0
Adverse drug reactions: the role of case reports Jeff Aronson Reader in Clinical Pharmacology,  Department of Primary Heal...
 
Types of adverse drug reactions reports in the world literature
Reasons for publishing anecdotes of adverse drug reactions <ul><li>Reason   Examples </li></ul><ul><li>Newly recognized AD...
Reports of suspected adverse effects of mestranol and ethinylestradiol to the then Committee on Safety of Drugs 942 report...
Products containing considerable amounts of glycyrrhizinic acid Confectionery: Liquorice all sorts Torpedos Blackcurrant P...
Reasons for publishing anecdotes of adverse drug reactions <ul><li>Reason   Examples </li></ul><ul><li>Newly recognized AD...
Joseph Berkson (1899-1982) “ Scientist, statistical philosopher, innovator, and much loved curmudgeon” Logit (J Am Stat As...
Between-the-eyes adverse effects
Between-the-eyes adverse effects 1. Extrinsic or intrinsic tissue deposition of the drug or a metabolite   Intrinsic: Depo...
Eiferman et al. Ciprofloxacin microprecipitates and macroprecipitates in the human corneal epithelium. J Cataract Refract ...
Between-the-eyes adverse effects 1. Extrinsic or intrinsic tissue deposition of the drug or a metabolite  2. A specific an...
Brazier et al. Ecstasy related periodontitis and mucosal ulceration—a case report. Br Dent J 2003; 194(4): 197-9
Between-the-eyes adverse effects 1. Extrinsic or intrinsic tissue deposition of the drug or a metabolite  2. A specific an...
Between-the-eyes adverse effects 1. Extrinsic or intrinsic tissue deposition of the drug or a metabolite  2. A specific an...
Trevenzoli et al. Sepsis and granulomatous hepatitis after bacillus Calmette-Guérin intravesical installation.  J Infect 2...
A crime scene analogy Distinctive outcome  Recognizing a modus operandi Culprit’s fingerprints found at the scene of the c...
 
Comprehensiveness and adverse  effects of amiodarone <ul><li>Site of ADR </li></ul><ul><li>Heart </li></ul><ul><li>Thyroid...
http://www.who-umc.org Database of 4.7 million case reports 94 countries 300,000 new records per year
<ul><li>Quantitative & automated numerator-based statistical methods producing  relative reporting rates </li></ul><ul><li...
 
Proportional Reporting Ratio (PRR) Produces a numerical “signal score” by which drug-event pairs can be ranked D C All adv...
Statistics in Medicine 2009; 28: 1774–92
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Comprehensive reporting of suspected adverse effects Age Sex Weight Ethnicity Diagnoses Allergies Drug treatment (current/...
Aronson, BMJ 2003; 326: 1346; e-appendix
<ul><li>Title </li></ul><ul><li>Structured summary </li></ul><ul><li>Introduction </li></ul><ul><li>The case report </li><...
Discussion Likelihood of a true association Reasons for implicating the drug Why other drugs were not responsible Eliminat...
 
Conclusions Anecdotal reports of suspected adverse drug reactions make up a large propotion of the published literature A ...
Raymond Wolfinger:  “ The plural of anecdote is data”
Upcoming SlideShare
Loading in...5
×

Adverse drug reactions: the role of case reports - Jeff Aronson

1,190

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
1,190
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
40
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Transcript of "Adverse drug reactions: the role of case reports - Jeff Aronson"

  1. 1. Adverse drug reactions: the role of case reports Jeff Aronson Reader in Clinical Pharmacology, Department of Primary Health Care, Oxford President, British Pharmacological Society Meyler’s Side Effects of Drugs Side Effects of Drugs Annuals Editor-in-Chief
  2. 3. Types of adverse drug reactions reports in the world literature
  3. 4. Reasons for publishing anecdotes of adverse drug reactions <ul><li>Reason Examples </li></ul><ul><li>Newly recognized ADR Oculomucocutaneous syndrome (practolol) </li></ul><ul><li>Generate hypotheses Teratogenicity (antihistamines) </li></ul><ul><li>Test hypotheses Loading dose in renal insufficiency (digoxin) </li></ul><ul><li>Diagnostic tests Lung damage (KL6) (amiodarone) </li></ul><ul><li>Elucidate mechanisms Torsade de pointes/QT  (antiarrhythmics) </li></ul><ul><li>Methods of management Self-poisoning (verapamil) </li></ul><ul><li>Systematic review Thromboembolism (mestranol) </li></ul><ul><li>Remind and educate Hypokalaemia (liquorice) </li></ul>
  4. 5. Reports of suspected adverse effects of mestranol and ethinylestradiol to the then Committee on Safety of Drugs 942 reports 88 PEs 854 others Inman, WH. “Don’t Tell the Patient”, 1999 63 441 Mestranol 25 413 Ethinylestradiol
  5. 6. Products containing considerable amounts of glycyrrhizinic acid Confectionery: Liquorice all sorts Torpedos Blackcurrant Pomfret (Pontefract) cakes Servez vous Sorbits chewing gum Stimorol chewing gum All types of liquorice root: Russian, Iranian, Chinese, Turkish, Afghan, and unknown origin Health products: Liquirizia naturale Liquorice flavoured diet gum Throat pearls Liquorice flavoured cough mixtures Herbal cough mixtures Antibron tablets Liquorice tea Chewing tobacco Alcoholic drinks: Belgian beers, pastis, anisettes–raki, ouzo, Pernod
  6. 7. Reasons for publishing anecdotes of adverse drug reactions <ul><li>Reason Examples </li></ul><ul><li>Newly recognized ADR Oculomucocutaneous syndrome (practolol) </li></ul><ul><li>Generate hypotheses Teratogenicity (antihistamines) </li></ul><ul><li>Test hypotheses Loading dose in renal insufficiency (digoxin) </li></ul><ul><li>Diagnostic tests Lung damage (KL6) (amiodarone) </li></ul><ul><li>Elucidate mechanisms Torsade de pointes/QT  (antiarrhythmics) </li></ul><ul><li>Methods of management Self-poisoning (verapamil) </li></ul><ul><li>Systematic review Thromboembolism (mestranol) </li></ul><ul><li>Remind and educate Hypokalaemia (liquorice) </li></ul>Proof
  7. 8. Joseph Berkson (1899-1982) “ Scientist, statistical philosopher, innovator, and much loved curmudgeon” Logit (J Am Stat Assoc 1944; 39: 361) Berkson’s bias (Biometrics Bull 1946; 2: 47-53) Berkson [regression] error model (J Am Stat Assoc 1950; 45: 164-80) Interocular traumatic impact
  8. 9. Between-the-eyes adverse effects
  9. 10. Between-the-eyes adverse effects 1. Extrinsic or intrinsic tissue deposition of the drug or a metabolite Intrinsic: Deposition in nails, teeth Corneal microprecipitates Crystal-storing histiocytosis
  10. 11. Eiferman et al. Ciprofloxacin microprecipitates and macroprecipitates in the human corneal epithelium. J Cataract Refract Surg 2001; 27(10): 1701-2
  11. 12. Between-the-eyes adverse effects 1. Extrinsic or intrinsic tissue deposition of the drug or a metabolite 2. A specific anatomical location or pattern of injury Cytotoxic drug extravasation Intrathecal administration Oral ulceration Oesophageal ulceration
  12. 13. Brazier et al. Ecstasy related periodontitis and mucosal ulceration—a case report. Br Dent J 2003; 194(4): 197-9
  13. 14. Between-the-eyes adverse effects 1. Extrinsic or intrinsic tissue deposition of the drug or a metabolite 2. A specific anatomical location or pattern of injury 3. Physiological dysfunction or direct tissue damage demonstrable by physicochemical testing Oligohidrosis Photosensitivity Taste disturbance Dry mouth
  14. 15. Between-the-eyes adverse effects 1. Extrinsic or intrinsic tissue deposition of the drug or a metabolite 2. A specific anatomical location or pattern of injury 3. Physiological dysfunction or direct tissue damage demonstrable by physicochemical testing 4. Infection, due either to the administration of an infective agent as the therapeutic substance or to demonstrable contamination BCG, mumps
  15. 16. Trevenzoli et al. Sepsis and granulomatous hepatitis after bacillus Calmette-Guérin intravesical installation. J Infect 2004; 48(4): 363-7
  16. 17. A crime scene analogy Distinctive outcome Recognizing a modus operandi Culprit’s fingerprints found at the scene of the crime Infection-related Culprit incriminated by recreating the crime scene Physicochemical dysfunction or tissue damage Culprit caught at the scene of the crime and seen committing it Specific anatomical location or pattern of injury Culprit caught at the scene of the crime Extracellular or intracellular tissue deposition Crime scene analogy Category
  17. 19. Comprehensiveness and adverse effects of amiodarone <ul><li>Site of ADR </li></ul><ul><li>Heart </li></ul><ul><li>Thyroid </li></ul><ul><li>Respiratory </li></ul><ul><li>Nervous system </li></ul><ul><li>Liver </li></ul><ul><li>Gastrointestinal </li></ul><ul><li>Eyes </li></ul><ul><li>Skin </li></ul>Meta-analysis (n = 4153) 1.80 1.20 1.00 0.96 0.49 0.47 0.47 0.35 Anecdotes (n = 357) 0.11 0.44 1.00 0.46 0.26 0.02 0.10 0.26 UMC (n = 7043) 0.44 1.70 1.00 0.89 0.77 0.49 0.20 1.04 Loke, Derry, Aronson Br J Clin Pharmacol; 2004: 57: 616-21
  18. 20. http://www.who-umc.org Database of 4.7 million case reports 94 countries 300,000 new records per year
  19. 21. <ul><li>Quantitative & automated numerator-based statistical methods producing relative reporting rates </li></ul><ul><li>In principle these methods aim to answer the question: Are adverse events reported with the drug at a disproportionately high rate? </li></ul><ul><li>A disproportionately high reporting rate of a drug-event pair does not necessarily betoken a causal relation </li></ul><ul><li>Therefore these methods need to be accompanied by clinical evaluation and subsequent verification </li></ul>
  20. 23. Proportional Reporting Ratio (PRR) Produces a numerical “signal score” by which drug-event pairs can be ranked D C All adverse events reports in database B A Reports of the event of interest All other drugs in database Drug under review PRR = A / C B / D
  21. 24. Statistics in Medicine 2009; 28: 1774–92
  22. 39. Comprehensive reporting of suspected adverse effects Age Sex Weight Ethnicity Diagnoses Allergies Drug treatment (current/past) Family history Social history Severity Time-course Withdrawal Rechallenge Diagnostic tests Plasma concentrations Animal/in vtiro evidence Treatment Outcome Assessment of likelihood Drug Points in BMJ January 2001 to October 2002 (BMJ 2003; 326: 1346) 35 reports; 48 patients Of 19 desiderata: 9 (5-12) Of 14 yellow card items: 9 (4-12) Of 14 MedWatch items: 8 (3-11)
  23. 40. Aronson, BMJ 2003; 326: 1346; e-appendix
  24. 41. <ul><li>Title </li></ul><ul><li>Structured summary </li></ul><ul><li>Introduction </li></ul><ul><li>The case report </li></ul><ul><ul><li>Demographic information </li></ul></ul><ul><ul><li>Diagnoses </li></ul></ul><ul><ul><li>Drug therapy </li></ul></ul><ul><ul><li>Other relevant history </li></ul></ul><ul><li>The adverse event </li></ul><ul><li>Treatment </li></ul><ul><li>Discussion </li></ul>
  25. 42. Discussion Likelihood of a true association Reasons for implicating the drug Why other drugs were not responsible Elimination of other possible causes Review of previous cases Methods of diagnosis Possible mechanisms Possible forms of management Implications for clinical practice Hypotheses generated
  26. 44. Conclusions Anecdotal reports of suspected adverse drug reactions make up a large propotion of the published literature A few drug-event pairs are interocular Most drug-event pairs are not and need large numbers of reports for signal detection Signals can be detected from accumulated anecdotes; they should then be interpreted clinically and verification attempted The quality of reporting is currently poor and should be improved; guidelines may help
  27. 45. Raymond Wolfinger: “ The plural of anecdote is data”
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×