communicating a drug alert

Eur J Clin Pharmacol (1994) 47:125-132 © Springer-Verlag 1994

S P E C I A L A R T I C L E

M.C.J.M. Sturkenboom • L. T. W. de Jong-van den Berg M. C. Cornel • B. H. C. Stricker • H. Wesseling

Communicating a drug alert A case study on acitretin in The Netherlands

Received: 15 March 1994 / Accepted in revised form: 14 June 1994

Abstract In October 1990, a recall procedure was initi- ated for the teratogenic drug acitretin, and the recom- mended post- therapy contraception period after acitretin therapy was extended from 2 months to 2 years due to the possibility of its conversion to the lipophilic com- pound etretinate. The aim of the present study was to evaluate the communicat ion procedures and their effects as a drug alert from the health authorities, the pharmaceutical company and professional associations of health professionals to the populat ion at risk.

A model was used to evaluate communicat ion between three hierarchical levels. Data were obtained via semi-structured interviews and structured questionnaires. Communicat ion procedures were evaluated according to channel characteristics and by analysis of their contents. The effect was measured as whether the drug dispensers identified acitretin users, contacted physicians, and whether physicians communicated in person with the populat ion at risk.

The penetrat ion of direct mail from the health authorities and from the pharmaceutical company ranged from 97-98 % and 65-94 % at Level 2 (health professionals). The populat ion at risk was informed via personal communicat ion with health professionals, and/or the mass media. Of the women at risk, 19 % were con-

M.C.J.M. Sturkenboom ([~'). L.T.W. de Jong-van den Berg Department of Pharmaceutical Pharmacology and Clinical Pharmacy, University Centre of Pharmacy, University of Groningen, A. Deusinglaan 2, 9713 AW Groningen The Netherlands

M.C. Cornel Department of Medical Genetics, EUROCAT, University of Groningen, Groningen, The Netherlands

B.H.C. Stricker Netherlands Centre for Monitoring of Adverse Reactions to Drugs, Rijswijk, The Netherlands

H. Wesseling Department of Clinical Pharmacology, University of Groningen, Groningen, The Netherlands

tacted by a dermatologist, 30 % by their GR and 39 % by the pharmacist. 35 % was never informed by any health professional.

The Dutch health care system is adequately equipped for effective communicat ion between health authorities, pharmaceutical industry and health professionals. Due to problems with identification in terms of past exposure, subsequent personal communicat ion between health professionals and the populat ion at risk was inadequate. Therefore, the role in personal communication of health professionals should be increased, as they can rapidly identify persons at risk as a result of pre- vious exposure. In The Netherlands drug dispensers should have an important role.

Keywords Postmarketing surveillance, acitretin, Ad- verse drug reaction; etretinate, communication, mass media

Acitretin, the pharmacologically active hydrolysis product of etretinate, was registered in the Netherlands on 26th October 1989 and etret inate was withdrawn from the Dutch market on l l t h December 1989. Acitret in re- placed etret inate on the market in many European and non-European countries because of its more favour- able metabolic profile and comparable therapeutic effi- cacy [1]. The elimination half-life of acitretin is 50 h ver- sus 100-175 days for etretinate, which is strongly accu- mulated in fatty tissue [2].

Both acitretin and etretinate are used for the treatment of severe disorders of keratinisation and both are well known teratogens [3]. Due to the teratogenicity and long elimination half-life, women of childbearing potential were advised to avoid conception until at least 2 years after cessation of etretinate therapy. As acitretin is eliminated faster, the advised post- therapy con- t raception period (PTCP) was initially shortened to 2 months. However , on 23rd October 1990, the health authorities in The Netherlands and many other countries were notified that etret inate had been demonstra ted in

126

pharmaceutical company level 1: Senders health authorities

professional associations

L Direct mail

level 2: Receivers L[ physicians, drug dLst)ense~ J] < mass media Senders

I Personal communication

level 3: Receivers I population at risk I <

Fig. 1 Three level hierarchical model for the evaluation of communication processes after a drug alert

p lasma of 17 out of 30 ac i t re t in users. In 1990, therefore , the P T C P was ex t ended to 2 years after cessa t ion of aci- t re t in therapy. This warn ing had to be c o m m u n i c a t e d quickly f rom the reg is t ra t ion ho lder to hea l th author i - ties, hea l th profess ionals and to the p o p u l a t i o n at risk ( w o m e n of ch i ldbear ing age exposed to aci t ret in) .

Lit t le is k n o w n abou t the p e n e t r a t i o n and effects of a drug alert in to and on the p o p u l a t i o n at risk. The purpose of the s tudy was to eva lua te the channe l characteristics and con t en t of the messages as indica tors of the ef- f iciency and effect iveness of the c o m m u n i c a t i o n procedures for a drug alert f rom a pha rmaceu t i ca l c o m p a n y th rough hea l th author i t ies and hea l th profess ionals to the p o p u l a t i o n exposed to the drug in The Nether lands . The re levance of this case s tudy to c o m m u n i c a t i o n procedures in o ther count r ies will be discussed, since there may be m a n y analogies in the approach to drug alerts in o ther countr ies .

Subjects and methods

Setting

The source message-chalmel receiver effect (SMCRE) communication model of Berlo [4] was used to evaluate communication between senders and receivers of information at the three levels (Fig. 1).

Level 1: Pharmaceutical company, health authorities and professional associations

Information on the time lag between discovery and confirmation of the presence of etretinate in plasma of acitretin recipients and dis- closure of this information to health authorities was derived from semi-structured interviews with representatives of the pharmaceutical company and the Dutch Medicines Evaluation Board (DMEB). Representatives both of national health authorities (In- spectorate on Drugs and DMEB) and professional associations [Royal Dutch Association for the Advancement of Pharmacy (KNMP) and the Dutch Association of Dermatology and Vener- eology] were interviewed about their methods of distributing infor-

mation to prescribers, drug dispensers and the population at risk in case of a drug alert in general, and the acitretin case in particular. All representatives interviewed were influential participants in the decision making process about the drug alert in their organisation.

Level 2: Dermatologists, general practitioners and pharmacists

Questionnaires were mailed 3 months after the alert to a random sample of 200 general practitioners, and to all 386 dermatologists and 1153 drug dispensing outlets (DDO) who had dispensed acitretin according to data from the Netherlands Centre for Monitor- ing of Adverse Reactions to Drugs (NARD) [5]. By structured questions they were asked which direct mail with respect to acitretin was received, and whether they had been notified initially by direct mail or the mass media about the acitretin alert. They were also asked via structured questions how and when they had informed patients at risk and whether they had communicated with other health professionals.

Level 3: Population at risk: women exposed to acitretin aged 15-45 y

Based on recruitment by dermatologists and drug dispensers, a cohort of 199 women aged 15-45 y was established for follow up, comprising 45.7 % of the estimated total number of such women exposed to acitretin before November 1990 [5, 6]. They were mailed a questionnaire containing both structured and open questions with respect to how and by whom the news on acitretin was presented. Questions about the desire to have a child and whether the news had influenced this desire were included. The questionnaires were completed 6-12 months after the alert on acitretin had been issued. Informed consent was obtained prior to sending the questionnaires.

Outcome

Outcome was defined in terms of the effectiveness and efficiency of the communication process [7]. Effectiveness was defined as the degree to which the communication led to the desired action by health professionals and patients. Two effects were considered important. First, the ways in which and the extent to which dispensers traced and informed doctors, and doctors informed their patients. Second, whether the women involved took adequate measures, especially by adhering to the newly advised period of contraception: two years after the cessation of acitretin therapy.

Efficiency was defined as the quality of communicating effec- tively and without waste of time and resources. In other words, whether the right choices concerning channels and messages (content) were made in order to attain the effects intended in relation to the available time and resources. For the evaluation of efficiency, four items were considered of importance. The choices of channels applied were evaluated with respect to their ability to communicate the message to Levels 2 and 3, the percentage of the target population covered by them, and the rapidity of diffusion through them. The fourth item was content analysis, as described below.

Content analysis

The messages via direct mail and mass media were evaluated according to a traditional content analysis, in which frequencies of chosen units in the content are counted [8, 9]. In addition, newspaper articles were evaluated for the appearance of the messages.

The presence or absence of the following four main units of analysis were considered: • Information about the name of the company, name of the drug and the indications for drug use (drug information). These items were considered to be important because they allow the general

Table 1 Senders, channels and receivers of communicat ion

Senders Channels Receiver

Level 1 • Pharmaceutical Direct mail Level 2 company Mass media Level 2 and 3

• Heal th authorities Direct mail Level 2 Mass media Level 2 and 3

* Professional associations - Pharmaceutical Direct mail Level 2

Mass media Level 2 and 3

- Dermatological Group communicat ion Level 2

Level 2 • Heal th professionals Personal communicat ion Level 2 and 3

audience to recognize whether they belong to the target popula- t ion for communication, • Informat ion about the background of the problem of ret inoid teratogenicity, the sort of congenital anomalies and the conversion of acitretin into etret inate (background information). These items were considered of importance as they addressed the scope of the problem. • Informat ion regarding the data sheet amendments, the fact that use in women of childbearing age was contraindicated, and that women would be traced via drug dispensing outlets (consequences/actions). • Informat ion on the extension of the post- therapy contraception period from 2 months to 2 years, the advice to discontinue use of acitretin, to perform a pregnancy test when in doubt, to perform antenatal diagnostic procedures if pregnant, and the advice to contact the general pract i t ioner or dermatologist (advices). These items were considered of importance since they told users of childbearing age what to do.

Statistics

Discrete variables were analysed by chi-square statistics with Yates correction or with a Fisher's exact test if the expected cell count was below 5. Non-discrete variables were analysed by the Mann- Whitney U test for non-normal and t-test for normal distributions. Differences were considered significant at P < 0.05 (two sided).

Results

Senders, the selected channels, and the level of receivers of the communication processes are listed in Table 1.

Efficiency of information

Communication from Level 1 to Level 2

To the questionnaires which had been sent to health professionals in Level 2 a response was received from 106 out of 200 general practitioners (53 %), 168 out of 386 dermatologists (44 %), and 764 out of 1153 drug dispensing outlets (66 %).

Selected channels. The pharmaceutical industry, being the first in the chain of messengers, started the communication process by informing the national health autho-

127

HEALTH PROF£$$1ONAI~ SENDERS

DDO: (n-754)

, : ! ! ~ ~ . I"Iealth all~ol'i [.i~: 9 ~ ~::, ~ , ~ .._ _~ ~! ......

' ~ Z ~ . / 2 ~ . . . . . . . . . . . Red rand Enveioppe: ~

GP'S: (n- 103)

Health authorities: 98%

Red Hand Enveloppe: 65%

DERMATOLOGISTS: (n-161)

Health authorities: 97%

............. Red Hand Eavelopp¢: 91%

Fig.2 Penet ra t ion and overlap of direct mail stratified by sender and heaIth professional

rities four months after the peak was first discovered. To inform Levels 2 and 3, the company used direct mail by means of a 'Dear Doctor letter' in a Red Hand Envel- ope, in addition to a press release for the mass media. The health authorities used direct mail and mass media to issue a warning about acitretin. Professional associations had a variety of channels to communicate with their members. The professional pharmaceutical association can use direct mail, the telephone, facsimiles, and live line systems on computer to inform pharmacists, but only direct mail was used for this purpose. Press releases and the weekly pharmaceutical periodical were used for mass communication. The professional association of dermatologists usually communicates with its members through group communication during meetings; in the case of acitretin that was done 4 weeks after the alert. No medical or dermatological periodical was used to inform the audience.

Penetration per channel. The penetration of direct mail from the pharmaceutical company, health authorities and professional association in the target group of health professionals is shown in Fig.2. Out of 754 DDO, 749 received at least one letter (99 %). Similarly, 101 out of 103 general practitioners (98 %) and 157 out of 161 dermatologists (98 %) received at least one letter. Most health professionals received more than one letter. Figure 2 also illustrates the amount of overlap in penetration of different direct mail letters per profession. The direct mail from the health authorities obtained the highest (98-100 %) penetration per profession. Penetration of mass media into this group was not

128

percentage of persons 100

8 0

60

40

2 0 ~ :

0 DDO

[ ] mass media [ ] direct mall

DERMATOLOGISTS GP'S

Fig. 3 Type of media through which heal th professionals were first notified about the problem of acitretin. Mass media include radio, newspapers and television: direct mail includes mail from heal th authorities, 'Dear Doctor ' letter and pharmaceutical association. Summation of percentages can exceed 100 %, as some heal th professionals stated they were informed through direct mail and mass media on the same day

s a m e day, d i r e c t m a i l a r r i v e d . T h e p e r c e n t a g e s o f h e a l t h p r o f e s s i o n a l s n o t i f i e d first e i t h e r b y m a s s m e d i a ( n e w s - p a p e r , r a d i o , t e l e v i s i o n ) a n d / o r b y d i r e c t m a i l a r e s h o w n in Fig. 3. F o r g e n e r a l p r a c t i t i o n e r s a n d D D O , t h e m a j o r - i ty w a s i n i t i a l l y n o t i f i e d b y d i r e c t m a i l , w h e r e a s m o s t d e r - m a t o l o g i s t s w e r e f i r s t n o t i f i e d v i a t h e m a s s m e d i a .

Content o f Direct Mail Letter. I n T a b l e 2 t h e r e s u l t s o f t h e c o n t e n t a n a l y s i s a r e p r e s e n t e d . T h e l e t t e r f r o m t h e h e a l t h a u t h o r i t i e s h a d t h e h i g h e s t n u m b e r o f p o s i t i v e s co re s . R e q u e s t e d a c t i o n s w e r e c l e a r l y s t a t e d f o r e a c h t a r g e t g r o u p . T h e ' D e a r D o c t o r L e t t e r ' s e n t b y t h e p h a r - m a c e u t i c a l c o m p a n y n e i t h e r c o n t a i n e d b a c k g r o u n d in - f o r m a t i o n n o r i n f o r m a t i o n o n t h e r e c a l l r e q u e s t t o

c h a n g e p a c k a g e i n se r t s . T h e l e t t e r f r o m t h e p h a r m a c e u - t i c a l a s s o c i a t i o n h a d t h e l o w e s t s c o r e , as i t l a c k e d i m p o r - t a n t i n f o r m a t i o n .

Communication to Level 3: women of childbearing age exposed to acitretin

a s s e s s e d as h e a l t h p r o f e s s i o n a l s w e r e n o t t h e p r i m a r y t a r g e t g r o u p f o r t h i s m e d i u m .

O f t h e c o h o r t r e c r u i t e d , 162 w o m e n ( 8 1 % ) r e t u r n e d a c o m p l e t e d q u e s t i o n n a i r e . R e s p o n d e n t s a n d n o n - r e -

s p o n d e n t s d i d n o t d i f f e r in a g e d i s t r i b u t i o n ( P -- 0 .6)

Rapidity of information diffusion. O n S a t u r d a y , 2 7 t h O c - Selected channels. M a s s m e d i a w e r e u s e d t o i s s u e a t o b e r , t h e m a s s m e d i a f i r s t c o v e r e d t h e n e w s . O n t h e w a r n i n g a b o u t a c i t r e t i n f r o m L e v e l 1 t o t h e p o p u l a t i o n

Table 2 Quality criteria (see "Subjects and methods") and positive scores for direct mail letters, press releases per sender and newspaper articles in the three largest national newspapers (1-3)

Direct mail Press releases Newspapers

H A R H E Ph.ass. H A R H E Ph.ass. 1 2 3

Criteria bzformation on drug Name drug + + + + + + + + - Indication + + - + + + + + + Name company + + - - + - + + +

Background information Teratogenecity + + + + + + + + Congenital anomalies + - - + - - + + - Relat ion to Tigason + + + + + + + + +

Consequences~Actions Change package insert + - - - + - + + + Contraindic. fertile age + + - + + - + + + Women traced by D D O + + + + - + - + +

Advice Fertile women should stop - + - - + - - - PTCP for 2 years + + + + + + + _ + Pregnancy test if doubt + + - - + - + - + Antenata l diagnostics + . . . . . . + _ Contact GP/dermatologist + - + - - + - _ _

Totalpositive (%) 13 (93) 9 (64) 6 (43) 8 (57) 10 (71) 7 (50) 10 (71) 10 (71) 9 (64)

Appearance Surface heading (cm 2) 65 182 38 Ratio area heading/article(cmZ/cm 2) 0.25 0.45 0.14 Page(number) 1 1 3

HA, Heal th authorities; RHE, Dear Doctor letter in Red Hand Envelope; Ph.Ass., pharmaceutical professional association; 1, newspaper read by upper socio-economic class (NRC Handelsblad) [11]; 2, newspaper read by middle and lower socio-economic class (Telegraaf) [11]; 3, newspaper read by low-upper and upper-middle socio-economic class (Volkskrant) [11]

129

Table 3 Communication methods by whichwomen of childbearing age who had been exposed to acitretin before the warning were first notified about the drug-related problem

Method of communication No. of women [%]

Mass media 90 (62) Television 62 (43) Radio 4 (3) Newspaper 24 (17)

Personal communication 43 (30) Dermatologist 14 (10) General practitioner 11 (7) Pharmacist 9 (6) GP and pharmacist 3 (2) Family 6 (4)

Personal and mass media 6 (4)

No communication 6 (4)

Total 145 (100)

Missing 9

Started acitretin after warning 8

Total response 162

the women who had expected to be informed by their dermatologist, 83 % did not hear from him or her. Simi- larly, 63 % of the women who had expected to be informed by the GP were not, and 61% of the women were not told the news by their pharmacist. Six of the women (4 %) did not hear about the extended post therapy contraception period until they were recruited into this study.

Rapidity of information diffusion. The channels through which the 154 women, who had taken acitretin before the warning in 1990 first heard the news on acitretin are listed in Table 3. The first notification for 62 % of the women was via the mass media, mostly television. The first article appeared on Saturday, in a newspaper read mainly by the higher socio-economic classes. On the same day the news was broadcast on radio and television. If health professionals contacted women exposed to acitretin, this mostly happened by telephone during the week after the warning.

at risk (see Table 1). Health professionals (Level 2) were supposed to communicate in person with the population at risk, the most effective way to induce changes in behaviour [7].

Penetration per channel. The news about acitretin had been read in a newspaper by 45 % of the 162 women. Only 79 % of the 162 regularly read a newspaper, and 57% of the newspaper readers could not recall the message. Ninety-eight (60%) of the 162 women had followed the message on acitretin on radio and television, but 34 (35 %) of the 98 could not recall the message. Some women only recalled distorted information such as that the drug would be removed from the market. The presentation of articles in newspapers varied greatly. From Table 2 it follows that heading sizes, and the ratio of the size of headings and articles were larger in newspapers read by lower socio-economic classes.

According to the questionnaires, 35 % of the responding women was never contacted by any health professional, although 94 %, 31% and 39 % of the women stated that they had expected to be informed by their dermatologist, GR and pharmacist, respectively. This adds up to more than 100 %, since several women had expected to be informed by more than one health professional. In fact, 19 % of the women were actually informed by their dermatologist apart from their routine visit to the outpatient clinic, 30 % by their GP and 39 % by their pharmacist. There was no difference in the proportions of women wishing and not wishing to have a child, who were contacted by a dermatologist (RR = 0.99 95 %CI: 0.6-1.6). Women wanting a child were contacted more often by their GP (RR = 2.0, 1.2- 3.3) and/or their pharmacist (RR = 1.9, 1.2-3.0) as com- pared to women not wishing to become pregnant. Of

Content of press releases and newspaper articles. The press release from the pharmaceutical company fulfilled 71% of the content criteria, whereas press releases from health authorities and the pharmaceutical association contained only 57 % and 50 % of those items (Ta- ble 2). Content criteria were applied also to articles which appeared in the three most widely read national newspapers (Table 2), which vary according to their audience from the higher to lower socio-economic classes [10, 11]. All but one newspaper fulfilled most of the criteria for information about the drug, background information and consequences/actions. The name of the drug was not always mentioned in the heading. Most of the detailed advices was reported inadequately or was omitted (Table 2). In every newspaper at least one falla- cious statement was made, such as 'Drug taken from market' whereas it was only recalled to change the package insert.

Effectiveness of information

Effect of communication from Level 1 on Level 2

Drug dispensers were asked by direct mail from the health authorities to check in their databases to whom they had dispensed acitretin, and subsequently to inform GPs or dermatologists of women of childbearing age who had been exposed to the drug. Similarly, dermatologists and GPs were asked to inform their female patients of childbearing age who had been exposed to acitretin. Of the drug dispensers, 87 % responded to the request to trace users [5]. Among the drug dispensers responding to our questionnaire (n = 764), 51 were dispensing GPs (6.7 %); 6 answers were incomplete. Of the remaining 707, 300 contacted one or more physicians, as listed in Table 4.

130

Table 4 Numbers of physicians contacted by pharmacists about different types of patients exposed to acitretin

Patients all m + f only f only f Missing Total 15-45 y

Physicians GP 104 42 37 183 (63 %) Dermatologist 31 12 16 59 (20 %) Both 16 18 12 46 (16 %) Other 2 - - 10 12 (4 %) Total 153 72 65 300 (100)

Table 5 Methods of contraception employed by women of childbearing age exposed to acitretin during or within 2 years after acitretin therapy

No of women [%]

Method None 14 (9)

Oral contraceptive 68 (42) 50 >g estrogen 6 (9) < 50 ~g estrogen 48 (71) 3-phase 14 (20)

Injectable contraceptive 2 (1) Intrauterine device 5 (3)

Condom, diaphragm 6 (4) Sterilisation 32 (20)

Vasectomy of partner 23 (14)

Uterus extirpation/infertility 9 (5) Multiple 2 (1)

Unknown 1 (1) Total 162 (100)

Table 6 Influence of the alert on wish to become pregnant and on continuation of acitretin therapy among women with variable atti- tudes towards the wish for children

Child wish yes no uncertain Total

Acitretin therapy - Continued 5 (13) 34 (36) 7 (32) 46 (29) -Cessated 33 (83) 60 (64) 14 (64) 107 (69)

due to alert 9 ~ (27) 2 a (3) 2 a (14) 13 a (12) due to side effects 14 (42) 23 (38) 4 (29) 41 (38) dueto other reasons 10 (30) 35 (58) 8 (57) 53 (50)

-Missing 2 ( 5 ) - 1 (4) 3 (2)

Effect of the alert on child wish -Yes 27 (68) 8 (9) 15 (68) 50 (32) - N o 13 (32) 85 (90) 7 (32) 105 (67) -Missing - 1 (1) - 1 (1)

Total 40 (100) 94 (100) 22 (100) 156 (100)

Percentages were calculated with a denominator of 33, 60, 14, and 107 for child wish categories yes, no, uncertain, and the total, respectively

Only 19 % of the women were contacted by their dermatologist apart f rom a routine visit, and 30 % by their GR Although they were not explicitly asked to do so, 39 % of the women were contacted by the pharmacist .

Effect of communication to Level 3

The aim of the communica t ion with the popula t ion at risk was to inform them about the extended PTCR and to change their behaviour by recommending them to take adequate contracept ive measures for at least 2 years after the cessation of acitretin therapy.

The methods of contracept ion employed by the women during or within 2 years after cessation of acitretin therapy are given in Table 5. Nine percent of the women did not practice any contracept ive method. Of the oral contraceptives used, low dose estrogens were most f requently taken. The influence of the acitretin alert on the desire for pregnany and cessation of acitretin therapy is shown in Table 6. A large propor t ion of women ceased to take acitretin for other reasons than the alert. However , the propor t ion of women continuing on acitretin to use was higher amongst women without than in those with the desire for pregnancy (RR =2.9, 95 %CI:1.2-6.9). The intention to become pregnant of a large propor t ion of the women (32 %) was negatively influenced by the alert. For obvious reasons, the influence was most p ronounced among women, wishing to become pregnant and among women who were uncertain about this. Eight women not wishing to become pregnant developed an even more negative att i tude towards having children.

Discussion

The study has shown that informat ion about acitretin was adequate ly diffused f rom the health authorities, the pharmaceut ica l professional association and the pharmaceut ica l company to health professionals. Yet, overall effectiveness was poor due to inadequate personal communica t ion with the populat ion at risk. Al- though communica t ion be tween a pharmaceut ica l company and consumers in case of a serious adverse drug reaction is not de termined by s ta tutory regulations [12], patients have the absolute right to be fully and immedi- ately informed about possible risks of the drugs they take and to react accordingly. In the case of the acitretin alert, three potent ial t ime lags in the informat ion process may be distinguished.

First, the t ime lag within the company be tween discovery of the drug-related p rob lem and notification of the health authorities (4 months) . This may seem long, but validation of such a finding may require some time, and it is justified in view of the unwanted effects of needlessly arousing public concern.

Second, a potent ia l t ime lag may result f rom inadequate or delayed communica t ion to health professionals. Hea l th authorities, pharmaceut ica l company and the pharmaceut ica l professional organisat ion communicated within 5 days by direct mail, which appeared to be the best choice in view of the communica t ion goal, time, and resources. Direct mail is fast and cheap, and can be tai lored to the person or profession addressed. Clearly,

the letter from the health authorities achieved the highest penetration of all direct mail sent, and its content was most complete and was geared to the different professional groups informed. As a result of the good content and penetration of the letter from health authorities, and the poor content of the 'Dear Doctor' letter and the letter from the pharmaceutical professional organisation, these did not contribute much to the overall penetration and eventual effectiveness of direct mail. An important explanation for the high penetration of the letter from the authorities may be that such letters are infrequent and that doctors can clearly distinguish them as distinct from the common commercial information from pharmaceutical industries. Therefore, alterna- tive fast communication methods with high attention value and penetration should be employed in cases of drug alerts. Although the Red Hand Envelope was in- vented and introduced for this purpose, the variable penetration of the Red Hand Envelope among different health professions may be explained by insufficient pro- motion of its meaning and importance, as exemplified by the fact that during 1989-1991 47 % of recall letters were issued in a normal envelope [13]. Since professional associations often communicate with their members by mail, other available communication channels should be employed, in the case of drug alerts, such as facsimiles and live-line systems. Although group communication by dermatologists could have been an effective way to get a message across [7], the time lag was a disadvantage that outweighed all its potential advanta- ges. Despite the refusal of senders at Level i to communicate with health professionals via newspapers, radio or television, the use of mass media was deemed neces- sary in view of the urgency of the message and the need directly to inform the population at risk. This approach should be used only if a drug-related problem is urgent or if it concerns an OTC product. Although the exposed population was the primary target for the mass media, it is clear that health professionals were also part of the audience. The high proportion of health professionals notified by mass media may have two cau- ses; first, the newspaper that first covered the news is read mainly by members of higher socio-economic classes, and second, the news was broadcast during the weekend. Since messages communicated by mass media are less tailored to specific health professionals, and health professionals may find it irritating to be notified via mass media, information through mass media will be less effective than information received by direct mail.

A third potential time lag that probably caused a substantial delay in the information process resulted from the inadequate personal communication by health professionals with the population at risk. Most women were notified by the mass media. Despite their ability to inform rapidly, mass media are less suitable for pro- ducing changes in behaviour [7, 9]. Since it requires time and effort to identify a target population for personal communication, mass media may be useful for issu-

131

ing acute drug alerts, after which persons at risk may ob- tain additional information by themselves. The mass media may advise users of a drug to contact their physician. The percentage of people at risk who were notified by different channels in the study of Carocci on cyanide-laced Tylenol was compatible with that found in our study. In the Tylenol case, mass media and personal communication notified 70 % and 27 %, respectively, of the target population [14].

The effectiveness of direct mail varied greatly among the different health professionals. As a direct result of their high degree of computerisation of information about individual exposure to drugs, pharmacists effec- tively traced users of acitretin [5], and informed GPs and/or dermatologists about their female patients. As pharmacists not only contacted the physicians of women at risk but also those treating older females and men, too, it is impossible to draw a definite conclusion about the percentage of pharmacists who fulfilled the request to inform the physicians of women of childbearing age. It is not known why the effect of direct mail on general practitioners and dermatologists was so moderate. X1ae most likely explanation would be the difficulty for physicians of tracing the users of a particular drug, since their patients are not indexed by exposure. The timing of the warning may also have been a problem, as it is not easy to communicate with colleagues or patients over weekends. Although it is possible that some physicians underestimated the problem, it is not likely that the poor effect might be explained by a lack of professional interest. Our results are compatible with those of a study by Soumerai, who also showed the low effectiveness of warnings issued by health authorities and manufacturer about the use of propoxyphene [15].

Despite the multi-media approach to inform the population at risk, the effect was moderate, since recall of the message 6-12 months after the warning was low, and 9 % of women did not use any contraceptive method during intake or within 2 years after discontinuation of acitretin. To deal with the poor recall and to ensure uniformity of the advice given in personal communica- tions, a uniform written message by the health authorities should be supplied, which health professionals can give to their patients. Non-adherence to contraceptive measures may be explained by the absence of a sexual relationship. However, experience with isotretinoin de- monstrated that it is better to guarantee contraception, as the lack of a current sexual relationship may change over a short period. Another reason for questioning the effect of the warning is the large number of females with a negative change in their attitude towards having children. Although it is generally known that mass communication may cause an exaggerated response [9], it is likely that a physician with a careful and adequate way of communicating the information will be able to pre- vent any exaggerated fear about future pregnancies.

This study has some potential limitations. First, the response rate of health professionals did not exceed 66 %. Of all women of childbearing age who had been

132

t reated with acitretin in the Nether lands at the t ime of the study, only 40 % re turned a questionnaire. Even if we assume that the other 60 % were all informed by a health professional, that would still leave up to 15 % who were not. It is apparent that the dissatisfaction of patients with the professional role of most health professionals was substantial. Second, since recrui tment for the follow up study was largely done with the help of dermatologists and pharmacists, the att i tude of the women involved may have been more positive towards those health professionals and the actual situation was probably worse than that measured here. Third, both health professionals and patients may have had difficulty in recalling communica t ion procedures, and their recall may vary according to the degree of involvement , e.g. in women with and without the wish to have children. It is unlikely that female patients of childbearing age would not r e m e m b e r being warned by a specific health professional in case of such an emergency. Al- though the response of health professionals reached a m a x i m u m of only 66 %, it is not likely that the penet ra- tion of direct mail among the non-respondents would have been significantly less than the 99 % found in the respondents, since doctors or pharmacis ts who were not informed would probably have been more eager to express their dissatisfaction in a quest ionnaire for the health authorities. Fourth, the study not only pertains to the communicat ion of one part icular p rob lem to one particular drug, but it is also restricted to one country.

H o w far the results can be ext rapola ted to the situation in other countries is unclear. On the other hand, there are many analogies in the approach of drug alerts in other developed countries. Most of those countries have both a regulatory agency and an inspectorate for drugs, some form of direct mail for urgent pharmaceut i - cal issues, medical and pharmaceut ica l periodicals, and similar mass media. In addition it is unlikely that communicat ions by the pharmaceut ica l company would dif- fer considerably be tween countries. Therefore communication f rom Level 1 to 2 by direct mail, and to Level 3 by the mass media may be comparab le in other countries. Major differences between countries may occur in the ability to attain personal communica t ion with the populat ion at risk, since this requires identification of the patients exposed to a part icular drug. Even though health care systems tend to vary greatly be tween countries, the overall conclusion seems justified that health professionals with a computer ised registry of drugs dispensed at the level of the individual are in the most fa- vourable position to communica te a warning to patients in case of an emergency.

Acknowledgements We acknowledge the help of all the representatives interviewed, and of the dermatologists, pharmacists, general practitioners and women responding to the questionnaires. In addition, we are in debt to Mrs. A. van Trigt for her assistance with mass media communication. The study was supported by the Inspectorate on Drugs and by Hoffmann la-Roche.

References

1. Kragballe K, Jansen CT, Geiger LMW, Bjerke JR, Falk ES et al (1989) A double blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Acta Derm Venereol (Stockh) 69:35-40

2. DiGiovanni JJ, Zech LA, Ruddel HE, Gantt G, Peck GJ (1989) Etretinate, persistent levels after long term therapy. Arch Der- matol 125:246-251

3. Howard WB, Willhite CC (1986) Toxicology of retinoids in hu- mans and animals. J ToxicoI Toxin Rev 5:55-96

4. Berlo DK (1960) The process of communication:an introduc- tion to theory and practice. Holt, Rinehart Winston, New York

5. Stricker BHC, Barendregt M, Herings RMC, De Jong-van den Berg LTW, Cornel MC, De Smet PAGM (1992) Ad hoc tracing of a cohort of patients exposed to acitretin (Neotigason) on a nation-wide scale. Eur J Clin Pharmaco142:555-557

6. Sturkenboom MCJM, Stricker BHCh, De Jong-van den Berg LTW, Cornel MC, Wesseling H (1992) Post marketing surveillance and the approach of the individual patient- a significant contribution of pharmacists. Pharm Weekbl Sci 14:G6

7. Wapenaar H, ROling NHG, Van den Ban AW (1989) Basics of information skills. [Basisboekvoorlichtingskunde] Boom, Mep- pel

8. Berelson B (1952) Content analysis in communication research. Free Press, Glencoe, Ill

9. McQuail D (1991) Mass communication theory: an introduc- tion, 2nd edn. Sage, London

10. Sturkenboom MCJM, De Jong-van den Berg LTW, Cornel MC, Stricker BHC, Wesseling H (1993) A drug alert [Alarm rond een geneesmiddel]. Research report RUG, Groningen

11. Kaiser A (1990) A world of paper [Een wereld van papier; werkwijze en uiterlijk van de Nederlandse krant] In: Bardoes J, Bierhoff J (eds) Media in the Netherlands, 6th edn. Wolters Noordhof, Groningen

12. Kimble KH (1993) Thirty years after thalidomide: still plenty to do. Int J Risk Safety Med 4:1-12

13. VanAmerongen CA (1992) Better an orange hand than a red face [Beter een oranje hand dan een rood hoofd (II)] Pharm Weekbl 127:153

14. Carocci NM (1985) Diffusion of information about cyanide- laced Tylenol. Journalism Quarterly 62:630-633

15. Soumerai SB, Avorn J, Gortmaker S, Hawley S (1987) Effect of government and commercial warnings on reducing prescription misuse: the case of propoxyphene. Am J Public Health 77:1518-1523)

communicating a drug alert

Documents