CURRENT ISSUES

The challenges facing pharmacoepidemiology

- Carlene Todd -

Society expects pharmacoepidemiology to deliver rapid answers on whether available drugs are safe, and whether they are used optimally and economically. 'That is what they need, that

is what they are paying for and that is what the public demands', said Dr Michael Rawlins from the University of Newcastle-upon-Tyne, UK. The question of how pharmacoepidemiologists should respond to this challenge was discussed by Dr Brian Strom from the University of Pennsylvania, US, at the 10th International Conference on Pharmacoepidemiology [Stockholm, Sweden; Aug 1994].

In tenns of safety. society wants to know whether products are safe in relation to their efficacy. their indications and alternative treatments. explained Dr Rawlins. In meeting this challenge. he believes that the following pharmacovigilance issues need to be addressed. • Improving single case and spontaneous reporting. • Reconciliation of reporting heterogeneity. • Better use of the system. • Prevention of attempts to combine databases. • Ensuring public confidence in the reporting

schemes.

Spontaneous reporting limited According to Dr Rawlins. spontaneous adverse

reaction reporting schemes are limited in that they are. at best, a minimal estimate of incidence and they are of almost no value in identifying long­latency reactions. As a result. there is a need to rely on fonnal methods of pharmacovigilance. including analysis of vital statistics. case registers. case-control studies and cohort studies. Each of these fonnal methods is complementary; they are referred to as the 'tool box of pharmacoepidemiology'. he pointed out.

However. we must examine whether our range of methodologies is sufficiently robust and reliable. said Dr Rawlins. He also questioned whether it is possible to expedite the planning and conduct of these formal studies.

'Socuty cannot tolerate academics fiddling around for 2 to 3 years, planning a case-control study and then llllcing 4 to 5 years to complete it'; rapid answers are wanted.

He queried whether a methodology for meta­analysis could be developed. A number of pharmaco­epidemiologists have said that meta-analyses and observational studies are inappropriate and impossible to use; these comments are unhelpful. commented Dr Rawlins. Systematic overviews used in a quantitative manner with observational data may well be possible. and fonn a technique that must be examined. The possibilities and limitations must be explored in a rigorous fashion. he remarked.

Dr Rawlins also believes that society's apparent concerns over confidentiality are inhibiting fonnal pharmacovigilance. and are. therefore. a major threat to pharmacoepidemiology in general.

'We have to resolve this confidentiality [issue] if we are to provide society with proper pharmaco­vigilance'. noted Dr Rawlins.

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Society expects available products to be used optimally - maximising efficacy and minimising toxicity. Drug utilisation research has an important role to play in this activity. in tenns of the rational use of drugs in relation to the Nairobi Declaration; i.e. the right drug. to the right patient. at the right dose. at an acceptable cost. However. Dr Rawlins questioned whether the Nairobi Declaration went far enough.

'Do we know what rational prescribing looks like? My prescribing is rational, is yours? And how can I persuade you that

my prescribing is rational and how can you persuade me that yours is?'

Dr Michael Rawlins, Professor of Clinical Pharmacology, University of Newcastle· upon· Tyne, UK.

He also highlighted 2 other important issues -whether rational prescribing can be measured and whether we have reliable leaders to promote the necessary changes.

An example of irrational prescribing was the use ofthrombolytics in the UK in 1992-1993. Utilisation was < 20% of eligible patients in some regions - it should be 65-70%. It is unacceptable that patients should be deprived of this effective. relatively inexpensive. life-saving therapy for no known reason. said Dr Rawlins. 'We canftddle around in laboratories, but frankly unless we can tackle this sort of problem . . . we are wasting our time. '

Are drugs used economically? 25-30 years ago society would not have considered

the economics of drug use. Now. because of limited resources and the increasing demand for perfected healthcare. it is of critical importance. Today. society expects available products to be used economically in tenns of health gain and opportunity cost. Dr Rawlins pointed out.

However. the following issues must be taken into account when considering pharmacoeconomics. • The discipline is too important to be left to health­

care managers; it should be undertaken by healthcare professionals.

• Pharmacoeconomics should be included in the training of clinical pharmacologists and pharmaco­epidemiologists.

• It is critical to ensure that pharmacoeconomic analyses are included in major randomised controlled trials.

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4 CURRENT ISSUES

According to Dr Brian Strom, the pharmaco­epidemiology field has been growing dramatically, as has our society. With this growth, the needs of pharmacoepidemiology have been widely applied -sometimes inappropriately, sometimes prematurely. He believes that in order to meet the challenges of pharmacoepidemiology, we need 'better science, better scientists, more science and more scientists'.

In the words of Dr Strom, 'there are no really safe biologicaUy active drugs, there are only safe physicians'. One of the goals of pharmacoepidemiology is to assist in the development of safe physicians.

Defining pharmacoepidemiology research

In general, pharmacoepidemiology research is a 3-phase process, starting with hypothesis generation and followed by hypothesis strengthening and testing. Hypothesis generation: Hypothesis generation depends on sp0n­

taneous reporting to detect adverse drug reactions (ADRs). However, this approach is a necessity ~miled by the power and type of data available from spontaneous reportilg. There is a need for: new methods for the systematic screening of adverse drug reactions; more sopNsticaIion by regUatOlS of the rll'llitations of ADA schemes; further academic expertise in these fields by local and iltemational regWtors; and understanding when spontaneous reporting can and cannot be used.

HypothesIs ItreIlgthening: Evely year worIIttWle, there are Ihousalds of ADA reports. However, because of cost, it is nol appropriate for all of these events to be followed up by formal hypothesis testilg studies. Therefore, hypothesis strengthening studies, which are 'quick and dirty versions of hypothesis IestiJg stucies', are used instead. However, much developmental work is required to enable hypothesis strengthening studies to be conduc:1ed in better, additional and alternative ways.

Hypothesis teatlng: In discussing the issues of hypothesis testing, Dr Strom believes the following.

• Mole lI1derstln:ing, partiUarly 00I1YI'tri:aIi0 II1d ooIabon1IioI" is needed between ADA resean::heiS and pharmacoepidemi. Too often these are 2 separate groups of people who do not convnunicate particuIatty well with each other. They do not under­stand the strengths and weaknesses of each other's WOI1< and their different approaches.

• New scientific methods are always needed, and pha!maco­epidemiology must develop its own methodologies.

• Epidemiology researchers need to address better questions; e.g. nolonly 'does the drug cause the reaction?" but also 'how often and in whom?'They also need processes thai will lead to better risl<Ibenefit judgments among alternative therapies and the rational repositioring of drugs.

• When addressing desig1 and cost issues in clinical studies, pharmacoepiderriol roost inckJde the expertise of ecooomists and vice versa.

The International Society of PhatmacoepiderT has begun wortdng -Mth the US FDA and the Pharmaceutical Manufacturers' Association to develop guidelines for pharmacoepidemiology studes b be used tor ~ puposes. This wi ~ serve asa rrodeI to assist in the use of phannacoepidemiology and hypothesis testing studies for regulatexy purposes and the rational use of ~ epidemiology for regulatexy decisions. - Dr Brian Strom

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