Patients' and physicians' perspectives on pharmacogenetic testing

RESEARCH REPORT

Patients’ and physicians’ perspectives on pharmacogenetic testing

†Author for correspondence1Georg-August-University Göttingen, Department of General Practice/Family Medicine, Humboldtallee 38,37073 Göttingen, GermanyTel.: +49 (0)551 39 9537;Fax: + 49 (0)551 39 9530;E-mail: [email protected] Göttingen, Department of Clinical Pharmacology,Germany

Keywords: attitude of health personnel, delivery of healthcare, ethics, patient acceptance of healthcare, pharmacogenetics

10.2217/14622416.7.1.49 © 20

Introduction: The integration of pharmacogenetic testing into routine care will, in part, depend upon the patients’ and physicians’ acceptance of these tests. Empirical data regarding patients’ and physicians’ views on pharmacogenetic testing are lacking. Objectives: To explore patients’ and physicians’ perspectives on the potential implications of pharmacogenetic testing, particularly focusing on asthma, and to analyze the possible determinants of their expectations, hopes and fears. Methods: We conducted telephone interviews with patients with asthma or chronic obstructive pulmonary disease taking part in a larger pharmacogenetic study, in addition to general practitioners (GPs) from a different region in Germany. A total of 328 patients and 378 GPs were invited to participate. Determinants of their attitudes toward pharmacogenetic testing were assessed using logistic regression analysis. Results: Informed consent to participate in this study was given by 196 patients (60%) and 106 GPs (28%). Most patients (96%) and physicians (52%) appreciated the availability of pharmacogenetic tests for a disease such as asthma. Approximately a third of the patients worried about potential unfavorable test results (35%) and violation of privacy (36%). Female patients were more likely to have a fearful attitude (odds ratio [OR] = 2.85; 95% confidence interval [CI] = 1.58–5.12). Younger patients were generally more likely to be hopeful about the usefulness of pharmacogenetic testing (OR = 2.12; CI = 1.01–4.46). The GPs’ concerns were mainly related to the possibility that patients might either be put under pressure to be tested (72%) or be disadvantaged at private health insurance agencies (61%). The nature of the responsible institution, the clarity of the research aim and explicit informed consent from patients influenced a physicians’ decision regarding whether to support a pharmacogenetic study. Conclusion: The concerns of patients and GPs differ somewhat with respect to negative psychosocial consequences, discrimination or violation of privacy. Development of information for physicians and patients would be helpful in preventing unrealistic fears or hopes.

Due to genetic variation, people differ in thetransport, metabolism and targets ofmedications [1]. Pharmacogenetics employs theuse of genetic information to facilitate the selec-tion and dosage of medication for individualpatients [2–4]. Though pharmacogenetic testing isstill under development [5–7], it will becomeincreasingly important in medical care [8]. In thefuture, pharmacogenetics may permit theadministration of an individualized drug treat-ment [9]. Approximately 100,000 patients world-wide per year are already exposed topharmacogenetic testing during clinical drugresearch. In some medical disciplines, such as thediagnosis of coagulation disorders, testing of theunderlying causes by molecular genetic meanshas become almost routine.

However, ethical concerns, including viola-tion of confidentiality, stigmatization and socialpressure to accept pharmacogenetic testing, mayarise [10]. Pharmacogenetic testing can be

distinguished from conventional tests by the factthat the genetic information represents a non-transient individual attribute characterizing, notonly the subject being tested, but also to someextent, their family members [11].

There are some genetic variations that indicatenot only an insufficient response to medication,but also an increased risk of developing a specificdisease, such as Alzheimer’s disease [12]. Affectedpatients may be at a disadvantage at work and/orhealth insurance agencies due to unfavorablegenetic dispositions that may be associated withincreased medical costs or time off work [13–15].Some authors argue that personal genetic informa-tion will inevitably be disclosed to health insuranceagencies or pharmacists when patients receive per-sonalized drugs [16]. Many of these issues are sharedby both genetic and nongenetic tests [17].

Future implementation of pharmacogenetics indaily medical practice will ultimately dependupon patients’ and physicians’ acceptance of, and

06 Future Medicine Ltd ISSN 1462-2416 Pharmacogenomics (2006) 7(1), 49–59 49

RESEARCH REPORT – Rogausch, Prause, Schallenberg, Brockmöller & Himmel

50

requests for, these tests [18–21]. For most medicalconditions, general practitioners (GPs) are apatient’s primary contact, and as such are likely toplay a key role in the communication of the neces-sity and results of pharmacogenetic tests. Whilemany theoretical considerations have been voiced,there is still a lack of empirical data concerning theactual views of patients and GPs [22].

The aims of this study were:

• To explore patients’ and physicians’ expecta-tions, hopes and fears regarding pharmaco-genetic testing

• To analyze possible attitude determinants

The results obtained should contribute informa-tion regarding the specific perspectives ofpatients and GPs to pharmacogenetics.

MethodsStudy designA cross-sectional survey based on telephoneinterviews among GPs and patients with asthmaor chronic obstructive pulmonary disease(COPD) was conducted. A questionnaire forpatients and physicians, derived from a literaturereview [22], focused on the psychologic, family-related, social, and ethical consequences ofpharmacogenetic testing.

As pharmacogenetic testing is an unknownsubject for most patients and some physicians,the study participants were first provided with astandardized information sheet (available uponrequest). This leaflet gave a definition, an exam-ple of pharmacogenetic testing and explained thetesting procedure. It also broadly described pos-sible advantages (for example, to find out thebest medication dosage) as well as possible risks(for example, violation of privacy). Interviewscould then be conducted on a comparable basis.

At the beginning of each interview, the inter-viewer checked, in a standardized manner,whether or not the patient or doctor had under-stood the definition of pharmacogenetic testingand repeated the explanations using asthma as anexample. Telephone interviews took approxi-mately 15 minutes. The patients’ socio-demographic data, as well as their quality oflife [23], had been assessed in the larger study.

The questionnairesThe questionnaires comprised open and closedquestions concerning pharmacogenetic-relatedconcerns, hopes and expectations, in additionto other specific aspects, for example privacyissues. A couple of example questions from

both the patient and physician questionnairesare given below.

Examples from the patient questionnaire:

• Would you agree to a pharmacogenetic testprior to receiving a prescription for yourasthma? ‘yes’/‘no’/‘don’t know’

• Are you (very/slightly/not) worried about thepossibility that a pharmacogenetic test may,by chance, reveal that you possess additionalrisk factors for another disease that you wereunaware of?

Examples from the physician questionnaire:

• Would you recommend a pharmacogenetictest before writing a prescription for asthma?‘yes’/‘no’/‘don’t know’

• Are you (very/slightly/not) worried about thepossibility that patients may feel ‘different’ or‘inadequate’ due to an unfavorable test result?

We discussed, revised and piloted the informationsheet and questionnaires in order to maximizecomprehensibility, neutrality of questions andinformation received (ten pilot interviews each).

Recruitment of patients & physiciansA total of 328 patients with asthma or COPDwere invited to participate. These patients weretaking part in a larger study analyzing the associ-ation of certain genes and the response to asthmamedication. Inclusion criteria were the nonexist-ence of mental or terminal disease and the abilityto understand and speak German.

All GPs who were located in a district in thewestern part of Germany (Westphalen-Lippe)were contacted by mail (n = 378; not related toparticipating patients). A prepared reply sheet,on which willingness or reluctance to participatecould be noted, was enclosed. Physicians whodid not respond to the letter were additionallycontacted by phone.

The study protocol has been approved by theUniversity of Göttingen Ethics Committee.

StatisticsThe frequency and intensity of patients’ or phy-sicians’ hopes, concerns and expectations inabsolute and relative numbers were first calcu-lated. In order to analyze associations betweenthese hopes and worries (criteria) and possibleinfluences (predictors), simple logistic regres-sions were performed. Therefore, we calculateda sum score for the questions pertaining tohopes and concerns from the patient inter-views. We then divided these scores into two

Pharmacogenomics (2006) 7(1)

www.futuremedicine.com

Patients’ and physicians’ perspectives on pharmacogenetic testing – RESEARCH REPORT

categories as follows. Patients who repeatedlyexpressed ‘no hope’ (and never ‘great hope’)were regarded as not having a hopeful attitude(sum score of less than 4). Subjects who wereconsistently ‘unconcerned’ (and were never‘very concerned’) were labeled as not fearful(sum score of less than 4). Both criteria couldbe identified by responses to different interviewquestions. Therefore, having a hopeful attituderegarding pharmacogenetic testing did not pre-clude being fearful with respect to issues arisingfrom pharmacogenetic testing in general, forexample protection of privacy. With regard tophysicians’ concerns, a sum score greater than 3represented a fearful attitude.

Odds ratios (ORs) and their 95% confidenceintervals were calculated to estimate the associa-tions between the potential predictors and crite-ria. For patients, predictor variables includedage, gender, education, place of residence, andquality of life. For physicians these were age,gender, place of residence, and size of practice.

Multiple logistic regression analyses wereunnecessary as only one variable was significant(p < 0.05) in simple logistic regression. The Sta-tistical Analysis Software (SAS, NC, USA)package, Version 9.1 was used for data analysis.

ResultsSampleA total of 196 patients (60% of 328 patientsaddressed) and 106 GPs (28% of 378 GPs)agreed to participate by written informed con-sent (Figure 1). 55% of the patients were female;

the mean age of the patients was 57.6 years(range: 23.9–81.2; median = 60.7). We foundno evidence of systematic differences (forexample, with respect to age, gender or dura-tion of illness) between participating andnonparticipating patients.

Figure 2 shows the process of recruitment ofGPs. The main reasons given for physicians’nonparticipation were either ‘no time’ (92/242,38% of the refusing GPs), ‘no interest’ (32%)or ‘nonparticipation as a matter of principle’(17%). In the physician sample, 25% werefemale. Compared with German reference data(provided by the National Association of Statu-tory Health Insurance Physicians [101]), partici-pating GPs were more likely to be male, butthis did not differ from participation recordsfrom other primary care studies [24]. The agedistribution was as follows: 8%: 30–40 years,42%: 40–50 years, 37%: 50–60 years,14% > 60 years.

Consent to pharmacogenetic testing & expectationsThe patients’ viewThe vast majority of patients (95.9%; 95% con-fidence interval [CI] = 92.1–98.2%) wouldaccept pharmacogenetic testing prior to receiv-ing a prescription for asthma medication. Onlythree of 196 patients would decline testing andfive patients were undecided. Nearly 80%(153/196) of the patients wanted to be informedspecifically by their GP (13.3% by a specialist;7.7% by a geneticist).

Figure 1. Study participation by patients with asthma or COPD.

COPD: Chronic obstructive pulmonary disease.

949 patients invited to participate in a large study(mean = 24.3 ± 8.7 patients/practice)

341 patients gave informed consent(mean = 8.53 ± 4.39 patients/practice)

328 patients examined by a study nurse(mean = 8.18 ± 4.31 patients/practice)

196 patients (60%) consented to take part in interview study

516 patients did not respond; 92 patients refused to participate

13 patients withdrewinformed consent

132 patients refused to participate in interview study

Pharmacogenomics

51

RESEARCH REPORT – Rogausch, Prause, Schallenberg, Brockmöller & Himmel

52

The patients were optimistic that pharmaco-genetic testing would prevent them from takingan inappropriate or second-rate medication(Figure 3). Identifying the drug which would helpmost, and avoiding side effects, were otherimportant issues. Almost all patients (94.4%;90.2–97.2%) felt it would be advantageous toknow their genetic disposition.

The physicians’ viewApproximately half of the GPs (55/106; 51.9%;42.0–61.7%) said they would recommend apharmacogenetic test before administering ananti-asthma drug (for example, β-mimetics) ifthe fees were covered by the health insurance.Most physicians regarded it highly probable(29.3%; 20.8–38.9%) or rather probable

Figure 2. Study participation by general practitioners.

GP: General practitioner.

378 GPs were contacted by mail

Telephone interviews with 106 GPs (28%)

83 GPs initially faxed reply sheet

46 agreed to participate,37 refused to participate

275 GPs did not respond, but were contacted by phone

64 agreed to participate,205 refused to participate

20 GPs were unobtainable(e.g., mail returned to sender)

6 GPs had to be excluded(e.g., mainly worked aspsychotherapists)

4 GPs withdrew informedconsent due to personalreasons

Pharmacogenomics

Figure 3. Patients’ hopes regarding pharmacogenetic testing.

Values are percentages (and their 95% confidence intervals).

74.5% (67.8–80.4%)

25.0% (19.1–31.7%)

0.5% (0.0–2.8%)

62.8% (55.6–69.5%)

36.7% (30.0–43.9%)

0.5% (0.0–2.8%)

62.8% (55.6–69.5%)

35.7% (29.0–42.9%)

1.5% (0.3–4.4%)

0 10 20 30 40 50 60 70 80 90 100

%

Are you (very/slightly/not)hopeful about the possibility:

That a pharmacogenetic testmay prevent you from taking the wrong drug (or too high or low dose)

That a pharmacogenetic test maydetect which drug (or which dose)works best?

That a pharmacogenetic test maydetect which drug (or which drug dose) causes the fewest side effects

Very hopeful

Slightly hopeful

Not hopeful

Pharmacogenomics

Pharmacogenomics (2006) 7(1)

www.futuremedicine.com

Patients’ and physicians’ perspectives on pharmacogenetic testing – RESEARCH REPORT

(53.8%; 43.8–63.5%) that information frompharmacogenetic testing would facilitate thechoice of drug or its dosage (14.2% thought itrather improbable; 2.8% very improbable).Compared with patients, fewer physicians(58.5%; 48.5–68.0%) saw an advantage inknowing one’s genetic disposition.

Concerns & expectationsThe patients’ viewPatients were asked to give their opinions on fivestatements concerning possible concerns regard-ing pharmacogenetic testing (Figure 4). The possi-bility that a pharmacogenetic test might producean adverse result, such as the lack of a suitabledrug, worried 72% of the patients. Patients werealso anxious that information obtained frompharmacogenetic tests might not be sufficientlyprotected. In contrast, only a few patients wereworried that genetic information would be dis-closed to health insurance agencies or that theresults of pharmacogenetic tests could influence aphysicians’ prescribing decision more significantlythan their own preference. The possible detectionof a previously unknown genetic risk seemedalarming to some patients.

Should privacy not be protected, approxi-mately 70% of the patients expected problemsat work, or with an application for employment

should a test result be unfavorable. Fewerrespondents expected disadvantages at healthinsurance agencies (Figure 5). While mostpatients did not anticipate feeling ‘different’ or‘inadequate’ when confronted with an adversetest result, 40% expected to at least feel ‘pessi-mistic’ and ‘helpless’ in such a situation. Themajority of patients did not expect to be putunder pressure to accept pharmacogenetictesting in the future.

In absence of an alternative drug, more thanhalf of the patients (111/196; 56.6%;49.4–63.7%) would take a particular drug evenif it was precluded by a pharmacogenetic test (‘ifa test revealed that the only drug available wouldeither be ineffective or cause severe side effects,would you try the drug anyway or accept theresult of the test?’). Approximately 40%(79/196; 33.4%–47.5%) of the patients admit-ted that they did not completely comprehendthe consequences of pharmacogenetic testing.

Among patients, only one factor – beingfemale – was significantly associated withhaving a fearful attitude toward pharmacoge-netic testing (OR = 2.85; 95% CI = 1.58–5.12;Table 1). Age was the only significant predictorfor a hopeful attitude regarding pharmaco-genetic testing, with younger patients beingmore optimistic (OR = 2.12; 1.01–4.46).

Figure 4. Patients’ concerns regarding pharmacogenetic testing.

Values are percentages (and their 95% confidence intervals).

35.2% (28.5–42.3%)36.7% (30.0–43.9%)

28.1 (21.9–34.9%)

35.7 (29.0–42.9%)30.6% (24.2–37.6%)

33.7% (27.1–40.8%)

15.3% (10.6–21.1%)40.3% (33.4–47.5%)

44.4% (37.3–51.6%)

9.2% (5.5–14.1%)

17.9% (12.8–24.0%)73.0% (66.2–79.0%)

3.1 (1.1–6.5%)19.9% (14.6–26.2%)

77.0% (70.5–82.7%)

0 20 40 60 80 100

%

Are you (very/slightly/not) worried about the possibility that:

A pharmacogenetic test may not find adrug that is suitable for you (e.g., that available drugs won’t work or severeside effects are probable)?

The result of a pharmacogenetic test maybe passed onto unauthorized persons?

A pharmacogenetic test may, by chance, reveal that you possess additional risk factorsfor another disease that you were unaware of?

A health insurance agency may obtain information regarding your genetic dispositionwhen your doctor prescribes a targetedmedication or dose?

Your own preference could influence a physician’s prescribing decision lesssignificantly than the results of pharmacogenetic tests?

Very worried

Slightly worried

Not worried

Pharmacogenomics

53

RESEARCH REPORT – Rogausch, Prause, Schallenberg, Brockmöller & Himmel

54

The physicians’ viewPhysicians were asked to give their opinion to fourstatements regarding possible worries (Figure 6).Many of them feared that employers or insuranceagencies might exert pressure on patients to agreeto pharmacogenetic testing, and that patientsmight be disadvantaged at private health insur-ance agencies if a pharmacogenetic test showedthat they needed an exceptionally high dose of adrug. To a lesser degree, they were concernedabout how patients might react in the face ofadverse testing results, including the possibilitythat risk factors for another disease such asAlzheimer’s might be revealed.

With respect to predictors of physicians’ wor-ries, only the place of residence tended towardsignificance: physicians working in a rural areawere more likely to have a fearful attitude thanphysicians from urban regions (OR = 2.16;0.89–5.25; p = 0.09).

Perspectives on pharmacogenetic researchMost physicians (77.4%; 68.2–84.9%) wouldrather agree to pharmacogenetic studies if theywere conducted by a university (22.6% consid-ered the institution irrelevant; no doctor indi-cated a preference for studies to be performed bythe pharmaceutical industry). More than 70%

(76/106; 62.1–80.0%) would encourage theirpatients to take part in well-controlled pharma-cogenetic studies with a clear hypothesis if pri-vacy was guaranteed (13.2% would adviseagainst; 15.1% had no opinion). In contrast,many physicians (64.2%; 54.3–73.2%) wouldadvise patients against participation if theresearch aims and hypotheses were unspecified(22.6% would encourage participation; 13.2%had no opinion). In any case, physicians (85.9%;77.7–91.9%) thought that explicit permissionand informed consent from patients was neces-sary before performing a pharmacogenetic test(12.3% thought that this was not necessary;1.9% did not know).

DiscussionNearly all patients of our sample would consentto a pharmacogenetic test prior to treatment inthe hope that a targeted medication would beprescribed, that side effects could be preventedand the use of ineffective drugs avoided. Approx-imately half of the GPs would recommend apharmacogenetic test. GPs voiced greater con-cerns than patients, especially with respect topressure being exerted on patients to agree to apharmacogenetic test or disadvantages at privatehealth insurance agencies.

Figure 5. Patients’ expectations regarding pharmacogenetic testing.

Values are percentages (and their 95% confidence intervals).

0 20 40 60 80 100

%

69.4% (62.4–75.8%)27.0% (21.0–33.8%)

3.6% (1.5–7.2%)

43.9% (36.8–51.1%)55.1% (47.9–62.2%)

1.0% (0.1–3.6%)

41.3% (34.4–48.6%)

58.7% (51.4–65.6%)

35.7% (29.0–42.9%)

64.3% (57.2–71.0%)

29.1% (22.8–36.0%)

70.9% (64.0–77.2%)

In case an unfavorable test result should bedisclosed, do you believe that you would bedisadvantaged at work or job-seeking?

In case an unfavorable test result should bedisclosed, do you believe that you would bedisadvantaged at health insurance agencies?

In case of an unfavorable test result, do you believe that then you would feel ‘helpless’ or‘pessimistic’?

Do you believe that in the future pressure may be exerted on patients to agree to a pharmacogenetic test?

In case of an unfavorable test result, do youbelieve that you would then feel ‘different’ or‘inadequate’?

Yes

No

No opinion

Pharmacogenomics

Pharmacogenomics (2006) 7(1)

www.futuremedicine.com

Patients’ and physicians’ perspectives on pharmacogenetic testing – RESEARCH REPORT

Table 1. Predictors for the hopes and fears of patients toward pharmacogenetic testing.

Prevalence N (%)

OR 95% CI p-value

Predictors for a fearful attitude

Age (years):

>median (60.7) 42 (42.86) 1

<median 50 (51.02) 1.39 0.79–2.44 0.25

Gender:

Male 29 (32.95) 1

Female 63 (58.33) 2.85 1.58–5.12 0.0005

Place of residence:

Rural 51 (45.95) 1

Urban 41 (48.24) 1.10 0.62–1.93 0.75

Education:

≥secondary school**

40 (46.51) 1

<secondary school

52 (47.27) 1.03 0.59–1.82 0.92

Quality of life:

SGRQ >median (poor)

40 (42.55) 1

SGRQ <median (good)

52 (50.98) 1.40 0.80–2.47 0.24

Predictors for a hopeful attitude*

Age (years):

>median (60.7) 74 (75.51) 1

<median 85 (86.73) 2.12 1.01–4.46 0.05

Gender:

Male 68 (77.27) 1

Female 91 (84.26) 1.57 0.77–3.23 0.22

Place of residence:

Rural 88 (79.28) 1

Urban 71 (83.53) 1.33 0.64–2.76 0.45

Education:

<secondary school**

87 (79.09) 1

≥secondary school

72 (83.72) 1.36 0.65–2.83 0.41

Quality of life:

SGRQ >median (poor)

76 (80.85) 1

SGRQ <median (good)

83 (81.37) 1.04 0.51–2.12 0.93

*Attitude evaluation is based on answers to different sections of the questionnaire, so that the same patient may have both a positive attitude toward certain aspects of pharmacogenetic testing as well as negative opinions regarding other points (see methods section for details).**“Hauptschulabschluss”, i.e. exam passed after 5 years at secondary school.CI: Confidence interval; N: Number; OR: Odds ratio; SGRQ: St George’s Respiratory Questionnaire.

55

RESEARCH REPORT – Rogausch, Prause, Schallenberg, Brockmöller & Himmel

56

LimitationsIt is possible that the patient sample might bebiased, as the patients were already participants ina larger study on pharmacogenetic testing. We cantherefore hypothesize that our participants werepossibly more open-minded toward pharmaco-genetics and better informed than the averagepatient. Nevertheless, they had typical objectionswith respect to the regulatory framework, forexample, protection of privacy. However, patientswith a chronic disease are the target group forpharmacogenetic testing and, consequently, theiropinion is exceptionally relevant for the imple-mentation of pharmacogenetics into routine care.

Although the GPs’ response rate was relativelylow, it was comparable with other primary care-based studies [24]. The physicians’ appraisalsmight have been different if another indicationfor a pharmacogenetic test had been used, forexample, a severe and more difficult to treat dis-ease. Nevertheless, asthma is commonly regardedas a suitable indication for pharmacogenetic test-ing as it represents a chronic illness requiringlong-term pharmacologic intervention [25,26].

The provision of an information leaflet mighthave influenced responders’ opinions in bothdirections. Whereas the idea of future therapeutic

options itself might have favored an optimistic atti-tude of patients, the physicians’ appraisal of theusefulness of a pharmacogenetic test may havebeen higher had more detailed information regard-ing the specificity, sensitivity and the clinical valueof a pharmacogenetic test, for example, beenincluded. However, like other researchers [27] webelieved that the inclusion of some basic informa-tion was essential due to the lack of familiarity withthe topic. Therefore, it was of special importanceto describe the process of data collection on a sys-tematic and transparent basis and to keep this inmind in interpreting the results.

The patients’ perspectivePatients’ enthusiasm toward pharmacogenetictesting corresponds with results from studies ongenetic testing which found a generally highacceptance of these procedures, especially fromill or at-risk persons [28,29]. However, a recentqualitative work disclosed concerns regarding thecosts of ‘tailor-made drugs’ compared with con-ventional treatments and the potential local orglobal inequalities that may result [30]. Ashypothesized by many authors [13–15], patients inour study also worried about privacy issues, andadverse treatment at work or from health

Figure 6. GPs’ worries regarding pharmacogenetic testing.

Values are percentages (and their 95% confidence intervals).

71.7% (62.1–80.0%)14.2% (8.1–22.3%)

14.2% (8.1–22.3%)

61.3% (51.4–70.6%)26.4% (18.3–35.9%)

12.3% (6.7–20.1%)

27.4% (19.2–36.9%)

34.0% (25.0–43.8%)

38.7% (29.4–48.6%)

21.7% (14.3–30.8%)

30.2% (21.7–39.9%)

48.1% (38.3–58.0%)

0 20 40 60 80 100

%

Are you (very/slightly/not) worriedabout the possibility that:

In the future employers or health insurance agencies may exert pressure on patientsto agree to a pharmacogenetic test?

Patients may be disadvantaged when applying for admission to a private healthinsurance agency in the future, if a pharmacogenetic test showed that theyrequire an exceptionally high dose of drug?

Patients may feel ‘different’ or ‘inadequate’due to an unfavorable test result?

A pharmacogenetic test not only providesinformation regarding the assumed responseto a drug, but unintentionally also indicatesa possible increased disease riskfor Alzheimer’s disease, for example?

Very worried

Slightly worried

Not worried

Pharmacogenomics

Pharmacogenomics (2006) 7(1)

www.futuremedicine.com

Patients’ and physicians’ perspectives on pharmacogenetic testing – RESEARCH REPORT

insuance agencies. However, in contrast to com-mon assumptions, most patients did not anti-cipate experiencing negative feelings as aconsequence of an unfavorable test result.

Responding patients seemed to have a moresimplistic understanding of pharmacogenetictesting than GPs. Indeed, genetic variation isoften only one of many explanatory factors (e.g.,nutrition, smoking status, and renal function)and may be overestimated by patients withoutproper information [31,32]. Obviously, patientsassume that they will receive a clear and positivetreatment recommendation based on pharmaco-genetic testing. However, when a particular drugis not recommended and no alternative treat-ment exists, more than half of the patients wouldtake the inappropriate drug against pharmaco-genetic advice, obviously in order to personallycheck the ‘validity’ of the test result. This sce-nario poses new challenges for shared decisionmaking in primary care [33].

Approximately 40% of the patients admittedthat they might not completely comprehend thescope and consequences of pharmacogenetictesting. As all patients gave written consent toparticipate in a pharmacogenetic study, it isremarkable that many patients stated limitedunderstanding later on. This knowledge gapemphasizes the importance of future patienteducation in research and routine practice [8].

Female patients were more likely to have con-cerns regarding possible negative consequencesof pharmacogenetic testing; and youngerpatients were more likely to be optimistic thatpharmacogenetic tests would improve treatment.

This partly agrees with studies demonstratingthat older people are in general more anxiousabout genetic testing [29]. Such patients presuma-bly have had the experience that the selection ofa medication was the result of trial and error,rather then via directed (pharmacogenetic) test-ing. In contrast, younger patients obviously hopeto accelerate the choice of medication usingpharmacogenetic procedures and may be moreaccepting of technological progress [34]. It isinteresting that education and the perceivedseverity of illness, as assessed by a quality of lifemeasure, did not influence patient attitudetoward pharmacogenetic testing.

The GPs’ perspectiveThe GPs were more reserved toward pharmaco-genetic testing than patients. This attitude is inline with the finding that merely describing atest as genetic (in contrast to a serum protein-based test) results in an 11% reduction in phy-sicians’ adoption of such tools, such as for thechoice of the right drug for smoking cessation[35,36]. Indeed, pharmacogenetic tests are clini-cally performed to a lesser degree than expected[37]. Possible reasons for this reservation can beinferred from studies regarding predictivegenetic testing that indicate that GPs worryabout being confronted with a ‘therapeutic gap’– in possession of genetic information but withno treatment option [38,39]. Also, experts fromEurope and North America, such as academicsand consumer representatives, appeal for a pro-found evaluation of the utility of pharmaco-genetic tests in clinical decision making prior to

Table 2. Predictors for a fearful attitude of physicians toward pharmacogenetic testing.

Predictors Prevalence N(%)

OR 95% CI p-value

Age (years)

<50 37 (71.15) 1

>50 40 (74.07) 1.16 0.49–2.72 0.74

Gender

Female 19 (70.37) 1

Male 58 (73.42) 1.16 0.44–3.05 0.76

Place of residence

Urban 36 (65.45) 1

Rural 41 (80.39) 2.16 0.89–5.25 0.09

Size of practice

<median 41 (70.69) 1

>median 36 (75.00) 1.24 0.52–2.95 0.62

CI: Confidence interval; N: Number; OR: Odds ratio.

57

RESEARCH REPORT – Rogausch, Prause, Schallenberg, Brockmöller & Himmel

58

Highlights

• Patients’ and physiciaessential for its integr

• Patients who took patoward possible beneregard to their own u

• More than half of thepharmacogenetic advprivacy not be protectfor example, with an

• Half of the participatipharmacogenetic testvoiced greater concerunder pressure to agr

• Results of this survey the hopes and worrie

their integration into routine practice [40].However, GPs seem to balance the risk of dis-crimination, economic cost and possible dis-advantages at health insurance agencies [41]

against positive reasons for testing [42]. In a fur-ther study using open questions we aim to ana-lyze in more depth the physicians’ personalmotives behind their rather reserved attitude,and in particular aim to elucidate how this isinfluenced by the specific properties andindications of a pharmacogenetic test.

GPs in our study seemed to be more open-minded toward basic pharmacogenetic researchthan routine pharmacogenetic testing. This read-iness to support research corresponds with the

attitudes of the lay public [43]. Approximately80% of the GPs thought that informed consentprior to a pharmacogenetic test was indispensa-ble. Whether this conviction will be reflected infuture medical routine is not yet clear [44]. There-fore, the results presented in this paper may beinteresting not only for the future of pharmaco-genetic and genomic testing in general medicalpractice, but also for all those who are currentlyperforming pharmacogenetic studies.

Conclusion & outlookImplementation of pharmacogenetic testing intoroutine care will pose new challenges to patientsand the GPs who have to decide on the applica-tion of these tests [45]. If prospective, randomizedcontrolled trials establish pharmacogenetic test-ing to be cost-effective in primary care [46–48],patients’ and physicians’ worries have to beaddressed. Development of information for phy-sicians and patients would be helpful inpreventing unrealistic hopes and fears.

AcknowledgmentsThe authors wish to thank Claudia Wiesemann and Wolf-gang Poser, University of Göttingen, for valuable com-ments on the questionnaires, as well as the threeanonymous reviewers for helpful suggestions on the manu-script. We are also much obliged to all participatingpatients and physicians. Funding: The study was sup-ported by a grant from the German Ministry of Educationand Research (01GK0201).

ns’ acceptance of pharmacogenetic testing is ation into routine medical practice.rt in a pharmacogenetic study were enthusiastic fits of pharmacogenetic testing, but skeptical with nderstanding of test implications. patients would take a drug against ice if no alternative medication was available. Should ed, many patients expected personal disadvantages, application for employment.ng general practitioners would recommend a before administering an anti-asthma drug. They ns than patients – fearing that patients might be put ee to pharmacogenetic testing.can provide an informative basis when addressing s of patients and physicians in the future.

BibliographyPapers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.1. Johnson JA, Lima JJ: Drug receptor/effector

polymorphisms and pharmacogenetics: current status and challenges. Pharmacogenetics 13, 525–534 (2003).

2. Evans WE, McLeod HL: Pharmacogenomics – drug disposition, drug targets, and side effects. N. Engl. J. Med. 348(6), 538–549 (2003).

3. Srivastava P: Drug metabolism and individualized medicine. Curr. Drug. Metab. 4(1), 33–44 (2003).

4. Schaeffeler E, Fischer C, Brockmeier D et al.: Comprehensive analysis of thiopurine S-methyltransferase phenotype–genotype correlation in a large population of German–Caucasians and identification of novel TPMT variants. Pharmacogenetics 14(7), 407–417 (2004).

5. Williams-Jones B, Corrigan OP: Rhetoric and hype: where's the 'ethics' in

pharmacogenomics? Am. J. Pharmacogenomics 3(6), 375–383 (2003).

6. Nebert DW, Jorge-Nebert L, Vesell ES: Pharmacogenomics and "individualized drug therapy": high expectations and disappointing achievements. Am. J. Pharmacogenomics 3(6), 361–370 (2003).

7. Goldstein DB: Pharmacogenetics in the laboratory and the clinic. N. Engl. J. Med. 348(6), 553–556 (2003).

8. Emery J, Hayflick S: The challenge of integrating genetic medicine into primary care. BMJ 322(7293), 1027–1030 (2001).

9. Wolf CR, Smith G, Smith RL: Science, medicine, and the future: pharmacogenetics. BMJ 320(7240), 987–990 (2000).

10. Issa AM: Ethical perspectives on pharmacogenomic profiling in the drug development process. Nature Rev. Drug. Discov. 1(4), 300–308 (2002).

11. Thomas SM: Pharmacogenetics: the ethical context. Pharmacogenomics J. 1(4), 239–242 (2001).

12. Emilien G, Ponchon M, Caldas C, Isacson O, Maloteaux J-M: Impact of genomics on drug discovery and clinical medicine. QJM 93(7), 391–423 (2000).

13. Issa AM: Ethical considerations in clinical pharmacogenomics research. Trends Pharmacol. Sci. 21(7), 247–249 (2000).

14. March R, Cheeseman K, Doherty M: Pharmacogenetics – legal, ethical and regulatory considerations. Pharmacogenomics 2(4), 317–327 (2001).

15. Nebert DW, Bingham E: Pharmacogenomics: out of the lab and into the community. Trends Biotechnol. 19(12), 519–523 (2001).

16. Lindpaintner K: Pharmacogenetics and the future of medical practice. Br. J. Clin. Pharmacol. 54(2), 221–230 (2002).

17. Green MJ, Botkin JR: "Genetic exceptionalism" in medicine: clarifying the differences between genetic and nongenetic tests. Ann. Intern. Med. 138(7), 571–575 (2003).

Pharmacogenomics (2006) 7(1)

Patients’ and physicians’ perspectives on pharmacogenetic testing – RESEARCH REPORT

18. Vaszar LT, Rosen GD, Raffin TA: Pharmacogenomics and the challenge to privacy. Pharmacogenomics J. 2(3), 144–147 (2002).

19. Moldrup C: Ethical, social and legal implications of pharmacogenomics: a critical review. Community Genet. 4(4), 204–214 (2002).

•• Excellent review of the ethical issues of pharmacogenetics and how they affect individuals, groups, industry and society.

20. Fears R, Roberts D, Poste G: Rational or rationed medicine? The promise of genetics for improved clinical practice. BMJ 320(7239), 933–935 (2000).

21. Weinshilboum R, Wang L: Pharmacogenomics – bench to bedside. Nature Rev. Drug Discov. 3(9), 739–748 (2004).

22. Rogausch A, Brockmöller J, Himmel W: Pharmacogenetics in future medical care – implications for patients and physicians (in German) Gesundheitswesen 67(4), 257–263 (2005).

23. Jones P, Quirk FH, Baveystock CM: The St George's Respiratory Questionnaire. Respir. Med. 85(Suppl. B), 25–31 (1991).

24. Wetzel D, Himmel W, Heidenreich R et al.: Participation in a quality of care study and consequences for generalizability of general practice research. Fam. Pract. 22(4), 458–464 (2005).

25. Lichter JB, Kurth JH: The impact of pharmacogenetics on the future of healthcare. Curr. Opin. Biotechnol. 8(6), 692–695 (1997).

26. Wechsler ME, Israel E: How pharmacogenomics will play a role in the management of asthma. Am. J. Respir. Crit. Care Med. 172(1), 12–18 (2005).

27. Bevan JL, Lynch JA, Dubriwny TN et al.: Informed lay preferences for delivery of racially varied pharmacogenomics. Genet. Med. 5(5), 393–399 (2003).

28. Jallinoja P, Hakonen A, Aro A et al.: Attitudes towards genetic testing: analysis of contradictions. Soc. Sci. Med. 46(10), 1367–1374 (1998).

29. Berth H, Balck F, Dinkel A: Attitudes toward genetic testing in patients at risk for

HNPCC/FAP and the German population. Genet Test. 6(4), 273–280 (2002).

30. Almarsdottir AB, Bjornsdottir I, Traulsen JM: A lay prescription for tailor-made drugs – focus group reflections on pharmacogenomics. Health Policy 71(2), 233–241 (2005).

31. Ingelman-Sundberg M: Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J. Intern. Med. 250(3), 186–200 (2001).

32. Schmedders M, van Aken J, Feuerstein G, Kollek R: Individualized pharmacogenetic therapy: a critical analysis. Community Genet. 6(2), 114–119 (2003).

33. Emery J: Is informed choice in genetic testing a different breed of informed decision-making? A discussion paper. Health Expect. 4(2), 81–86 (2001).

34. Henneman L, Timmermans DR, van der Wal G: Public experiences, knowledge and expectations about medical genetics and the use of genetic information. Community Genet. 7(1), 33–43 (2004).

35. Shields AE, Blumenthal D, Weiss KB, Comstock CB, Currivan D, Lerman C: Barriers to translating emerging genetic research on smoking into clinical practice. Perspectives of primary care physicians. J. Gen. Intern. Med. 20(2), 131–138 (2005).

36. Stamp MJ, David SP: Are family physicians willing to use pharmacogenetics for smoking cessation therapy? Fam. Med. 35(2), 83 (2003).

37. Gardiner SJ, Begg EJ: Pharmacogenetic testing for drug metabolizing enzymes: is it happening in practice? Pharmacogenet. Genomics 15(5), 365–369 (2005).

38. Kumar S, Gantley M: Tensions between policy makers and general practitioners in implementing new genetics: grounded theory interview study. BMJ 319(7222), 1410–1413 (1999).

39. Robins R, Metcalfe S: Integrating genetics as practices of primary care. Soc. Sci. Med. 59(2), 223–233 (2004).

40. Melzer D, Detmer D, Zimmern R: Pharmacogenetics and public policy: expert views in Europe and North America. Pharmacogenomics 4(6), 689–691 (2003).

41. McCann S, Macauley D, Barnett Y: Genetic consultations in primary care: GPs’ responses to three scenarios. Scand. J. Prim. Health Care. 23(2), 109–114 (2005).

42. Mountcastle-Shah E, Holtzman NA: Primary care physicians' perceptions of barriers to genetic testing and their willingness to participate in research. Am. J. Med. Genet. 94(5), 409–416 (2000).

•• Qualitative study providing an insight into general practitioners’ concerns related to the integration of genetic services into routine care.

43. Rothstein MA & Hornung CA: Public attitudes about pharmacogenomics. In: Pharmacogenomics. Social, ethical, and clinical dimensions. Rothstein MA (Ed.), John Wiley, New Jersey, USA, 3–27 (2003).

•• One of the few empirical studies about the public acceptance of pharmacogenetics.

44. Hedgecoe A: At the point at which you can do something about it, then it becomes more relevant: informed consent in the pharmacogenetic clinic. Soc. Sci. Med. 61(6), 1201–1210 (2005).

45. van Delden J, Bolt I, Kalis A, Derijks J, Leufkens H: Tailor-made pharmacotherapy: future developments and ethical challenges in the field of pharmacogenomics. Bioethics 18(4), 303–321 (2004).

46. Kirchheiner J, Fuhr U, Brockmöller J: Pharmacogenetics-based therapeutic recommendations – ready for clinical practice? Nature Rev. Drug Discov. 4(8), 639–647 (2005).

47. Freund CL, Wilfond BS: Emerging ethical issues in pharmacogenomics: from research to clinical practice. Am. J. Pharmacogenomics 2(4), 273–281 (2002).

48. Knottnerus JA, van Weel C, Muris JW: Evaluation of diagnostic procedures. Br. Med. J. 324, 477–480 (2002).

Website101. KBV website.

www.kbv.de

www.futuremedicine.com 59