Monitoring the safety of over the counter drugs
BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7315.706 (Published 29 September 2001) Cite this as: BMJ 2001;323:706All rapid responses
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Sir,
Dr Joseph Watine [1] is absolutely right to emphasise the great
disservice a writer does to the broader acceptance of their views by
excessively referencing their own published work. As previously pointed
out [2, 3, 4, 5], this self-referencing habit is very regrettable and
unjustifiable. As previously suggested [4], it also seems to smack of
arrogance. A person who mostly references their own work, either has not
read or does not value the work of others, or always places their own work
higher. Such is certainly an arrogant attitude.
"It is axiomatic that every good piece of research, whether clinical
or experimental, ought to include a perusal of the literature," [6]
Such are those who cannot even be bothered to conduct a proper
literature search and read what others have to say, or they have an
excessive interest in their own work. This suggests a bias in their
research that could lead to a suspicion of unreliability.
The only situation in which self-referencing might for a short time
seem justified, is in the case of an original pioneer, a person who
genuinely opens up a new field of research and who for some time stands
alone as a recognised figure of authentic genius or the 'acknowledged
expert' in that domain. Even then, this would only be a temporary state
of affairs and never the ingrained habit seemingly possessed by Dr Ernst
[2].
Having read much of Dr Ernst's work, I would have to say that he can
in no sense claim such a position of great genius - primarily because
everything he publishes betrays the same sceptical and impatiently
dismissive attitude towards CAM, which he always seeks to measure with a
reductionist ruler and to judge by the molecularising, 'bottom-up'
mentality of the in-vitro laboratory scientist -- an approach that is so
woefully at variance with the 'top-down', complexifying, in-vivo and
psycho-social traditions of the CAM modalities. Such an impulse truly
would be like “measuring a delicate rose with a ruler,” [7] and seems to
be as naive as it is inappropriate.
In no sense therefore, does his work possess any hallmark of
authentic genius. A position of true genius in such a field would probably
be someone who can begin to reconcile these two disparate medical
traditions and so bring some peace where thusfar there has only been
warfare.
Sources
[1] BMJ letter, Joseph Watine, 14 Nov 2001, Re: Safety of herbal
preparations,
http://www.bmj.com/cgi/eletters/323/7315/706#EL8
[2] BMJ letter, Peter Morrell, High Self-Citation Rates and a raft of
Opinions - is this research? 9 Dec 2000,
http://www.bmj.com/cgi/eletters/321/7269/1133#EL9
[3] BMJ letter, Peter Morrell, Re: self-citation, 8 Nov 2001
http://www.bmj.com/cgi/eletters/323/7320/1015#EL4
[4] BMJ letter, David Carvel, 10 Nov 2001, Re: re Self-citation,
http://www.bmj.com/cgi/eletters/323/7320/1015#EL5
[5] BMJ letter, Slight trouble with figures..., Peter Morrell, 11
July 2001,
http://www.bmj.com/cgi/eletters/322/7302/1574#EL8
[6] Owsei Temkin, An Essay on the Usefulness of Medical History to
Medicine, Bull. Hist. Med. 19.1, 1946, pp.9-47, 20
[7] G Yamey, Can Complementary Medicine be evidence-based? eWJM 2000;
173: 4-5
http://www.ewjm.com/cgi/content/full/173/1/4
Competing interests: No competing interests
Dear editor
We would like to respond to letters that were sent following our editorial
1.
We support all initiatives that provide better information to
patients, but this does not negate the need for robust and proactive
monitoring methods of the safety of OTC products. We agree that reporting
by patients, as suggested by Wade et al., is suitable for monitoring some
Adverse Drug Reactions (ADRs) which occur with over-the-counter (OTC) and
prescription only (POM) products. However, there are some ADRs that can
only be identified and reported by health care professionals.
With regard to Walmsley et al., we agree that the requirements of
obtaining and maintaining a marketing authorisation for both prescription
only and non-prescription medicines are laid down in national and EU
regulations. A marketing authorisation is only issued when a product meets
regulatory requirements for safety, efficacy and quality. Extensive
evidence of safety indeed is required before products may be considered
for re-classification to 'pharmacy-only' (P) status. Evidence of efficacy
and safety will have been gathered from pre-marketing clinical trials,
from post-marketing use, and sometimes from comparisons of safety with
other products available without prescription. However, each of these
methods has limitations regarding safety and may not predict outcomes in a
non-prescription setting 2 . Given the current drive towards self-care, it
is important that OTC medicines are subject to safety surveillance in
addition to passive spontaneous reporting. Such surveillance usually will
only be necessary for limited period of time after conversion to OTC
status.
We would like to support the view of Walmsley et al., that all health
care professionals should be encouraged to submit spontaneous reports,
especially pharmacists who are well placed to report adverse reactions
associated with over-the counter medicines. Increased use of OTC drugs
proportionally increases the occurrence of adverse effects (in absolute
numbers) 3. Unfortunately, adverse reactions caused by OTC drugs are less
likely to be reported by the consumer or the medical practitioner, than
those associated with POM 4. The point we wish to make is that because of
the likelihood of under-reporting, spontaneous reporting schemes alone are
insufficient to monitor the safety of OTC products, and should be
complimented by other methods. We disagree with the statement of Walmsley
et al., that pharmacists are less likely to suffer from the constraints
surrounding submitting reports than are general practitioners. One need
only read the Pharmaceutical Journal to understand the pressures that many
community pharmacists endure. In any case, the contribution by community
pharmacists to the yellow card scheme has not been fully evaluated.
We have repeatedly demonstrated that Prescription Event Monitoring
provides a valuable addition to pharmacovigilance of POM products in the
UK. Although pharmacists responded well to pilot pharmacovigilance
projects5, we agree that a more robust system is needed. It is clear that
many community pharmacy companies, including Boots the Chemist, are
investing greatly in computerised systems. By utilising computerised
patient medication records and advanced Point of Sale systems that appear
to be already in place, one could systematically collect data on non-
prescription medicine use with little extra burden to workload. The idea
that a pharmacist would need to personally log details is obsolete when
such technology is abundant.
The withdrawal of phenylpropanolamine-containing products highlights
the concern that not all medicines are proven safe before they are re-
classified. Our editorial merely contributes to the vision for ways to
improve post-marketing surveillance. Our vision will only bring medicines
sold OTC in line with POM products in using proactive methods (with
modifications that take into consideration the differences between POM and
OTC products). This will increase the confidence in the safety of OTC
products and may even facilitate regulatory decisions regarding POM to OTC
conversions.
Deborah Layton research pharmacist
Saad AW Shakir director
Drug Safety Research Unit, Bursledon hall, Southampton SO31 1AA
David Clark senior lecturer
Department of Pharmacology, University of Otago, Dunedin, New Zealand
Email: saad.shakir@dsru.org
References
1.Clark D, Layton D, Shakir SAW. Monitoring the safety of over the counter
drugs. [letter]. BMJ 2001;323:706-707
2. Schmid B. The safety assessment of over-the-counter products. Arch
Toxicol 1995;17:305-311
3. Meyboom RHB, Egberts ACG Gribnau FWJ, Hekster YA. Pharmacovigilance in
Perspective. Drug Safety 1999;21(6):429-447
4. Thomas DHV, Noyce PR. Over The Counter Drugs. The interface between
self medication and the NHS. BMJ 1996;312:688-691
5. Sinclair HK, Bond CM, Hannaford PC. Pharmacovigilance of over-the-
counter products based in community pharmacy: a feasible option?
Pharmacoepidemiology and Drug Safety 1999;8:479-491
Competing interests: No competing interests
As interesting as Professor Edzard Ernst’s last e-letter [1] might
sound, I am sorry to say that he has made 3 out of 4 of his references to
his own publications and thus gives a 75% self-citation rate! Old habits
die hard heh?
Competing interests: No competing interests
Clark et al1 plea for a robust method of surveillance of adverse
reactions associated with 'over the counter' medicines. I agree but would
hope that herbal medicinal products (HMPs), which are usually marketed as
dietary supplements, should be included in such surveillance. This seems
important because of the immense popularity of HMPs within the British
population2, because of the fact that HMPs are by no means free from
adverse effects3, and because consumers' attitude towards HMPs hinders
reporting of adverse events 4. UK doctors and pharmacists usually have
little knowledge of HMPs. Thus, surveillance of HMPs would also require
that healthcare professionals familiarise themselves with the most
essential facts3 on this subject. In the interest of consumer safety, we
should not ignore the potential of HMPs to do harm.
E Ernst,
Department of Complementary Medicine, University of Exeter
References
1. Clark D, Layton D, Shakir SAW. Monitoring the safety of over the
counter drugs. We need a better way than spontaneous reports. BMJ
2001;323:706-7.
2. Ernst E, White AR. The BBC survey of complementary medicine use in the
UK. Complement Ther Med 2000;8:32-6.
3. Ernst E, Pittler MH, Stevinson C, White AR, Eisenberg D. The desktop
guide to complementary and alternative medicine. Edinburgh; Mosby, 2001.
4. Barnes J, Mills SY, Abbot NC, Willoughby M, Ernst E. Different
standards for reporting ADRs to herbal remedies and conventional OTC
medicines face-to-face interviews with 515 users of herbal remedies. Br J
Clin Pharmacol 1998;45:496-500.
Competing interests: No competing interests
Editor,
Many of those who read Clark’s editorial on monitoring the safety of
over the counter medicines1 must have gained the impression that there are
no systems currently in place to monitor the safety of medicines sold over
the counter. It may come as a surprise to the authors that all
pharmaceutical companies already have a “statutory compulsion” to monitor
and report adverse drug reactions as part and parcel of obtaining a
marketing authorisation. In fact all medicines, (prescription, pharmacy
and general sales) are subject to exactly the same requirements in terms
of pharmacovigilance.
Furthermore, over the counter medicines have always been included in
the yellow card scheme, and healthcare professionals are actively
encouraged to report adverse reactions on these products. The inclusion of
community pharmacists in the yellow card scheme in November 1999 provided
an extra level of vigilance for all medicines, including those sold over
the counter. Although the yellow card scheme has the limitations of any
system that relies on spontaneous reports from healthcare professionals,
these limitations are the same for both prescribed and over the counter
medicines. Pharmacists are particularly well placed to report adverse
reactions associated with over the counter medicines, and may be less
likely to display the diffidence and complacency identified by Clark as
reasons for under-reporting by doctors.
Clark calls for a “practical yet scientifically robust” method of
safety surveillance for medicines sold over the counter. Asking
pharmacists to record details of over the counter purchases is anything
but practical, and no evidence is given to support the assertion that this
would help ensure that products are not used inappropriately, or that it
would help form part of a “scientifically robust” method of safety
surveillance. Community pharmacists already supervise the sale of all
pharmacy medicines, and, in our company, general sales medicines as well.
It could be argued that this level of supervision is at least as good as
that given for repeat prescriptions, where it is often the case that a
patient has not seen the prescribing doctor for some months.
Few would disagree that the safety of medicines is paramount and that
current systems for monitoring the safety of medicines are imperfect. The
real issue is how to improve post-marketing safety surveillance for all
medicines; there is no need to make a separate case for medicines sold
over the counter.
James Walmsley
Senior Medical Advisor
Graham Marshall
Head of Medical Services
Boots The Chemists,
Thane Road,
D90 East F08,
Nottingham
NG90 1BS
E-mail: james.walmsley@boots.co.uk
1 Clark D, Layton D, Shakir S. Monitoring the safety of over the
counter drugs. BMJ 2001; 323: 706-7
Competing interests: No competing interests
Response to journal: re: Patients can do more than just treat
themselves.
The Editor,
We appreciate Dr Wade’s agreement1 with our concern that there is a
growing need to monitor the safety of over-the-counter (OTC) medicines
under conditions of use in the community2.
We are, however, surprised by his statement that the solution we
propose has similar problems to the current systems of surveillance. We
proposed that a modified system of prescription event monitoring (PEM)
could be used for OTC medicines: that is, Pharmacy Prescription Event
Monitoring (P-PEM). In this, Pharmacists would be required to maintain
computer records of all Pharmacy only (P) medicines purchased, including
names and addresses of purchasers and the reason for use.
PEM, has the advantage over simple reporting systems in that cohorts
of the majority of patients who have been prescribed selected medicines
are available from NHS prescription records in England or from other
sources such as pharmacy records or duplicate prescriptions in New
Zealand3. In the New Zealand system of PEM, known as the Intensive
Medicines Moniotoring Programme (IMMP), comparisons of drug company
medicine sales figures with figures from prescription returns by
pharmacists has shown that returns are high (86%). Thus, in contrast to
voluntary reporting systems, in PEM the numbers of patients prescribed
selected medicines (denominator values) are known with a high level of
accuracy for epidemiological studies, as well as names and addresses of
patients and prescribers for further follow up.
As stated, our proposed system involves pharmacists maintaining
databases for P-status drugs, as they do for medicines prescribed by
doctors. Cohorts for P–PEM follow up surveillance of selected P drugs
would then be obtained by requesting pharmacists to provide details from
their databases. From the New Zealand experience with IMMP, if
pharmacists are convinced of the value of maintaining the records, returns
should be close to complete. Outcome data would be obtained by sending
written and/or telephone questionnaires to the patients or, if necessary,
their doctors.
Our proposed method thus has similarities to the method described by
Dr Wade. However, in his system, cards filled in by patients following
the purchase of the medicine are used to obtain records necessary for
further investigations. We acknowledge that use of consumer
registration cards, followed up by written and/or telephone
questionnaires, may provide a useful database for epidemiological
investigations of medicine safety. The information obtained could be
complementary to that provided by using pharmacy-maintained records. We
would like assurance from Dr Wade that the number of completed cards
returned from patients is close to the numbers of OTC medicines purchased.
1. Wade A. G. Patients can do more than just treat themselves.
BMJ.com. Rapid response, Oct.6th 2001.
2. Clark D. W.J, Layton D, Shakir S. A. W. Monitoring the Safety of the
Over the Counter (OTC) products (Editorial). British Medical Journal,
323: 706 – 707, 2001.
3. Coulter D. M. The New Zealand Intensive Medicines Monitoring Programme
in Pro-active Safety surveillance. Pharmacoepidemiology and Drug Safety,
9: 273-280, 2000.
Yours sincerely,
David Clark
Competing interests: No competing interests
The editor,
Clark et al raise an important issue related to the safety of
pharmacy provided and OTC medication. As increasing numbers of drugs are
licensed to be sold OTC, there is a growing need for the safety of the
drugs themselves and their interactions with prescribed medication to be
carefully monitored.
The solution proposed for P medication, however, appears to me to be
dogged by the problems faced by current systems of surveillance of
prescribed medication – underreporting engendered by complicated systems,
time lag and expense. OTC medicines present an even greater problem.
The philosophy of switching medication to P or OTC is to empower the
patient to participate more fully in his or her own health care. Why not
extend the same philosophy to safety monitoring? A card enclosed with the
medication invites all users to register as consumers – we already do this
for consumer electrical products. Simple postal questionnaires
supplemented if necessary by telephone follow-up can provide good quality
data on not only side effects but also efficacy. 1Our unit has already
conducted two successful pilot studies based on this model and is
currently attempting to set up a full-scale trial.
1. Fisher S, Bryant SG. Postmarketing surveillance: accuracy of
patient drug attribution judgments. Clin Pharmacol Ther 1990;48(1):102-7.
Competing interests: No competing interests
Value Media Management inc. has developped a platform of
communication on self-medicating drugs. This platform is the combination
of a database containing information of all OTC products sold in Canada. (
Including natural products) the databased was developped by pharmacists
and is managed and updated by outside pharmacists ( ie; non employees of
VMM)VMM has gainned the support of both The Quebec Order of Pharmacists
and The Ontario College of Pharmacists. The bata base is made available to
consumer via a viewing unit installed above the shelving structure where
these OTC products are available. The platform is activated by consumers
themselves, by simply exposing the UPC code of the desired product to an
optic scanner anchored to a shelve located just under the viewing unit.
The unit has two flat screens. One provides the information on the scanned
product. The other provides a health tip related to the product scanned.
VMM is now available in all Wal-Mart drugstores within the Quebec market
place. Consumer consult the units at an average rate of almost 600 times
per week per store. The participating pharmacists enjoyed the platform for
the supports it gives them in educating both consumers and floor prosonnel
as well. VMM is on the edge of further testing its platform with the
collaboration of Health Canada. If all goes well, VMM will expand its
service across Canada. The health tip/information combination is key to
deliver impirically based information/warning on both benefits and
potential side effects of any OTC drug.
More information is available on demands
Competing interests: No competing interests
The New Zealand Parliamentary Regulations Review Select Committee
found that the Center for Adverse Reactions to Medicines system (CARM) in
New Zealand is nothing more than a notification system; not a rigorous
monitoring system. (1)
This system is supposed to receive adverse reactions reports to
drugs, classify them and enter them into a database. Unfortunately, it
also enters reactions reported to vitamin, mineral and herbal supplements
whilst acknowledging very little understanding of them. Even rashes are
classified as adverse reactions which are then quantified and used to
umpugn the good name of the dietary supplement industry. It’s under
resourced, and has to charge folk who want to make use of the data.
In 1999 I wanted to access adverse reports to dietary supplements. It
costs $450 to obtain even a limited list of adverse reaction reports which
included a great number of codes. In other words, much of the information
is useless unless one is able to break the codes (which isn’t difficult
with a bit of lateral thinking.) What was able to be shown was that fully
75% of the adverse reactions classified as being related to dietary
supplement vitamin formulations were in fact medicinal compounds marketed
by a single company. Other examples of misclassification included an
adverse reaction reported to infant milk formula (cow milk based) was
classified as a herbal. Another included an adverse reaction to a company!
These figures had been used in an attempt to discredit the dietary
supplement industry on national television. Had CARM been funded properly,
it would have been possible to ensure that the quality of the database was
such that meaningful information could be ascertained and fed back into
the system to ensure evidence-based decision-making. Many of the adverse
reaction reports alleging safety problems were in desperate need of
further information – a well-resourced unit would be able to undertake
such.
CARM is an excellent example of the need to look past a simple
‘monitoring/reporting paradigm. Any system needs to include monitoring,
evaluation and timely feedback systems to ensure that not only is a
culture of best-practice is attained, but that the consumer has confidence
in such a system.
Perhaps an explanation of what monitoring is or isn’t would be useful
here. Monitoring is simply a step in the control process. In management
terms, the control process is about ensuring that objectives are being
met. Presently the health system has no objectives regarding adverse
reaction reporting. To be effective, objectives, developed as a part of
the planning process, should be what is called SMART. They should also be
challenging and linked to rewards. Until such a system is up and running
robustly, and non-punitively, it is unlikely that any industry will,
willingly, want to be a part of it.
Monitoring can be divided into four basic types; Baseline
monitoring, which establish baseline reference conditions that can be used
to quantify a change that might be due to management activities;
Implementation monitoring, sometimes called compliance monitoring, which
simply tracks systems to see if management direction is accurately
interpreted and followed; Effectiveness monitoring is intended to measure
whether progress is being made towards an objective; and Validation
monitoring which seeks to verify the assumed causal linkages between cause
and effect.
Regarding adverse reaction monitoring systems, I'm not aware of any
of these types of monitoring being proactively utilised.
Given the ubiquitous nature of foods, dietary supplements, OTC and
prescription medicines, perhaps there is a need for a well funded, well
managed properly focussed global monitoring system that integrates all
four types of monitoring types and actually provides meaningful and
balanced data that is used equitably. For example, why has Australia
imposed the harshest warning labels reagrding any orally consumed
substance on the planet on any royal jelly, including the word
'fatalities' when the data is so flawed, and even fabricated, the total
number of serious alleged adverse reactions is low (single digits), and
that drugs with thousands of deaths attributed to normal use (such as
Aspirin and paracetamol) have no such labels?
Until decision aids are robust, purpose built and kept honest, and
utilised objectively, that old adage, garbage in -- garbage out is perhaps
relevant. Given the wealth of knowledge that we have about adverse
reactions to drugs, supplements, foods, etc -- perhaps we need to consider
entering a wisdom-age if we are to make a real difference in reducing
adverse reactions to consumers and improving their wellbeing.
Unfortunately, misused decision aids mislead policy makers (2) who
often over-rely on experience which leads to making the same mistakes with
increasing levels of confidence.
Other interests: RL is also executive director of the National
Nutritional Foods Association and member of the New Zealand Ministry of
Health Sentinel Event Project working group. Research interests include
evidence-based decision making in public management.
(1) HUNT, Rt Hon Jonathan, (1999) "Complaint relating to the New
Zealand Food Standard 1996, Amendment No. 11: Report of the Regulations
Review Committee, FORTY-FIFTH PARLIAMENT" July
(2) Brown, R. (1999) How misused decision aids mislead policy makers,
Competing interests: No competing interests
Re: This Self-citation Curse
Although it is in a letter rather than a scientific work, I cannot
help noticing that Peter Morrell's own self-citation rate is 3/7=43%.
Competing interests: No competing interests