*******************************************************************************************
A Message for J-PEM from Professor R D Mann，the second Director of
the DSRU in the UK.(25/03/99)

We have continued to build upon the foundations laid by Professor Inman and
have now completed no less than 65 studies undertaken by PEM and with an average
cohort size of 11055 patients. This has produced a very substantial and very rich
computerised database which can be used not only to look at the date on the
individual 65 drugs but also at many diseases.

The richness of the database is shown by the fact that over the last five years we have
made 69 contributions to the world literature on drug safety and 33 of these
contributions represent published papers in peer reviewed journals.

Examples of these publications which show the value of building up a database of this
kind and conducting Prescription-Event Monitoring on newly launched drugs are the
following:

1) A paper describing PEM and its method : Mann RD, Prescription-Event
Monitoring- Recent progress and future horizons.Brit J Clin Pharmacol.1998;46
:195-201.2

2) A recent paper giving an example of Prescription-Event Monitoring on
a specific drug: Mackay FJ,Wilton LV , Perce GL , Freemantle SN and MannRD. The
Safety of Risperidone : a Post-Marketing Study on 7684 Patients. Hum
Psychopharmacol Clin Exp. 1998;13:413-8.

3) A paper showing how PEM can test whether drugs are safe in pregnancy :
Wilton L , Pearce G, Martin RM, Mackay FJ and Mann RD. The outcomes of
pregnancy in women exposed to newly marketed drugs in general practice in England.
Br J Obstet Gynaecol.1998;105:882-9.

4) A paper showing how the database can be used to investigate signals raised by
PEM and then tested by further statistical study : Martin RM, Dunn NR, Freemantle
SN and Mann RD. The risk of non-fatal congestive cardiac failure and ischaemic heart
disease with B2-agonists.Thorax. 1998;53:558-62.

Professor Kubota made a substantial contribution to the establishment of PEM in
England during his stay at the DSRU and we wish him every success in establishing
PEM in Japan.
*******************************************************************************************

*******************************************************************************************
An updated message from Doctor Saad A W Shakir, Director of the DSRU
since July 1997. (10/08/00)

We now have 74 completed PEM studies with an average cohort size of 10844 patients.
There are also eight PEM studies in progress and a further five planned to start during the next
four months.Since the report from the previous director (25/03/99) we have published another
17 papers (see references numbered 70-86 below) and made many contributions to concurrently
with the PEM studies. In particular we are using the database to investigate alternative methods of
signal generation.

From the beginning of this year the DSRU has been using a new computer system which uses the
scanned image of the green form questionnaire for coding and retrieval. The whole database(PEMBase)
has been converted to the new system and the new software allows more information to be captured
and will give the unit more oppotunities for research and analysis.
*******************************************************************************************

DSRU PUBLICATIONS 1994-2000 (28/07/00)

1. Mann RD. Results of prescription-event monitoring study of salmeterol. BMJ.
1994;309:1018.

2. Mann RD. Epidemiologic study system : Prescription-Event Monitoring in the UK.
Southampton Medical Jounal. 1994; 10: 12-7.

3.Miwa LJ, Jones JK, and Mann RD. Identifying resources for assessing use and
effects of pharmaceuticals and other medical products in the European Community.
In: European Medicines Research. Ed: GN Fracchia. IOS Press. 1994; 391-407.

4. Mann RD. Pharmacoepidemiology and the Pharmaceutical Industry. In: Discovering
New Medicines. Careers in Pharmaceutical Research and Development.
Ed: Peter D Stonier. John Wiley & Sons Ltd, UK. 1994; 214-8.

5. Mann RD. Monitoring the Safety of Medicines. In: Clinical Research Manual. Eds:
D Luscombe and PD Stonier. Euromed Communications. 1994; 8: 1-42.

6. Mann RD. Databases and drug epidemiology - the situation in the UK. Eur J Clin
Research. 1994; 6: 92-104.

6-2. Kubota K, Inman WHW. Terminology in Prescription-Event Monitoring.Eur J
Clin Pharmacol. 1994; 46: 497-500.

7. Kubota K, Pearce GL and Inman WHW. Vasodilation - related adverse events in
diltiazem and dihydropyridine calcium antagonists studied by prescription-event
monitoring. Eur J Clin Pharmacol. 1995; 48: 1-7.

8. Mann RD. Guest Editoril. Breast Implants: The tyranny of the anecdote. J Clin
Epidemiol. 1995; 48: 504-6.

9. Mann.RD. Editorial. Festina lente. Pharmacoepidemiology and Drug Safety.
1995; 4: 1-2.

10.Mann.RD. Editorial. Pharmacoepidemiology and Drug Safety. 1995; 4: 125-6.

11.Mann.RD. Essay: Databases, privacy, and confidentiality - the sffect of proposed
new legislation on pharmacoepidemiology and drug safety monitoring. In: Side Effects
of Drugs, Annual 18 (1994). Eds: JK Aronson and CJ van Boxtel. Elsevier, Amsterdam.
1994; xxi-xxxv.

12.Mann.RD. Adverse Drug Reactions and the Adrenal Glands - A Pharmaco-
epidemiological Approach. In: The Adrenal in Toxicology Target Organ and Modulation
of Toxicity. Ed: P Harvey. Taylor & Francis, London. 1995. 279-300.

12-2.Kubota K, Kubota N, Pearce GL, Prescott P and Mann RD. Signalling drug-induced
rash with 36 drugs recently marketed in the United Kingdom and studied by
Prescription-Event Monitoring. Int J Clin Pharmacol Ther. 1995; 33: 219-225.

13.Mann.RD. The Regulation of Drugs in Europe and the United Kingdom. In: Applied
General Toxicology. Ed: Paul Turner. Oxford University Press.

14.Mann.RD. Drug-induced disorders of central nervous function. In: Iatrogenic Diseases.
Ed: PFD'Arcy and JP Griffin. Oxford Medical Publications.

15.Mann.RD. Kubota K, Pearce GL and Wilton LV. Salmeterol: A Study by Prescription-
Event Monitoring in a UK Cohort of 15, 407 Patients. J Clin Epidemiol. 1996; 49: (2),
247-50.

16.Wilton LV. Pearce GL and Mann.RD. A comparison of ciprofloxacin, norfloxacin,
ofloxacin, azithromycin and cefixime examined by observational cohort studies.
Br L Clin Pharmacol. 1996; 41: 277-84.

17.Wilton L, Pearce G, Edet E, Freemantle S, Stephens MDB and Mann.RD. The safty
of finasteride used in benign prostatic hypertrophy: a non-interventional observational
cohort study in 14772 patients. Br J Urol. 1996; 78: 379-84.

18.Mann.RD. Prescription-Event Monitoring and the Reporting of ADR's. A BMA policy
document. 1996: 20-4.

19.Wilton LV. Pearce G and Mann.RD. Cough with ACE Inhibitors: An Example of
Reporting Bias in Observational Cohort Studies. 12th International Conference on
Pharmacoepidemiology, The Netherlands. Pharmacoepidemiology & Drug Safty. 1996;
5: Suppl. 1. Abstract No. 030.

20.Wilton LV, Edet E and Mann.RD. Are Any of the Newer Anti-Epileptic Drugs
Teratogenic? 12th International Conference on Pharmacoepidemiology, The
Netherlands. 1996; 5: Suppl. 1. Abstract No. 032.

20-2.Andrew JE, prescott P, Smith TMF, Inman WHW and Kubota K. Testing for adverse
reactions using prescription event monitoring. Statistics in Medicine. 1996; 15: 987-1002.

20-3.Kubota K, Kubota N, Pearce GL and Inman WHW. ACE-inhibitor-induced cough, an
adverse drug reaction unrecognised for several years: Studies in Prescription-Event
Monitoring. Eur J Clin Pharmacol. 1996; 49: 431-7.

21.Edwards JG, Inman WHW, Wilton L, Pearce GL and Kubota K, Drug Safety
Monitoring of 12692 Patients Treated with Fluoxetine, Human Psychopharmacology
1997; 12: 127-37.

22.Wager E, Tooley PJH, Pearce GL, Wilton LV and Mann.RD. A comparison of two
cohort studies evaluating the safety of cisapride: Prescription-Event Monitoring and
a large phase Ⅳ study. Eur J Clin Pharmacol. 1997; 52: 87-94.

23.Mackay FJ, Wilton LV. Pearce GL, Freemantle SN and Mann RD. Safety of Long-Term
Lamotrigine in Epilepsy. Epilepsia. 1997; 38: (8), 881-6.

24.Mann.RD. Drug Safety and Pharmacovigilance. In: Integrated Pharmacology Eds.
CP Page, MJ Curtis, MC Sutter, MJA Walker, BB Hoffmann. Mosby International,
London. 1997, 6: 83-90.

25.Freemantle SN, Pearce GL, Wilton LV, Mackay FJ and Mann RD. The incidence of
the most commonly reported events with 40 newly marketed drugs - a study by
Prescription-Event Monitoring. Pharmacoepidemiology & Drug Safety. 1997; 6:
Suppl.1.1-8.

26.Stephens MDB, Wilton LV. Pearce GL and Mann RD. Visual Field Defects in Patients
Taking Vigabatrin. 13th International Conference on Pharmacoepidemiology & Drug Safty.
1997; 6: Suppl.2. Abstract No. 041

27.Dunn N. Wilton LV, Pearce G and Mann RD. The Incidence of Hallucinations Associated
with Tramadol. 13th International Conference on Pharmacoepidemiology, Florida,
Pharmacoepidemiology & Drug Safty. 1997; 6: Suppl.2. Abstract No. 042

28.Mackay F, Wilton LV. Pearce G, Freemantle S and Mann RD. Acarbose and
Gastrointestinal Intolerance.13th International Conference on Pharmacoepidemiology,
Florida, Pharmacoepidemiology & Drug Safty. 1997; 6: Suppl.2. Abstract No. 044

29.Mann.RD. William Withering and Lisbon. Pharmacoepidemiology & Drug Safty.
1997; 6: Suppl.3. S1-S4.

30.Mann.RD. Wilton LV. Pearce GL, Mackay FJ and Dunn NR. Prescription-Event Monitoring
(PEM) in 1996 - A Method of Non-Interventional Observational Cohort Pharmacovigilance.
Pharmacoepidemiology & Drug Safty. 1997; 6: Suppl.3. S5-S11.

31.Mackay FJ, Dunn NR, Wilton LV, Pearce GL, Freemantle SN and Mann.RD. A Comparison
of Fluvoxamine, Fluoxetine, Sertraline and Paroxetine Examined by Observation Cohort
Studies. Pharmacoepidemiology & Drug Safety. 1997; 6: No.4. 235-46.

32.Dunn NR, Thorogood M, DeCaestecker L and Mann RD. Myocardial Infarction and Oral
Contraceptives, a Retrospective Case Control Study in England and Scotland ('MICA' Study).
Pharmacoepidemiology & Drug Safty. 1997; 6: No.4. 283-9.

33.Dunn N, Thorogood M, deCaestecker L. Oral contraceptives and myocardial infarction.
Br J Family Planning.

34.Martin RM, Kapoor KV, Wilton LV and Mann RD. Underreporting of suspected adverse
drug reactions to newly marketed, black triangle drugs in general practice. BMJ. 1998;
317: 119-20.

35.Mann.RD. Prescription-Event Monitoring-recent progress and future horizons.
Br J Clin Pharmacol. 1998; 46: 195-201.

36.Dunn NR, Freemantle SN, Pearce GL and Mann RD. Galactorrhoea with moclobemide.
Lancet, Feb. 1998; 351: 802.

37.Mackay FJ, Wilton LV, Pearce GL, Freemantle SN and Mann RD. United Kingdom
experience with alendronate and oesophageal reactions. Br J Gen Pract. April 1998;
48:1161-2.

38.Mann RD. A memorable letter.The ethos of drug safety monitoring. BMJ. 1998;
316: 837.

39.Dunn NR, White I, Freemantle S and Mann RD. The Role of Prescribing and
Referral Bias in Studies of the Association Between Third Generation Oral
Contraceptives and Increased Risk of Thromboembolism.
Pharmacoepidemiology & Drug Safty. 1998; 7: 3-14.

40.Dunn N, deCaestecker L, Bigrigg A. Oral Contraceptives and Thrombosis.
Curr Opin Obstet Gynaecol. 1998; 10: 205-9.

41.Mackay F, and Mann RDM. Letter: Figures given in letter were prevalences,
not incidences. BMJ. 1998; 326: 1390.

42.Dunn N, Pickering R. Does good practice organization improve the outcome
of care for diabetic patients? Br J Gen Pract. May 1998; 48: 1237-40.

43.Wilton LV, Freemantle SN, Martin R and Mann RD. Is the Incidence of Upper
Respiratory Tract Infection Independent of Drug Treatment in Large Cohort Studies
of Longer Term Use Drugs? Pharmacoepidemiology & Drug Safty. ESOP
Supplement. Aug 1998; 7: Supp 1.S4-10.

44.Martin RM, Wilton LV, Mann RD, Steventon P and Hilton SR. Unlicensed and off
label drug use for paediatric patients. BMJ. Letter. 1998; 317: 204.

45.Martin RM, Dunn NR, Freemantle SN and Mann RD. The risk of non-fatal
congestive cardiac failure and ischaemic heart disease with B2-agonists.Thorax.
1998; 53: 558-62.

46.Martin R, When to use a new drug. Aust Prescriber. 1998; 21: No.3; 67-9.

47.Martin RM, Lim AG, Kerry SM and Hilton SR. Trends in Prescribing H2-reception
Antagonists and Proton Pump Inhibitors in Primary Care. Alimentary Pharmacology
& Therapeutics. 1998; 12: 797-805.

48.Martin R, Dunn N, Mann R and Freemantle S. Letter to Editor. Authors' reply.
Thorax. 1998; 53: 1094-5.

49.Martin R, Dunn N, Freemantle S and Mann R. Are common adverse events
reported with the same frequency in patients taking omeprazole compared with
patients taking lansoprazole in general practice in English? 14th International
Conference on Pharmacoepidemiology, Berlin. Pharmacoepidemiology & Drug Safty.
1998; 7: Suppl. 2, S122. Abstract No.100.

50.Martin R, Pearce G, Freemantle S and Mann R. Age and sex specific asthma
death rates in patients taking long acting β2-agonists. 14th International
Conference on Pharmacoepidemiology, Berlin. Pharmacoepidemiology & Drug Safty.
1998; 7: Suppl. 2, S122. Abstract No.101.

51.Mackay F, Martin R, Pearce G, Freemantle S and Mann R. Newer antidepressants:
a comparison of tolerability. 14th International Conference on Pharmacoepidemiology,
Berlin. Pharmacoepidemiology & Drug Safty. 1998; 7: Suppl. 2, S124. Abstract No.106.

52.Mann R, Dean A, Mackay F and Bourke A. Study to Determine the Relationship
Between Prescribed and Dispensed Drugs as Recorded in a Selection of Computerized
General Practices. 14th International Conference on Pharmacoepidemiology, Berlin.
Pharmacoepidemiology & Drug Safty. 1998; 7: Suppl. 2, S195. Abstract No.274.

53.Wilton L, Pearce G, Martin RM, Mackay FJ and Mann RD, The outcomes of pregnancy
in women exposed to newly marketed drugs in general practice in England. Br J Obstet
gynaecol. 1998; 105: 882-9.

54.Mackay FJ, Wilton LV, Pearce GL, Freemantle SN and Mann RD. The Safety of
Risperidone: a Post-Marketing Study on 7684 Patients. Hum Psychopharmacol Clin
Exp. 1998; 13: 413-8.

55.Mackay FJ. Post-Marketing Studies. The Work of the Drug Safety Research Unit.
Drug Safety 1998 Nov; 19: (5): 343-353.

56.Martin RM, Biswas PN, Freemantle SN, Pearce GL and Mann RD. Age and sex
distribution of suspected adverse drug reactions to newly marketed drugs in general
practice in England: analysis of 48 cohort studies. Br J Clin Pharmacol. 1998; 46: 505-51.

57.Mann RD. Adverse reactions and the science of pharmacosurveillance. Eur Respir
Rev. 1998; 8: 63, 1051-3.

58.Mann RD. Pharmacovigilance-The place and usefulness of observational cohort
studies. Bratislava Medical Journal. Bratisl Lek Listy 1998; 99: Suppl. 13-8.

58A.Martin RM, Lunec SG and Rink E. UK postal survey of pharmacists working
with general practices on prescribing issues: characteristics, roles and working
arrangements. Int J Pharm Pract. 1998; 6: 133-9.

59.Mackay FJ, Pearce GL and Mann RD. Cough and angiotensinⅡ inhibitors: cause
or confounding? Br J Clin Pharmacol. 1999; 47: 111-4.

60.Martin RM, Mann RD, Hands DE, Tomlin M and Emerson A. Design of a pilot prospective
cohort study of adverse events monitored by hospital pharmacists. Int J Pharmaceutical
Med. 1999; 13: 11-6.

61.Wilton LV, Stephens MDB and Mann RD, Interim Report on the Incidence of
Visual Field Defects in Patients on Long Term Vigabatrin Therapy.
Pharmacoepidemiology & Drug Safty. 1999; 8: Suppl 1, S9-14.

62.Wilton LV, Pearce G and Mann RD, The Use of Newly Marketed Drugs in
Children and Adolescents Prescribed in General Practice.
Pharmacoepidemiology & Drug Safty. 1999; 8: Suppl 1, S37-45.

63.Dunn N, Freemantle S and Mann R. Nicorandil and diabetes: A nested case-
control study to examine a single generated by prescription-event monitoring.
Eur J Clin Pharmacol. 1999; 55: 159-62.

64.Martin RM, Wilton LV and Mann RD. Prevalence of Churg-Strauss Syndrome,
Vasculitis, Eosinophilia and Associated Conditions: Retrospective Analysis of
58 Prescription-Event Monitoring Cohort Studies. Pharmacoepidemiology &
Drug Safty. 1999; 8: 179-89.

65.Dunn N, Thorogood M, Faragher B, deCaestecker L, MacDonald T, McCollum
C, Thomas S and Mann R,. Oral contraceptives and myocardial infarction:
results of the MICA case-control study. BMJ. 1999; 318: 1579-84

66.Dunn N, Freemantle S, Pearce G, Wilton L and Mann RD. Safty Profile of
Nicorandil-Prescription-Event Monitoring(PEM) Study.
Pharmacoepidemiology & Drug Safty. 1999; 8: 197-205.

67.Mann RD and Bertelsmann A. The Issue of Data Privacy and Confidentiality in
Europe-1998. Pharmacoepidemiology & Drug Safty. 1999; 8: 261-4.

68.Mackay F, Freemantle S and Mann RD. Nefazodone in community
use: the results of Prescription-Event Monitoring. Pharmacoepidemiology &
Drug Safty. 1999; 8: 267-73.

69.Dunn NR, Arscott A, Thorogood M, Thomas S, Davison H and Richardson J.
Case and Control Recruitment, and Validation of Cases, for the MICA Case-
Control Study in England, Scotland and Wales. Pharmacoepidemiology &
Drug Safty. 1999; 8: 285-90.

70.Dunn NR and Mann RD. Prescription-event and other forms of epidemiological
monitoring of side-effects in the UK. Clinical and Experimental Allergy.
1999; 29: Supplement 3: 217-39.

71.Mann RD, Mackey F, Pearce G, Freemantle S and Wilton LV. Losartan; a study
of pharmacovigilance data on 14 522 patients. Journal of Human Hypertension.
1999; 13: 551-7.

72.Dunn NR, Freemantle S and Mann RD. Cohort study on calcium channel
blockers, other cardiovascular agents, and the prevalence of depression. Br J
Clin Pharmacol. 1999; 48: 230-3.

73.Mackay F, Wilton L and Mann R. Setting up Prescription-Event Monitoring for
National Postmarketing Surveillance-Problems and Potential. Ed: Hugh
McGavock In: Handbook of Drug Reserch Methodology 1^st Edition, 2000.
1999; Chapter 19, 275-89.

74.Dunn N, Wilton LV, Shakir. Letter: Stevens-Johnson syndrome and
antiepileptics. The Lancet. 1999; 354: 1033.

75.Dunn N, Faragher B, Thorogood M, deCaestecker L, MacDonald T, McCollum
C, Thomas S and Mann RD. Risk of myocardial infarction in young female
smokers. Heart. 1999; 82: 581-3.

76.Wilton LV, Stephens MDB and Mann RD. Visual field defects associated with
vigabatrin. BMJ. 1999; 319: No 7218, 1165-6.

77.Martin R, Rink E, Wilkinson D and Mann RD. Did knowledge, opinions,
background and health authority advice influence early precribing of the novel
Alzheimer's disease drug donepezil in general practice?: national postal survey.
Pharmacoepidemiology & Drug Safty. 1999; 8: 413-22.

78.Mackay FJ, Dunn NR and Mann RD. Antidepressants and the serotonin
syndrome in general pratice. Br J Gen Pract. 1999; 49: 871-4.

79.Mackay FJ, Dunn NR Martin RM, Pearce GL, Freemantle SL and Mann RD.
Newer antidepressants: a comparison of tolerability in general practice. Br J
Gen Pract. 1999; 49: 892-6.

80.Mann RD, Biswas P, Freemantle S, Pearce G and Wilton L.
The pharmacovigilance of tamsulosin: event data on 12484 patients. BJU
International. 2000; 85: 446-50.

81.Dunn NR, Arscott A, Thorogood M, Faragher B, deCaestecker L, MacDonald T,
McCollum C, Thomas S and Mann RD. Regional variation in incidence and case
fatality of myocardial infraction among young women in England,Scotland and Wales.
J Epidemiol Community Health. 2000; 54: 293-8.

82.Shakir S and Wilton L. Drug Safety Research Unit and pharmacoepidemiology.
International Journal of Pharmaceutical Medicine.2000; 14(1): 1-2.

83.Mann RD, Pearce GL, Dunn N, Shakir S. Sedation with "non-sedating"
antihistamines: four prescription-event monitoring studies in general practice.
BMJ. 2000; 320: 1184-86.

83' comment on paper 83
R E Ferner. Commentary:Reporting of adverse events is worth the effort.
BMJ. 2000; 320: 1186-87.

84. Mann RD. Risk factor for ischaemic heart disease in young women.
Women's Health Update: 1-3

85. Martin RM, Biswas P and Mann RD. The incidence of adverse events and risk
factors for upper gastrointestinal disorders associated with meloxicam use amongst
19087 patients in general practice in England: cohort study. Br J Clin Pharmacol. 2000;
50(1) : 35-42.

86. Craig McFeely PM , Freemantle SL, Pearce GL and Shakir S. QT lengthening and
life-threatening arrhythmias associated with fexofenadine. Br J Gen Pract. 2000; 50(451) :148.

87. Dunn NR, Pearce GL and Shakir S. Association between SSRIs and upper gastrointestinal
bleeding. SSRIs are no more likely than other drugs to cause such bleedeing. BMJ Letters.2000;
320:1405-6.

88. Mann RD. Prescription-event Monitoring. In: Pharmacoepidemiology, Third Edition. Ed:BL Stom.
John & Sons Ltd. UK. 2000;231-46

89. Dunn NR. Arscott A and Mann RD. Costs of seeking ethics approval before and after the
introduction of multicentre research ethics committees. JR Soc Med.2000:93;511-2.

90. Martin RM, Dunn NR, Freemantle SL and Shakir S.The rates of common adverse events
reported during treatment with proton pump inhibitors used in general practice in England:
cohort sutedies. Br J Clin Pharmacol. 2000; 50: 366-72.

91. Shakir S and Pearce GL. Prescription-event Monitoring. Prescriber. 2000;11:67-73.

92. Dunn NR, Pearce GL and Shakir S.Adverse effects associated with the use of donepezil
in general practice in England. J Psychopharmacology. 2000;14:406-8.

93. Arscott A, Nettelfield P. Myocardial infarction and oral contraceptives. Professional News.
2001;16(5): 1117-20.