2013 immp summary booklet - new zealand pharmacovigilance

The New Zealand

Intensive Medicines Monitoring Programme

A summary

Dr Mira Harrison-Woolrych, Director August 2013

Table of Contents

Section 1: Background ............................................................................................................................. 1

1.1 Introduction ....................................................................................................... 1

1.2 The importance of post-marketing surveillance .............................................. 1

1.3 Post-marketing surveillance in New Zealand ................................................... 2

Section 2: Methods and Functions of the IMMP .......................................................................... 4

2.1 Methods used by the IMMP ............................................................................... 4

2.2 Pharmacovigilance functions ............................................................................ 5

2.3 IMMP data collected/analyses performed ........................................................ 7

2.4 Privacy issues, ethics approval and patient consent ........................................ 9

2.5 Funding of the IMMP ....................................................................................... 10

Section 3: IMMP Results and other Outputs ................................................................................ 11

3.1 Signal generation ............................................................................................. 12

3.2 International publications ............................................................................... 13

3.3 Reporting results to prescribers ...................................................................... 15

3.4 Regulatory and international outcomes ......................................................... 15

Section 4: Support for the IMMP ....................................................................................................... 16

4.1 National support in New Zealand ................................................................... 16

4.2 International support for the IMMP ................................................................ 16

Section 5: New developments ............................................................................................................ 18

5.1 Enhancing existing methods ........................................................................... 18

Annex 1. IMMP Publications to August 2013

Annex 2. Letters of support for IMMP

Annex 3. Patient information leaflet

IMMP: a summary (August 2013) page 1

Section 1: Background

1.1 Introduction

The IMMP was established in 1977 as the first Prescription Event Monitoring (PEM)

programme in the world. During the 1970s, the NZ Ministry of Health and its advisory

committees became aware of the limitations of spontaneous reporting (‘yellow card schemes’)

for detecting and quantifying adverse reactions to medicines and this was a key reason for

establishing the IMMP. The early awareness in NZ of the need for additional intensive

methods in pharmacovigilance was ahead of its time: subsequent international guidelines on

pharmacovigilance planning have recommended methods which the IMMP has been using for

many years.

During its 36 year history the IMMP has monitored numerous medicines and the results of

these studies have provided an important contribution to public health and patient safety in

NZ and across the world. This contribution is reflected in the extensive IMMP publication

list of over 130 research papers (as detailed in Annex 1) and in the other outputs summarised

in Section 3 of this booklet. The IMMP has received a very high level of support from health

professionals in New Zealand and is also internationally recognised as a leading

pharmacovigilance programme. The purpose of this booklet is to summarise the methods,

functions and outputs of the IMMP; to outline the support the programme receives and to

highlight new developments.

1.2 The importance of post-marketing surveillance

Post-marketing safety studies of new medicines are required because at the time of licensing

there are inadequate safety data available for most products. Pre-marketing data are

insufficient in terms of number of patients studied (often only a few hundred individuals), the

characteristics of patients included in the trials (most studies have many exclusion criteria),

the time over which patients are studied (usually just a few weeks) and the general conditions

under which the clinical trials were performed. It is therefore extremely important to actively

monitor new medicines after they are marketed and used by patients in ‘real-life’ conditions.


Older medicines may also require post-marketing studies if utilisation changes – for example,

if a medicine becomes licensed for a new indication and exposes a significant new population.

Examples include if an older medicine becomes licensed for use in children, or if a medicine

first licensed as an anti-depressant later becomes licensed for another purpose. Another

important reason for proactively monitoring older medicines is to gain further information on

known safety issues. For example, a particular adverse reaction may have been identified in

the early years of marketing, but the occurence rate (number of patients affected per 1,000

treated) is not known and more detail on risk factors for the adverse reaction is needed.

Gaining this information from intensive monitoring studies helps doctors, pharmacists and

other health professionals advise patients about the safe use of medicines.

1.3 Post-marketing surveillance in New Zealand

The IMMP has been an integral part of post-marketing surveillance in New Zealand.

It operates within the New Zealand Pharmacovigilance Centre (NZPhvC) which is located in

the University of Otago in the Department of Preventive and Social Medicine. The IMMP is

one of the key programmes that operate within the national pharmacovigilance centre (see

Figure 1). The symbiotic relationship between the IMMP and the national spontaneous

reporting programme/Centre for Adverse Reactions Monitoring (CARM) is a key reason why

NZ has been a world leader in pharmacovigilance.

The NZPhvC works under a service provision contract funded by Medsafe - the regulatory

authority in the NZ Ministry of Health. For some years Medsafe and its advisory committees

recommended new medicines to be monitored by the IMMP and funded some (but not all)

IMMP studies. However, in recent years Medsafe support of the IMMP has decreased and at

the time of writing, although the IMMP remains within the NZ Pharmacovigilance Centre, it

will have insufficient funds to operate after December 2013.


Figure 1. The Structure of Pharmacovigilance in New Zealand 2012*

Ministry of Health

Medsafe

Medicines Adverse Reactions Committee

(MARC)

Medicines Assessment Advisory Committee

(MAAC)

New Zealand Pharmacovigilance Centre

CARM

IMMP

MERP

* After June 2012 neither the IMMP nor the MERP worked under contract to MedSafe

Notes on Figure 1

1. CARM = Centre for Adverse Reactions Monitoring

2. IMMP = Intensive Medicines Monitoring Programme

3. MERP = Medication Error Reporting Programme


Section 2: Methods and Functions of the IMMP

The main aim of the IMMP is to perform proactive and intensive surveillance of specific

medicines to study their safety and utilisation in a New Zealand population.

2.1 Methods used by the IMMP

The IMMP performs prospective observational cohort studies on selected medicines.

The method applied is known as Prescription Event Monitoring (PEM) and the use of this in

the IMMP has been fully described in the international textbook Pharmacovigilance

(Eds: Mann & Andrews; second edition 2007, Wiley & Sons, England).

In brief, the IMMP receives a record of all dispensed prescriptions for monitored medicines

from pharmacies throughout NZ and this forms the cohort of patients to be studied. Once the

cohort for each medicine has been established, follow-up questionnaires are sent to patients’

doctors (usually their GP) to obtain information about all clinical events since the medicine

was prescribed. Additional information about serious adverse events is obtained from linkage

to national datasets and other events may be identified through spontaneous reports sent to the

NZPhvC. Assessors at the IMMP determine if the clinical events are likely to be causally

related to the medicine studied or not. In this way previously unidentified side effects to

medicines are identified.

This simple but proactive methodology enables identification and assessment of particular

problems related to utilisation and safety of the monitored medicines in the NZ population.

In addition, the design of the IMMP studies allows for specific assessment of safety in

vulnerable populations (e.g. children, pregnant women, the elderly) and allows study of other

issues including withdrawal effects, drug interactions and fatal adverse events.


2.2 Pharmacovigilance functions

The IMMP performs several important functions in the NZ pharmacovigilance system and

these can be summarised as follows.

Intensified spontaneous reporting

The placement of a new medicine on the IMMP increases prescribers’ awareness and

stimulates reporting. Spontaneous reports may be received on yellow cards, electronically

via the NZPhvC website, or by fax, email or telephone. In NZ anyone - including patients

and carers - may submit an adverse reaction report to the national centre. A clinical

assessor undertakes immediate appraisal of each spontaneous report (including searches

for extra data and published literature on the issue) and an individual response is then sent

to each reporter.

Identification of new safety signals

The intensive methods used by the IMMP to identify adverse events (see Section 2.1

above) may result in identification of previously unrecognised adverse events known as

safety ‘signals’. The IMMP has identified many new signals for the monitored medicines

and these are summarised in Section 3 below.

Quantification of occurrence rates of adverse reactions

A significant advantage of the IMMP method of post-marketing surveillance is that it

enables calculation of the occurrence rates of adverse reactions, because the patient

population is accurately defined from the pharmacy dispensing data. (A recognised

limitation of spontaneous reporting is that the population exposed to the medicine is not

known and thus is it not possible to calculate how often an adverse reaction might occur).

Utilisation studies

Collection of nationwide dispensing data allows analysis of how the monitored medicines

are used in the NZ setting. Many types of utilisation study may be performed and

examples of the data collected for such studies are given in Section 2.3 below.


Specific studies of clinical issues

The IMMP has completed many specific studies of important clinical issues.

Examples of these are shown in the box below.

Risk Communication

An important function of the IMMP is to inform and educate others about the methods of

monitoring medicines and the results of IMMP studies. We aim to appropriately

communicate risks associated with medicines and use several different methods including:

Regular IMMP updates sent to pharmacists and doctors in NZ

An IMMP Patient Information Leaflet (see Annex 3)

Articles in local professional publications (e.g. New Zealand Doctor, Pharmacy

Today)

Telephone, email and fax communication with local health professionals and patients

Research publications in international journals

Conference presentations

Development of the IMMP website

Key IMMP studies of specific clinical issues

Safety and use of antipsychotic medicines in children and adolescents

(prospective cohort study)

Serious and life threatening gastrointestinal dysmotility in patients taking

clozapine (case series study)

Use of the levonorgestrel intra-uterine device in adolescent women

(cohort study)

Bed-wetting in adult patients taking antipsychotic medicines

(comparative cohort study)

Cardiovascular events in patients taking the smoking cessation medicine

varenicline (case series study)


2.3 IMMP data collected/analyses performed

In performing the monitoring studies, the IMMP collects much valuable information on

patients dispensed the monitored medicines and their subsequent clinical outcomes. It should

be noted that whilst the IMMP has the authority to collect the identifiable patient information

essential for performing accurate cohort studies, strict confidentiality practices are followed

(see Section 2.4 below) and no individual patient or reporter information is published in a way

that would allow any person in an IMMP study to be identified.

For the purpose of the monitoring studies, the following is a summary of the data collected:

Cohort characteristics/demographics

Patient age and sex

Patient ethnicity (as recorded in NZHIS records)

Geographic distribution of patients (by patient address)

Geographic distribution of dispensing pharmacies

Geographic distribution of prescribers/clinics/health centres

Utilisation data

Dispensing patterns by area and by time (e.g. new patients per month)

Details of different pack sizes and/or formulations dispensed

Total patient exposure in person-years treatment

Patterns of treatment analyses e.g. duration of treatment courses dispensed;

number of treatment courses

Reasons for stopping medicine (usually performed for patients for whom a

follow-up questionnaire has been returned)

Other utilisation analyses specific to the monitored medicine

Effectiveness assessments Whilst the primary outcome of most IMMP studies is safety, for some medicines

(e.g. varenicline for smoking cessation) it may be possible for the IMMP to obtain

information on the effectiveness of this treatment in ‘real-life’ post-marketing use.


Exposure during pregnancy IMMP studies usually include a specific questionnaire relating to exposure during pregnancy

and lactation in woman of reproductive age in the IMMP cohort. Analyses may then be

performed to determine rates of pregnancy/lactation exposure for a specific medicine cohort

and the maternal and fetal outcomes of these exposures.

Adverse events data The IMMP aims to identify all new clinical events occurring in patients after starting the

monitored medicine. These clinical events are identified using the intensive methods

described above and each adverse event undergoes causality assessment by IMMP clinical

assessors.

Summary data on adverse events include:

Summary listings of all adverse events identified

Details of serious adverse event reports

Adverse event analysis by System Organ Class

Adverse event analysis by patient (individual patients may have multiple adverse event)

Specific analyses of clinically related events (e.g. psychiatric events)

Specific analyses in population sub-groups (e.g. children, elderly)

Reports of death and mortality analyses Deaths of patients who were dispensed a monitored medicine are identified from follow-up

questionnaires, spontaneous reports and also by record linkage of the IMMP cohort to the

NZHIS national mortality datasets. Once a death has been identified, supplementary follow-

up information is obtained (from doctors, coroners and pathologists if necessary) to confirm

the cause of death and other relevant clinical details.


2.4 Privacy issues, ethics approval and patient consent

The processes and practices of the IMMP have been set up to comply with the NZ Health

Information Privacy Code 1994 and the Privacy Commissioner has been advised of the

purpose and methodology of the programme. In line with the Privacy Code, there are

processes in place within the IMMP to protect patient privacy and maintain confidentiality.

These include appointment of a privacy officer, training of staff in all aspects of

confidentiality (formalised in a confidentiality agreement signed by IMMP staff) and strict

processes regarding collection, storage and publication of patient data.

The ethical aspects of the IMMP have been formally reviewed and Ethics Committee

approval has been granted for the ongoing work of the programme (Ethics Reference:

OTA/04/32/CPD). Therefore Ethics Committee approval is not required for routine new

monitoring studies. For additional studies that are not part of the routine monitoring, ethics

approval is sought in the usual way and approval has invariably been given.

Regarding patient consent for involvement in the programme, the IMMP operates on the

‘opt-out’ principle, like other national epidemiological studies. Patients should be informed

by their doctor that they have been prescribed a monitored medicine, the reasons why their

medicine is monitored and the type of information collected. The IMMP provides

information leaflets that doctors o r p h a r m a c i s t s may give to patients (see Annex 3).

The patient has the right to opt out of the monitoring study by requesting that the IMMP

does not store their personal data.


2.5 Funding of the IMMP

During its 36 year history the IMMP has received funding from multiple sources including the

NZ Ministry of Health (Medsafe), research grants and unconditional donations from

pharmaceutical companies and other sources. The IMMP has operated using a mixed funding

model in which more than one funding source may support a particular study. Funding bodies

have had no role in the design, conduct, analysis or decision to publish any IMMP study and

funding sources are always stated in IMMP publications. In taking these steps we have

always sought to minimise any potential conflicts of interest in IMMP studies.

The IMMP does not pay pharmacists or doctors for any of the data or other information

submitted, or for their time in sending it to us. Participation in the programme is considered

to be in line with professional codes of conduct in the interest of protecting patient safety.

This contribution is recognised and acknowledged whenever possible, including an agreement

with the Royal NZ College of General Practitioners that Maintenance of Professional

Standards Points (MOPS) may be awarded for completion of IMMP questionnaires.


Section 3: IMMP Results and other Outputs

The IMMP has completed intensive monitoring studies on numerous medicines and groups of

medicines including:

Class of medicines Monitored medicines Period of study

Patients in IMMP cohorts

Smoking cessation medication Varenicline 2007-2012 20,000+

Atypical antipsychotic medicines Olanzapine Quetiapine Clozapine Risperidone

1999-2007 25,000+

Anti-obesity medication Sibutramine 2001-2006 15,000+

Intra-uterine devices Multiload Cu375 Mirena LNG

1988-2005 25,000+

COX II inhibitors Celecoxib Rofecoxib Etoricoxib Parecoxib Valdecoxib

2000-2004 75,000+

Antidepressants Mianserin Fluoxetine Moclobemide Nefazodone

1983-2002 40,000+

Asthma medicines Salmeterol Eformoterol

1992-2000 10,000+

ACE inhibitors Captopril Enalapril Lisinopril

1981-1991 50,000+

Results from these studies have been published in national and international publications

(see Annex 1) and were also presented to Medsafe at regular intervals. Other IMMP outputs

include reports which are shared with international pharmacovigilance bodies and several

other methods of risk communication (see Section 2.2 above). In addition to the more formal

outputs, the IMMP also provides ongoing advice and feedback to prescribers, health

professionals, industry and patients. This occurs regularly through personal communication

with IMMP staff in letters, telephone calls, emails, meetings and collaborative projects.


3.1 Signal generation

The IMMP has successfully identified a number of signals (previously unidentified adverse

reactions to medicines) which have been reported to the Ministry’s advisory committees, have

been published in the international literature and have also resulted in regulatory action. An

early analysis of IMMP signals was summarized in Pharmacovigilance 2002 (Mann &

Andrews (eds), Wiley & Sons, England). In brief, this analysis showed that during a ten year

period, 153 signals were reported to the Medicines Adverse Reactions Committee and of

these, 132 (86%) were notified prior to any publication found in the international literature.

Eighty-six (56%) of these signals were subsequently strengthened or confirmed by at least one

non-IMMP publication.

Monitoring of IMMP medicines has continued to generate new signals including:

Medicine New signal Outcome

Varenicline Memory impairment reported to Medsafe, 2012; published in Eur J Clin Pharmacol, 2013

Varenicline Epistaxis (nose bleeds) and other haemorrhagic events

published in Eur J Clin Pharmacol, 2012

Varenicline Withdrawal reactions published in Prescriber Update, 2009 and Drug Safety, 2011

Antipsychotic medicines Symptoms of depression in children published in Drug Safety, 2007

Mirena LNG IUD Alopecia (hair loss) published in Contraception, 2007

Quetiapine Alopecia (hair loss) published in Int J Clin Psychopharm, 2007

Sibutramine QT prolongation published in Br J Clin Pharm, 2006

COX II inhibitors Dysrhythmias published in Drug Safety, 2005

Risperidone Epistaxis (nose bleeding) published in BMJ, 2004

Sibutramine Memory impairment published in BMJ, 2004

Nefazodone Hepatotoxicity reported to Medsafe, 2000 (NZ first in world to take action.)


3.2 International Publications

The IMMP regularly publishes research articles (in recent years approximately four per year)

and over 130 of these are listed in Annex 1. Some of these publications have been key papers

including:

Cough associated with ACE inhibitors

The signal of cough associated with captopril and enalapril was published in the British

Medical Journal in 1987. This was the first full account and remains the definitive

description of this important adverse reaction to ACE inhibitors, which is now well

recognized.

Agranulocytosis with mianserin

This issue was published in the Lancet and led to withdrawal of funding of this medicine

in NZ. In the UK, the Medicines Control Agency used these data to support regulatory

action in a court case against the manufacturer.

Intrauterine device (IUD) cohort studies

IMMP cohort studies of the copper IUD Multiload Cu 375 have been published in

international journals. A large study of IUD insertion gave reassuring results regarding a

low incidence of complications of insertion. The second study concerned perforation of

the uterus with IUD insertion and reported results from 10 years follow-up of women

using Multiload Cu 375. The results of this study were cited in the UK Faculty of Family

Planning Guidance on copper IUDs (Journal of Family Planning 2004: 30 (1)).

Visual disturbance with the COX II inhibitors

This paper was published in the BMJ in 2003 and a review of this problem was

subsequently commissioned by Expert Opinion on Drug Safety.

Safety and usage of atypical antipsychotic medicines in children

This nationwide cohort study was published in Drug Safety in 2007. The study was

conducted because of increasing use of these medicines in children and was the first NZ

study to describe the utilisation and safety of antipsychotic medicines in this population.


Clozapine and gastrointestinal dysmotility

In collaboration with other researchers, the IMMP published this extensive case series

study about a potentially fatal (but under-recognised) adverse effect of clozapine.

The report included clinical recommendations for prevention and management of these

problems.

Nocturnal enuresis in adult patients taking atypical antipsychotic medicines

This paper reported a detailed IMMP cohort study which compared the risk of bedwetting

in adult patients taking clozapine with patients taking other antipsychotic medicines.

The study showed that about one in five patients taking clozapine experienced this adverse

effect. The paper was published in 2011 in the British Journal of Psychiatry with an

accompanying editorial.

Psychiatric adverse effects associated with varenicline

This prospective cohort study – published in Drug Safety in 2011 – quantified all

psychiatric adverse events identified and confirmed a causal relationship between

varenicline and symptoms of depression. The study also identified withdrawal symptoms

on stopping varenicline as a potential adverse effect.


3.3 Reporting results to prescribers

In addition to the international publications included in Annex 1, the IMMP regularly

communicates results to health professionals in NZ. Pharmacovigilance articles based on

IMMP studies have been published in the Ministry of Health’s Prescriber Update and in

New Zealand Doctor and Pharmacy Today magazines. The IMMP also regularly sends

information to doctors (e.g. with follow-up questionnaires), presents information at

conferences and meetings and also sends interim monitoring summaries to prescribers,

pharmacists and professional bodies. The IMMP methods of risk communication are

summarised in Section 2.2 of this booklet.

3.4 Regulatory and international outcomes

IMMP studies have resulted in regulatory action in New Zealand including:

data sheet changes (addition/strengthening of warnings etc.)

requests to marketing authorisation holders for further analysis or information

communications to health professionals

withdrawal of products from the market

IMMP data and reports have also been shared with other regulatory authorities – for example

the Therapeutic Goods Administration (TGA) in Australia, the Medicines and Healthcare

products Regulatory Authority (MHRA) in the UK and the European Medicines Agency

(EMA).

IMMP results have also been shared with the Institute for Safe Medication Practices (ISMP)

in Canada/USA, the World Health Organisation (WHO) Adverse Drug Reaction monitoring

groups and with the International Society of Pharmacovigilance (ISoP). This global

collaboration is extremely important in international pharmacovigilance.


Section 4: Support for the IMMP

4.1 National support in New Zealand

The IMMP receives considerable support from health professionals in New Zealand.

Dispensing data returns from pharmacies have been maintained at over 95% for many years

and response rates to follow-up questionnaires sent to doctors have been above 80% for some

studies. Requests for further information from GPs, specialists and coroners are most often

met with a willingness to assist the IMMP in monitoring patient safety in NZ.

4.2 International support for the IMMP

International experts in pharmacoepidemiology have referred to the IMMP as world-leading

programme with many advantages over other systems (Balkrishnan & Furber Developing an

optimal approach to global drug safety. Journal of Internal Medicine 2001; 250: 271-279).

The programme has the support of many experts in pharmacovigilance and

pharmacoepidemiology. In response to threats of closure of the IMMP during 2004, many

prominent individuals wrote to the Director General of Health and/or the Minister for Health

requesting that this decision was reconsidered. These responses included supporting letters

sent on behalf of the International Society of Pharmacoepidemiology (ISPE) and the

International Society for Pharmacovigilance (ISOP). In July 2004, the British Medical

Journal published an open letter to the NZ Minister of Health which expressed concern at the

potential threat to the IMMP. This letter was signed by 35 leading pharmacoepidemiologists

from around the world. A copy of this letter is included on page 17.

In 2012 when Medsafe stopped funding the IMMP, international experts representing several

different pharmacovigilance bodies wrote to the NZ Health Quality and Safety Commission

requesting this new government body support and fund the IMMP. Copies of these letters of

support are included at Annex 2. Unfortunately, this action did not result in any new funding

from the Ministry of Health.


Section 5: New developments

The IMMP is always seeking to improve and update its methods in order to perform the

monitoring studies more efficiently and to the highest possible standard.

5.1 Enhancing existing methods

In recent years the methods used by the IMMP have been enhanced in the following ways:

Data Linkage Studies

Linkage with the NZ Health Information Services (NZHIS) databases is routinely

undertaken in most IMMP studies. The purpose of this is to identify serious, life-

threatening and fatal adverse events associated with the monitored medicines.

Specific studies of clinical issues

In addition to the routine monitoring, the IMMP has conducted several specific studies in

order to investigate particular clinical issues. These have included both utilisation and

safety studies and examples of these are given in Sections 2.2 and 3.2 of this booklet.

Patient reporting

The IMMP has piloted new methods to invite patient reporting on a monitored medicine

(dapoxetine). This included asking pharmacists to hand out flyers with details of how to

report directly to the IMMP and asking doctors to give each patient a follow-up

questionnaire to complete. Patients were also invited to use an electronic reporting form

on the IMMP website.

Electronic dispensing data collection (eIMMP)

The IMMP investigated the feasibility of electronic transmission of prescription

dispensing data directly to the IMMP and gained strong support from pharmacists for this.

The ‘eIMMP’ system was subsequently developed in collaboration with the pharmacy

software providers, and at the time of writing 78% of community pharmacies transmit

IMMP dispensings electronically and automatically each month. Electronic capture of

dispensing data has significantly increased the speed with which patient cohorts can be

established for IMMP studies.

IMMP: a summary (August 2013) Annex 1, page 1

Annex 1. IMMP Publications to August 2013

2013

Harrison-Woolrych M, Paterson H, Tan M. (2013). Exposure to the smoking cessation medicine varenicline during pregnancy: a prospective nationwide cohort study. Pharmacoepidemiol Drug Saf. Aug 8. doi: 10.1002/pds.3489. [Epub ahead of print]

Tan M and Harrison-Woolrych ML (2013). Memory impairment associated with varenicline: a case series from the New Zealand Intensive Medicines Monitoring Programme. Eur J Clin Pharmacol 69(5):1195-1196.

2012

Harrison-Woolrych ML (2012). Varenicline for smoking cessation. [Editorial]. BMJ 345: e7547.

Bahri P and Harrison-Woolrych ML (2012). How to improve communication for safe use of medicines? Discussions on social marketing and patient-tailored approaches at the Annual Meetings of the WHO Programme for International Drug Monitoring. Drug Safety 35(12): 1073-1097.

Bahri P and Harrison-Woolrych ML (2012). Focussing on risk communication about medicines: why now? Drug Safety 35(11): 971-975.

Harrison-Woolrych M, Harmark L, Tan M, Maggo S and van Grootheest K (2012). Epistaxis and other haemorrhagic events associated with the smoking cessation medicine varenicline: a case series from two national pharmacovigilance centres. Eur J Clin Pharmacol 68: 1065-72

Harrison-Woolrych M, Maggo S, Tan M, Savage R and Ashton J (2012). Cardiovascular events in patients taking varenicline: a case series from intensive post-marketing surveillance in New Zealand. Drug Safety 35 (1): 1-11

2011

Harrison-Woolrych M (2011) Patient reporting encouraged during monitoring of dapoxetine in New Zealand (letter). Drug Safety 34 (11): 1115-6

Harrison-Woolrych M and Ashton J (2011). Psychiatric adverse events associated with varenicline: an intensive post marketing prospective cohort study in New Zealand. Drug Safety 34 (9): 1-10

Harrison-Woolrych ML, Skegg K, Ashton J, Herbison P and Skegg DCG (2011). Nocturnal enuresis in adults taking clozapine, risperidone, olanzapine and quetiapine: a comparative cohort study. British Journal of Psychiatry 199: 140-144

Van Grootheest AC, Sachs B, Harrison-Woolrych M, Caduff-Janosa P and van Puijenbroek E (2011). Uterine perforation with the levonorgestrel releasing intrauterine device: analysis of reports from four national Pharmacovigilance Centres. Drug Safety 34 (1):83-88


Harrison-Woolrych M, Jamieson S, Malik M, Holt A and Herbison P (2011). Electronic data capture of dispensing data by the New Zealand Intensive Medicines Monitoring Programme: a consultation study of community and hospital pharmacists. International Journal of Pharmacy Practice 19 (2): 136-139

2010

Harrison-Woolrych ML (2010). Varenicline and suicide: Safety data from New Zealand. British Medical Journal 339:b5654

Harrison-Woolrych M, Ashton J and Herbison P (2010). Fatal and non-fatal cardiovascular events in a general population prescribed sibutramine in New Zealand: a prospective cohort study. Drug Safety 33 (7):605-613

Harrison-Woolrych M and Ashton J (2010). Utilisation of the smoking cessation medicine varenicline: an intensive post-marketing study in New Zealand. Pharmacoepidemiology and Drug Safety 19: 1-5

Harrison-Woolrych M (2010). The use of varenicline (Champix) in NZ: key findings from IMMP study. Prescriber Update 31(3):22 Available at: www.medsafe.govt.nz/profs/PUArticles/TheUseOfVareniclineSept10.htm

2009

Harrison-Woolrych ML. (2009) Varenicline and suicide; Safety data from New Zealand. BMJ 339: b5654

Paterson H, Ashton J and Harrison-Woolrych ML (2009). A nationwide cohort study of the use of the levonorgestrel intrauterine device in New Zealand adolescents. Contraception 79(6): 433-438

Harrison-Woolrych ML. (2009). Psychiatric reactions with varenicline: interim results from intensive monitoring in New Zealand. Prescriber Update 30(2): 9

2008

Kunac DL, Harrison-Woolrych ML and Tatley MV (2008). Pharmacovigilance in New Zealand: The role of the New Zealand Pharmacovigilance Centre in facilitating safer medicines use. NZ Medical Journal 121(1281): 76-89 (available at: www.nzma.org.nz/journal/121-1283/3286)

Hill GR and Harrison-Woolrych ML (2008). Clozapine and myocarditis: a case series from the New Zealand Intensive Medicines Monitoring Programme. NZ Medical Journal 121(1281): 68-74 (available at: www.nzma.org.nz/journal/121-1281/3288)

Palmer SE, McLean RM, Ellis PM and Harrison-Woolrych ML (2008). Life-threatening clozapine-induced gastro-intestinal hypomotility: an analysis of 102 cases. Journal of Clinical Psychiatry 69(5): 759-68

Clark DWJ, Ashton JA, Wallace AK, Zhou L, Kennedy MA (2008). Pharmacogenetic investigation using a pharmacovigilance database. PharmacoVigilance Review 2: 9-13


2007

Harrison-Woolrych ML & Coulter DM (2006). PEM in New Zealand. In: Pharmacovigilance (second edition). Mann R & Andrews E (editors) pp 317-322 John Wiley and Sons Chichester, England 2007.

McLean R & Harrison-Woolrych ML (2006). Alopecia associated with quetiapine. International Clinical Psychopharmacology 22(2):117-119

Paterson H, Clifton J, Miller D, Ashton J and Harrison-Woolrych ML. (2007). Hair loss with use of the levonorgestrel intrauterine device. Contraception 76(4):306-9

Hill G, Ashton J and Harrison-Woolrych ML. (2007). Sibutramine usage in New Zealand: an analysis of prescription data by the Intensive Medicines Monitoring Programme. Pharmacoepidemiology and Drug Safety 16:1217-1226

Harrison-Woolrych ML, Garcia-Quiroga J, Ashton J and Herbison P. (2007). Safety and usage of atypical antipsychotic medicines in children: a nationwide prospective cohort study. Drug Safety 30(7):569-579

Ellis PM, McLean RM and Harrison-Woolrych ML. (2007). Clozapine: Fatal constipation more common than fatal agranulocytosis. Prescriber Update 28(1):7

2006

Coulter DM, Clark DW, Zhou L, Ashton J and Harrison-Woolrych ML (2006). Safety monitoring of celecoxib and rofecoxib in the New Zealand IMMP. In: Trends in COX-2 inhibitor research. (Ed MJ Howardell) pp105-135 Nova Science Publishers Inc. New York 2006.

Harrison-Woolrych ML, Garcia-Quiroga J, Ashton J & Herbison P. (2006). Safety and usage of atypical antipsychotic medicines in children: a post-marketing prospective cohort study in New Zealand. Drug Safety 29(10): 986 (abstract from ISoP 2006).

Clark DWJ and Harrison-Woolrych ML (2006). The role of the New Zealand Intensive Medicines Monitoring Programme in identification of previously unrecognised signals of adverse drug reactions. Current Drug Safety 1(2):169-178

Harrison-Woolrych ML, Clark DWJ, Hill GR, Rees MI & Skinner JR. (2006). QT interval prolongation associated with sibutramine. British Journal of Clinical Pharmacology 61(4);464-9

Harrison-Woolrych ML, Hill GR & Clark DWJ. (2006). Bruising associated with sibutramine: results from postmarketing surveillance in New Zealand. International Journal of Obesity 30: 1315-17


2005

Savage R. Cyclo-oxygenase-2 inhibitors: when should they be used in the elderly? (2005). Drugs Aging 22(3):185-200

Harrison-Woolrych ML, Herbison P, McLean R, Ashton J and Slattery J. (2005). Incidence of thrombotic cardiovascular events in patients taking celecoxib compared with those taking rofecoxib: interim results from the New Zealand Intensive medicines Monitoring Programme. Drug Safety 28(5):435-442

2004

Clark DWJ, Donnelly E, Coulter DM, Roberts RL, Kennedy MA (2004). Linking pharmacovigilance with pharmacogenetics. Drug Safety 7(15): 1171-1184

Coulter DM and Clark DWJ (2004). Disturbance of vision by cylco-oxygenase-2 inhibitors. Expert Opinion on Drug Safety 3(6): 607-614

Clark DW and Harrison-Woolrych ML (2004). Sibutramine may be associated with memory impairment. British Medical Journal 329: 1316

Coulter DM and Clark DWJ. Visual disturbances with COX-2 inhibitors. (2004). Prescriber Update 25(1): 8-9.

Harrison-Woolrych ML and Clark DWJ. (2004). Nose bleeds associated with use of risperidone. BMJ 328: 1416.

Clark DWJ; Layton D and Shakir SAW. (2004). Do some inhibitors of cyclooxygenase-2 (COX-2) increase the risk of thromboembolic events? Linking pharmacology with pharmacoepidemiology. Drug Safety 27(7): 427-456

2003

Coulter DM, Clark DWJ, Savage RL. (2003). Celecoxib, rofecoxib and acute temporary visual impairment. BMJ 327: 1214-5

Clark DWJ, Coulter DM. (2003). Psoriasis associated with rofecoxib. Arch Dermatol 139:1223

Coulter DM, Passier JLM, Clark DWJ, van Puijenbroek EP. (2003). Activation of pain by sumatriptan. Headache 43:994-8

Harrison-Woolrych M, Zhou L, Coulter D. (2003). Insertion of intrauterine devices: a comparison of experience with Mirena and Multiload Cu375 during post-marketing monitoring in New Zealand. NZ Med J 116:1179

Zhou L, Harrison-Woolrych M, Coulter D. (2003). Use of the NZ IMMP to study the levonorgestrel releasing device (Mirena). Pharmacoepidemiology and Drug Safety 12:371-77

Harrison-Woolrych M, Ashton J, Coulter D. (2003). Uterine perforation on intrauterine device insertion: is the incidence higher than previously reported? Contraception 67:53-6


2002

Harrison-Woolrych M, Ashton J, Coulter D. (2002). Insertion of the Multiload Cu375 intrauterine device: experience in over 16,000 New Zealand women. Contraception 66:387-91

Coulter DM. (2002). The development of Prescription Event Monitoring in the New Zealand Intensive Medicines Monitoring Programme. In: Mann R and Andrews, editors. Pharmacovigilance. Chichester: John Wiley & Sons Ltd. p. 345-62

Coulter DM. (2002). Signal generation in the New Zealand Intensive Medicines Monitoring Programme: a combined clinical and statistical approach. Drug Safety 25(6):433-9

2001

Intensive Medicines Monitoring Programme [editorial]. (2001). Interactions 48

Coulter DM. (2001). Privacy issues and the monitoring of sumatriptan in the New Zealand Intensive Medicines Monitoring Programme. Pharmacoepidemiology and Drug Safety 10:1-5

Coulter DM, Bate A, Meybon RHB, Lindquist M, Edwards IR. (2001). Antipsychotic drugs and heart muscle disorder in international pharmacovigilance: data mining study. BMJ 322:1207-1209

2000

Coulter DM. (2000). The New Zealand Intensive Medicines Monitoring Programme in pro-active safety surveillance. Pharmacoepidemiology and Drug Safety 9:273-280

Clark D, Morgan A, Hananeia L, Coulter D and Olds R. (2000). Drug Metabolism Genotypes and their association with adverse reactions in selected populations: a pilot study of methodology. Pharmacoepidemiology and Drug Safety 9:393-400

1999

Clark DWJ, Coulter DM, Hananeia L, and Olds R. (1999). Genotypes of CYP2D6 and CYP2C19 in patients from the New Zealand Intensive Medicines Monitoring Programme (NZIMMP) and a control population. Proceedings of Aust Soc Clin Exp Pharmacol Toxicol (ASCEPT) 6:131

Coulter DM. (1999). Specialist only drug snags may present to GPs first. NZ Fam Physician 26(6):21-23

Coulter DM. (1999). Salmeterol and eformoterol monitoring: progress report. NZ Fam Physician 26(3):15-17

Pillans PI, Mathew TH, Coulter DM. (1999). Pharmacovigilance in Australia and New Zealand: towards 2000. Med J Aust 170:245-6


Castellsague J, Ashton J, Pethica D, Coulter DM. (1999). Mortality among users of formoterol in the New Zealand Intensive Medicines Monitoring Programme [abstract]. Am J Respiratory and Critical Care Medicine 159(3 Pt 2): A136

Beggs PW, Clark DWJ, Williams SM, Coulter DM. (1999). A comparison of the use, effectiveness and safety of bezafibrate, gemfibrozil and simvastatin in normal clinical practice using the New Zealand Intensive Medicines Monitoring Programme (IMMP). Br J Clin Pharmacol 47:99-104

1998

Coulter DM. (1998). Reactions to omeprazole obscured by aging process. NZ Fam Physician 25(3):18-20

Coulter DM. (1998). The New Zealand Intensive Medicines Monitoring Programme. Pharmacoepidemiology and Drug Safety 7:79-90

1990 - 1997

Coulter DM. (1997). Interim results of Multiload Cu375 monitoring reassuring. NZ Fam Physician 24(2): 14-16

Coulter DM. (1997). Psychiatric and behavioural responses to sumatriptan (Imigran). NZ Fam Physician 24(5):19-22

Pillans PI. (1997). National Centre for Adverse Reactions Monitoring report for the period 1 July, 1994 to 30 June 1996. NZ Med J 110:383-5

Coulter DM. (1996). Reasons for stopping drugs are monitored in New Zealand [letter]. BMJ 313:756

Pillans PI, Coulter DM, Black P. (1996). Angioedema and urticaria with angiotensin converting enzyme inhibitors. Eur J Clin Pharmacol 51:123-26

Coulter DM. (1996). Moclobemide and fluoxetine compared. NZ Fam Physician 23(6):39-40

Coulter DM. (1996). Beta2 agonists under scrutiny. NZ Fam Physician 23(4):16

Coulter DM, Pillans PI. (1995). Fluoxetine and extrapyramidal side effects. Am J Psychiatry 152:122-5

Wood R. (1995). Bronchospasm and cough as adverse reactions to the ACE inhibitors captopril, enalapril and lisinopril. A controlled retrospective cohort study. Br J Clin Pharmacol 39:265-70

Coulter DM, Pillans PI. (1995). Hypertension with moclobemide [letter]. Lancet 346:1032

Coulter DM. (1995). Intensive Medicines Monitoring Programme: Sumatriptan and possible autonomic imbalance. NZ Fam Physician 22(4):152


Coulter DM. (1995). Intensive Medicines Monitoring Programme: Monitoring of omeprazole. NZ Fam Physician 22(2):76-7

Coulter DM. (1995). Intensive Medicines Monitoring Programme: Further experience with monitoring sumatriptan (Imigran). NZ Fam Physician 22(1):31

Pillans PI and Coulter DM. (1994). Centre for Adverse Reactions Monitoring report for the year ending 30 June 1994. NZ Med J 108:488-91

Coulter DM. (1994). The Intensive Medicines Monitoring Programme and the Health Information Privacy Code. NZ Fam Physician 21(2):79

Coulter DM. (1994). Intensive Medicines Monitoring Programme: Lipid lowering agents and reasons for cessation of therapy. NZ Fam Physician 21(1):29

Pillans PI and Coulter DM. (1994). Centre for Adverse Reactions Monitoring report for the year ending 30 June, 1993. NZ Med J 107:490-3

Pillans PI and Coulter DM. (1994). Fluoxetine and hyponatraemia - a potential hazard in the elderly. NZ Med J 107:85-6

Woods DJ, Coulter DM and Pillans P. (1994). Interaction of phenytoin and fluoxetine [letter]. NZ Med J 107:19

Coulter DM. (1993). Intensive Medicines Monitoring Programme: Fluoxetine interactions. NZ Fam Physician 20(3):110

Coulter DM. (1993). Intensive Medicines Monitoring Programme: Early experience with sumatriptan. NZ Fam Physician 20(1):22

Coulter DM. (1993). Short term safety assessment of cilazapril. NZ Med J 106:497-9

Coulter DM and Pillans PI. (1993). Angiotensin-converting enzyme inhibitors and psoriasis [letter]. NZ Med J 106:392-3

Edwards IR, Coulter DM and Macintosh D. (1992). Intestinal effects of captopril. Br Med J 304:359-60

Coulter DM. (1992). Intensive Medicines Monitoring Programme: Bezafibrate, gemfibrozil and simvastatin. NZ Fam Physician 19(1):30

Coulter DM. (1992). Intensive Medicines Monitoring Programme: Early results from moclobemide. NZ Fam Physician 18(4):193

Coulter DM. (1991). Intensive Medicines Monitoring Programme: Refining the method of monitoring. NZ Fam Physician 18(2):75-6

Coulter DM and Edwards I R. (1990). Mianserin side-effects [letter]. Lancet 336:1439

Coulter DM. (1990). Mianserin and agranulocytosis [letter]. Lancet 336:1010

Coulter DM and Edwards IR. (1990). Mianserin and agranulocytosis in New Zealand. Lancet 336:785-7


Coulter DM. (1990). Intensive Medicines Monitoring Programme – A review of reactions to ACE inhibitors. NZ Fam Physician 17(3):139

Coulter DM. (1990). Intensive Medicines Monitoring Programme: ACE inhibitors and pancreatitis. NZ Fam Physician 17(2):87

Coulter DM. (1990). Intensive Medicines Monitoring Programme: Experience with aciclovir. NZ Fam Physician 17(1):31

Coulter DM, Edwards IR and Savage RL. (1990). Survey of neurological problems with amiodarone in the New Zealand Intensive Medicines Monitoring Programme. NZ Med J 98-100

1980 - 1989

Coulter DM. (1989). Intensive Medicines Monitoring Programme: Experience with fluoxetine. NZ Fam Physician 16(4):205

Coulter DM. (1989). Intensive Medicines Monitoring Programme: Hypotension and ACE inhibitors. NZ Fam Physician 16(3):144-5

Coulter DM. (1989). Intensive Medicines Monitoring Programme: Enalapril and trigeminal neuralgia. NZ Fam Physician 16(2):100

Coulter DM. (1989). Intensive Medicines Monitoring Programme: Changing to enalapril. NZ Fam Physician 16(1):17

Edwards IR and Coulter DM. (1989). ACE Inhibitors and anaemia [letter]. NZ Med J 102:325

Coulter DM. (1988). Eye pain with nifedipine and disturbance of taste with captopril: A mutually controlled study showing a method of postmarketing surveillance. Br Med J 296: 1086-8

Coulter DM and Edwards IR. (1988). Cough and angiotensin converting enzyme inhibitors [letter]. Br Med J 296:863

Coulter DM. (1988). NZ Intensive Medicines Monitoring Programme: ACE inhibitors and the internal ear. NZ Fam Physician 15(4):170

Edwards IR, Beasley MG and Coulter DM(1988). Drug Reactions. Medicines Adverse Reactions Committee: Report for the two years ending March 1987. NZ Med J 101:826-8

Edwards IR, Coulter DM, Beasley DMG and MacIntosh D. (1987). Captopril: 4 years of post marketing surveillance of all patients in New Zealand. Br J Clin Pharmacol 23:529-36

Coulter DM, Edwards IR. (1987). Cough associated with captopril and enalapril. Br Med J 294:1521-3

Edwards IR. (1987). Combined 21st & 22nd Annual Reports, April 1985-March 1987. Medicines Adverse Reactions Committee; Sep 1987

Coulter DM. (1987). Duplicate Rx pad trial boosts IMP reporting. NZ Pharmacy 7:30-1

Edwards IR. (1987). Monitoring for drug safety [letter]. Trends in Pharmacol Sciences 8:52-3


Edwards IR, Coulter DM and Beasley G. (1986). Medicines Adverse Reactions Committee: Report for the two years ending March 1985. NZ Med J 99:719-22

Edwards IR. (1986). Post-marketing surveillance in New Zealand. Medical Toxicology 1(Suppl.1); 83-5

Coulter DM. (1986). Pilot trial in the use of duplicate prescription pads for the Intensified Adverse Drug Reaction Reporting Scheme. Research Review 180-1

Coulter DM, Edwards IR and McQueen EG. (1986). Post-marketing surveillance in the general population: New Zealand. In: Inman WHW,ed. Monitoring for Drug Safety 2nd ed. Lancaster, England: MTP Press, 119-34

Coulter DM. (1985). Adverse reactions to tocainide [letter]. NZ Med J 98(782): 552-3

Edwards IR. (1985). Mianserin [letter]. NZ Med J 98:350

Edwards IR. (1985). Agranulocytosis and mianserin [letter]. NZ Med J 98:75-6

Coulter DM and Edwards IR. (1984). Amiodarone: An appraisal of the New Zealand experience. Hospital Therapeutics Jul:5-9

Edwards IR. (1984). Medicines Adverse Reactions Committee: Eighteenth annual report 1983. NZ Med J 97:729-32

McQueen EG. (1983). New Zealand Committee on Adverse Drug Reactions: Seventeenth annual report 1982. NZ Med J 96:95-9

McQueen EG. (1982). Drug Safety Monitoring using recorded release and results with sodium valproate. Advances in Pharmacology and Therapeutics II 6:79-89

Coulter DM, McQueen EG. (1982). Post-marketing surveillance: achievements and problems in the Intensified Adverse Drug Reaction Reporting Scheme. NZ Fam Physician 9(1):13-17

McQueen EG. (1982). New Zealand Committee on Adverse Drug Reactions: Sixteenth annual report 1981. NZ Med J 95:230-3

McQueen EG. (1981). New Zealand Committee on Adverse Drug Reactions: Fifteenth annual report 1980. NZ Med J 93:194-8

Coulter DM. (1981). Study of reasons for cessation of therapy with perhexiline maleate, sodium valproate and labetalol in the Intensified Adverse Reaction Reporting Scheme. NZ Med J 93:81-4

Phillips JS. (1980). Perhexiline maleate (pexid). Clinical Services Letter 192

McQueen EG. (1980). New Zealand Committee on Adverse Drug Reactions: Fourteenth annual report 1979. NZ Med J 91:226-9


pre 1980

Coulter DM. (1979). A comparison of scalp tingling, thirst and polyuria in patients on labetalol and metoprolol [letter]. NZ Med J 90:397

McQueen EG. (1979). New Zealand Committee on Adverse Drug Reactions: Thirteenth annual report 1978. NZ Med J 89:145-9

IMMP . (1978). Intensified Adverse Drug Reaction Reporting Scheme [editorial]. Pharmac J NZ 11-12

IMMP (1977). Intensified Adverse Drug Reaction Reporting Scheme [editorial]. NZ Med J 85:477

McQueen EG. (1977). Intensified Adverse Drug Reaction Reporting Scheme [letter]. NZ Med J 85:296-7

IMMP (1977). Intensified Adverse Drug Reaction Reporting Scheme [anonymous]. NZ Med J 85:157-8 Intensified Adverse Drug Reaction Reporting Scheme [anonymous]. NZ Med J. 1977;85:157-8


Annex 2. Letters of support for IMMP

Professor Martin A Kennedy Carney Centre for Pharmacogenomics

Dr Thomas J Moore Institute for Safe Medication Practices (ISMP)

Dr Marie Lindquist, Prof I Ralph Edwards The Uppsala Monitoring Centre WHO Collaborating Centre for International Drug Monitoring

Assistant Professor Sonal Singh Johns Hopkins Medicine Baltimore, USA

Professor A C van Grootheest Lareb Netherlands Pharmacovigilance Centre

Professor Alexander Dodoo President of the International Society of Pharmacovigilance (ISoP) and Director of WHO Collaborating Centre for Advocacy and Training in Pharmacovigilance University of Ghana Medical School

Professor Saad A W Shakir Drug Safety Research Unit, UK

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Jan 21, 2011

To whom it may concern

RE: Support for the Intensive Medicines Monitoring Program

To Whom It May Concern:

I am a drug safety researcher at the Johns Hopkins University School of Medicine in Baltimore, United

States of America. I have worked on various drug safety issues for the last 5 years with collaborations with

leading national and international researchers. I have published more than 100 scholarly articles in major

medical journals several of them related to the topic of prescription drug safety.

I am writing this letter to strongly second my support for the valuable and unique contributions to the safety of

prescription medications made by New Zealand’s Intensive Medicines Monitoring Program (IMMP). The quality of

its data, the experience and judgment of its staff as demonstrated in published scientific reports on several

ongoing concerns about drug safety with prescriptions such as varenicline make it one of the highest quality and

robust active drug safety surveillance systems in the world. The accurate information about dispensed

prescriptions, linkage to health data systems, and good participation by health professionals are unmatched by

another drug safety surveillance system.

We sincerely hope that the IMMP will be funded to continue its valuable work in prescription

drug safety important for public health in New Zealand and elsewhere.

Sincerely,

Sonal Singh MD, MPH

Sonal Singh MD, MPH Assistant Professor General Internal Medicine Department of Medicine 1830 E Monument St, St 8063 Baltimore, MD, 21287 Phone 410 955 9869 Fax 410 955 0825 Email: [email protected]

26th January 2012 To Whom It May Concern: Re: IMMP I am familiar with the work of the IMMP which has been a leading centre in international pharmacovigilance for a long time. The IMMP, under the able leadership of David Coulter, then the equally distinguished Mira Harrison-Woolrych, has established an almost unique method for studying the post marketing safety of medicines. Their method benefits from the structure of the health system in New Zealand which allows conducting of studies with long term longitudinal follow-up with rich clinical information. The reason for the success of the team in New Zealand is the enviable excellent relationship that the IMMP has established for a long time with doctors in New Zealand. Such relationship and study methodology has not been as effective in any other country in the world. Sir Austin Bradford Hill, the distinguished British scientist in the twentieth century, said that ‘no method in clinical or epidemiological research is without weaknesses’. It is the responsibility of those who lead public health to support and nurture the strengths of each method so that when the deliverables of all are combined, the picture will be clarified as much as possible with benefits to public health and to patients. It has been disappointing to see the IMMP struggling for many years in a hand-to-mouth way of funding existence. At the same time, it is an accolade to Mira and her colleagues at the IMMP that they managed to produce such excellent pharmacovigilance studies with remarkable impact, in spite of the need to keep looking over their shoulders for continued financial support. One cannot resist thinking that this is an incorrect and unfair situation for such an excellent team to be put in. It is my strong belief, based on my familiarity with the scientific output of the IMMP and other centres around the world, that pharmacovigilance and public health not only in New Zealand but further afield, need the IMMP to maintain it’s activities. The IMMP needs to be supported, not just be maintained as skeleton structure but to flourish with stable financial support. I know that it is the general belief in the international pharmacovigilance community that the authorities in New Zealand are advised to support the IMMP and help nurture it to move ahead. I am happy to provide further advice and evidence on this matter. Yours faithfully,

Professor Saad A W Shakir MB, ChB, LRCP&S, FRCP, FFPM, FISPE, MRCGP Director – Drug Safety Research Unit, United Kingdom


Annex 3. Patient information leaflet

Safer Safer medicines medicines through through monitoringmonitoring

a New Zealand programme for enhancing the safe use of medicines

A PATIENT INFORMATION LEAFLETA PATIENT INFORMATION LEAFLET

I N T E N S I V E M E D I C I N E SMONITORING PROGRAMME

The Intensive Medicines Monitoring Programme (IMMP) has been operating in New Zealand since 1977 and is based in the NZ Pharmacovigilance Centre at the University of Otago.

This pamphlet explains: the purpose of this safety monitoring programme

what information is collected and why

how you can participate in the programme.

What are the aims of the monitoring programme?The primary aim of the IMMP is to identify any unknown side eff ects of a medicine. This includes side eff ects that may be overlooked by other monitoring programmes.

We also aim to fi nd out how often some side eff ects of a medicine occur and who might be at particular risk of developing them.

As well as monitoring the safety of medicines the IMMP also studies how they are used in the New Zealand population.

We aim to ensure that our fi ndings result in actions that lead to medicines being used more safely.

Why is my medicine being intensively monitored?All medicines available in New Zealand are monitored for safety, but some medicines are selected for intensive monitoring. The reasons for this extra monitoring are as follows:

Monitoring of new medicinesBefore any new medicine becomes available for use in New Zealand it is studied and tested for quality, eff ectiveness and safety. But there is always a risk that some side eff ects will not be identifi ed until the medicine has been used by a large number of people for a long period of time. While some of these side eff ects might be minor, it is possible that some may be serious or even life-threatening.

New medicines are intensively monitored to identify

any unexpected side eff ects as soon as possible.

Monitoring of older medicinesOlder medicines may be intensively monitored:

if they are being prescribed in a new way or for a new purpose,

to follow up suspicions of a particular safety problem and to see how often it occurs and who may be at greatest risk, or

to compare the side eff ects of an old medicine with those of a newer one to see which is safer.

Older medicines are monitored to study known and

new side eff ects and to study use in a New Zealand

population.

The medicine your doctor prescribed for you is being monitored by the Intensive Medicines Monitoring Programme (IMMP).

What information is collected?Three kinds of information are sent to the IMMP by your pharmacist each time your doctor prescribes a medicine on the intensive monitoring programme.

individual patient information:your name, address, NHI number, gender, date of birth

prescription information:the name of your medicine, along with the dose and the amount and date it was dispensed.

doctor’s contact details:the name and address of your doctor

Your doctor may be sent a questionnaire by the IMMP on which to report any clinical problems you may experience while you are taking this medicine. We also check national health datasets to identify any hospital admissions or serious health events you may have experienced while taking the medicine.

Why is this information collected? so we can identify each prescription and each

adverse event with the correct person

so we can contact your doctor if more information is wanted about your experience with the monitored medicine

Is my personal information secure?Your privacy is very carefully safeguarded.

Our computer system is completely isolated and access is restricted to our trained staff . The information about you is held confi dentially. No personal information will be published in a way that would allow you to be identifi ed. You have access to your information on request and can ask for it to be corrected should you fi nd errors.

How do I participate in the programme?People who are prescribed medicines on the Intensive Medicines Monitoring Programme (IMMP) are automatically included in the programme.

You can assist the programme by telling your doctor about any clinical problems that you experience, or by informing the IMMP directly. For ways to report your experience to the IMMP please see details below.

If you do not wish to participate in the programme, you may ask to have your information deleted from our database and still continue to take the medicine. Your medical care will not be adversely aff ected by opting out of the monitoring programme.

How can I contact the programme?You can contact us by phone, fax, letter, or online.

Address any enquiry to:

The DirectorIMMPNZ Pharmacovigilance CentreUniversity of Otago Medical SchoolPO Box 913Dunedin 9054

phone: 03 479 7833fax: 03 479 7150email: [email protected]: www.otago.ac.nz/immp

How does the programme work?We ask doctors to report all clinical problems (including new symptoms or illness, accidents, worsening conditions etc.) experienced by their patients taking medicines on the programme. We want to record all these problems, even those that appear similar to common illnesses. Then any unknown side eff ects will be identifi ed as soon as possible.

We also record the age and gender of each person taking the medicine and the dosage and duration of therapy received. With this information we can calculate how often a side eff ect occurs and who is at greatest risk. For example, we may fi nd that a side eff ect occurs in 1 person in 2,000, but has a greater likelihood in people over 65 years who have taken the medicines for more than 2 years.

The IMMP also conducts specifi c studies and may ask doctors for further information, e.g. to study groups such as pregnant women. We design these studies to fi nd out more about some side eff ects, how often they occur and who is most at risk.

Finally we make sure that our fi ndings result in action. We publish IMMP results to inform doctors and pharmacists so that the medicines will be used more safely in the future. The IMMP reports its fi ndings to the Ministry of Health and also to international medicine safety bodies.

Taking a medicine in the programme does not mean

you will have to visit your doctor more frequently

or pay more for your treatment than you would

otherwise. Nor will your doctor or pharmacist have

access to information about you that they would not

have otherwise.

2013 immp summary booklet - new zealand pharmacovigilance

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