in the US Remarkably little is known about most http://www.gnc.com/products/ 6 out of 10 Americans take one or more supplements a day Multi-vitamins Amino acids Weight-loss cures Herbal tonics Americans spent $19 billion on dietary supplements in 2003

7. Zantrex-3 One of the most popular weight loss supplements currently sold in the US One month’s supply: $50 Millions of bottles sold Hit US market in March, 2003 Sold at: GNC, CVS, RiteAid, Wal-Mart, internet, eBay Contains: Caffeine Green team Three common South American herbs that act as stimulants

8. http://1800patches.co m/zantrex/combo.ht ml?siteid=ia_cT7QKp QM- fHD1gG4hCzyoEaxIXj DS5g

9. Zantrex Marketing Don Atkinson VP of Sales for Basic Research Company that distributes Zantrex-3 “When I train salespeople, I say to them, ‘Do you know what people are calling you for? It isn’t the pill. They are calling you for hope. That is really what they want from you.’ ” “I love my job. And do you know why? Because when I get up in the morning I know somebody’s life is better because we are here. Somebody today got some hope.”

10. 1994: Dietary Supplement Health & Education Act Congress deregulated supplement industry Companies are not required to prove products are effective or even safe before marketing them Companies CANNOT: Blatantly lie Claim to have a cure for a specific disease (cancer, diabetes, AIDS) Companies CAN say (without evidence): Product is designed to support a healthy heart CardiAll Protect cells from damage Liverite Improve function of compromised immune system Resist Almost no standards that regulate how pills are made Not tested once they are made

11. Benefits of Supplements Vitamin C to prevent scurvy Mid-18 th century: Scurvy killed more British sailors than war Folic acid to prevent neural tube defects Calcium to prevent osteoporosis Vitamin B 12 to prevent dementia

12. History of Supplements 1793: Patent legislation that permitted manufacturers to protect their formulations Did not require that they work Early 1800s: Number of newspapers in US published increased dramatically Early 1900s: Patent-medicine business accounted for more newspaper ads than any other kind of product

13. Lydia Pinkham’s Vegetable Compound “A Positive Cure” for “all those Painful Complaints and Weaknesses so common to our female population” 1914 AMA analyzed Pinkham’s compound 20% pure alcohol 80% pure vegetable extracts Many supplements laced with: Cocaine Caffeine Opium Morphine http://www.lynximages.com/images3/lydia.jpg

15. History of Supplements 1906: Pure Food and Drug Act Reaction to “The Jungle” by Upton Sinclair Permitted Bureau of Chemistry to insure that labels contained no false or misleading advertising http://i.timeinc.net/time/magazine/arc hive/covers/1934/1101341022_400.jp g

16. History of Supplements 1937: Sulfanilimide, antibiotic for streptococcal infections, used safely as a pill for years Most children can’t swallow pills One company in Tennessee found they could dissolve drug in ethylene glycol (antifreeze) Tested for flavor, appearance, fragrance, NOT for toxicity Shipped it all over the country Within weeks, scores of children were dead

17. Sulfanilimide 137 children died Severe abdominal pain, nausea, vomiting, convulsions “Even the memory of her is mixed with sorrow for we can see her little body tossing to and fro and hear that little voice screaming with pain and it seems as though it would drive me insane.” Letter to FDR, from woman describing the death of her child

18. History of Supplements 1938: Food, Drug and Cosmetic Act Gave FDA authority it needed to regulate such products

19. History of Supplements 1940s-1960s: Line between foods and drugs was fairly clear If manufacturers made a disease related claim for a supplement, FDA would go after them 1970s: Government started telling Americans to alter diets if they wanted to have longer, healthier lives Heart disease, diabetes, cancers  eat less salt, fat; add fiber, eat more fruits & vegetables

20. Kellogg’s All Bran 1984: Launched campaign with NCI All-Bran cereal illustrated how low-fat, high- fiber diet might reduce risk of certain cancers http://www.kelloggs.com/brand/allbran/

21. Today CANNOT mention disease CAN make claims that food can affect structure of function of body Examples: CANNOT say that a product reduced cholesterol but CAN say it maintains healthy cholesterol levels CANNOT say echinacea cures disease, but CAN say it has natural antibiotic activities and is considered an excellent herb for infections of all kinds

22. Echinacea One of the most commonly used cold remedies in US Clinical Trial: 400 children with common colds over 4 months Compared placebo to echinacea Placebo worked just as well Children taking echinacea were more likely to develop a rash http://www.kalyx.com/store/images/208 093.jpg

23. Ephedra Was most popular supplement in US Brought in more than $1B/year 10% of supplement industry annual sales Risks of ephedra use (when used with caffeine): Increased risk of heart attack, stroke, palpitations, anxiety, psychosis, death Steve Belcher 23 year old pitcher for Baltimore Orioles Died February, 2003 of heatstroke following taking an over-the-counter product that contained ephedra http://www.cnn.com/2003/HEALTH/12/30/cnna. thompson/ http://www.cnn.com/2003/HEALTH/12/30/cnna. thompson/

24. Today Congress: Considering a bill that would modify 1994 law so that many unregulated botanical supplements would be treated more like drugs than like foods Supplement manufacturers: Assault on first amendment “We put disclaimers in our ads, and we give people the results of the studies and a money-back guarantee. What more could you want? Don’t prevent people from using their judgment. Let them try it. If it doesn’t work, they can return it. That’s what’s fair. That’s what’s American.”

25. Misfortune, disaster, & tragedy Lead to reforms in drug and device regulation

26. FDA Regulates products whose annual sales account for ¼ of consumer spending in US Responsible for ensuring SAFETY and EFFICACY of CHEMICAL, BIOLOGICAL agents and sophisticated medical DEVICES Safe: Probable benefits to health for intended use outweigh any probable risk of harm Effective: Device does what it is supposed to do in a reliable fashion

27. History of Regulation 1906 First federal regulation of drugs Food and Drugs Act 1938 Food, Drug and Cosmetic Act 1962 Drug amendments to FD&C Act 1976 Medical Device Amendments to FD&C Act

28. 1906 Food and Drug Act Label could not contain any statement regarding therapeutic effect which is false and fraudulent FDA could act only after drugs were marketed Was not enough to show that product did not work Had to show that seller knew the claims it made were false

29. 1938 Food, Drug and Cosmetic Act New Drugs: Could not be marketed without first notifying the FDA and allowing agency time to assess safety Beginning of era in which it is illegal to market a new drug without FDA approval Seller’s belief regarding product’s value was no longer relevant Issue – does the product really work?

30. 1962 Drug Amendments to FD&C Act: FDA must review evidence of drug safety and effectiveness Converted pre-market notification system into pre-market approval system Evidence of safety and efficacy must come from well-controlled investigations by qualified experts FDA has the authority to prevent harm before it occurs

31. Drug Approval Process Pre-clinical testing (cell, animal) occurs first Assess toxicity Investigational New Drug (IND) Human clinical trials allowed with IND Phase 1, 2, 3 clinical trials Manufacturer files NDA (New Drug Application) for permission to market new drug

33. Phases of Clinical Trials Phase 1: Goal: safety of compound Low doses administered to small group of healthy volunteers 20-100 volunteers Phase 2: Goal: effectiveness of compound 100-300 patients who suffer from condition Phase 3: Final step before seeking FDA approval Randomized clinical trial

34. Post-Market Surveillance Phase 4: Study longer term effects of drug exposure Report adverse effects to FDA

35. Not Many Drugs Make It For every 5,000-10,000 drugs that enter pre-clinical testing ONE makes it to market Cost of developing one new drug: $360 million-$500 million

36. Regulation of Medical Devices FDA did not regulate devices before 1938 1938: FDA could only challenge sale of products it believed were unsafe Could only remove them from the market after patient injuries 1960s: Rapid innovation in medical technology Tried to regulate many as drugs: contact lenses, IUDs Catastrophic failures of heart valves and pacemakers 1970s: Broad recognition that different rules were needed to regulate devices

37. 1976 Device amendments to FD&C Act: No single policy would work for all devices Tongue depressor Artificial heart

38. 1976: Device amendments to FD&C Act Three classes of devices: Class I: Pose least risk to patient Not life sustaining GMP, proper record keeping required 30% of devices X-ray film, tongue depressors, stethoscopes Class II: Not life sustaining, but must meet performance standards Blood pressure monitors, Catheter guide wires 60% of devices Class III: Pose greatest risk to patient For use in supporting or sustaining human life 10% of devices Stents, heart valves, LVADs Require GMP, failure modes analysis, animal tests, human clinical studies under IDE

39. Role of CDRH Ensure that products coming to market have more benefit than risk Ensure that products are labeled so that practitioners and patients know what to expect from their use Regulates 1,700 types of devices 23,000 registered manufacturers 1996: received 20,236 device related submissions

40. Device Approval Process Device + intended use considered together Manufacturer submits request for marketing approval Advisory panel: One consumer representative (non-voting) One industry representative (non-voting) Physicians and scientists FDA not required to follow recommendations of panel, although they usually do

41. IDE Investigational Device Exemption Enables experimental use of high risk device Must have positive engineering and animal data First give approval for feasibility studies with small number of patients Then proceed to multi-center trials Larger data sets frequently show results from small sample sets are not true

42. Humanitarian Use Exemption Device designed to treat or diagnose condition that affects <4,000 patients/year Device would not otherwise be available without exemption No comparable device is available Patients will not be exposed to unreasonable or significant risk of injury or illness by device

43. Medical Device Reporting System to detect device related problems in a timely manner Serious injuries or deaths that may have been caused by or related to a a medical device must be reported to the manufacturer of the device within 10 days Must be reported to the FDA within 10 days

44. Assignments Due Next Time HW9