Subjective Reasons for Non-Reporting of Adverse Drug Reactions in a Sample of Physicians in Outpatient Care

• Abstract
• Introduction
• Materials and Methods
• Study design
• Study population
• Survey and data collection
• Questionnaire
• Data analysis
• Results
• Discussion
• General considerations
• Reporting frequency
• Subjective reasons for non-reporting of ADRs
• Limitations
• Conclusions
• References

Abstract

Introduction: Drug safety surveillance strongly depends on the spontaneous reporting of adverse drug reactions (ADRs). A major limiting factor of spontaneous reporting systems is underreporting (UR) which describes incorrectly low reporting rates of ADRs. Factors contributing to UR are numerous and feature country-dependent differences. Understanding causes of and factors associated with UR is necessary to facilitate targeted interventions to improve ADR reporting and pharmacovigilance.

Methods: A cross-sectional questionnaire-based telephone survey was performed among physicians in outpatient care in a federal state of Germany.

Results: From n=316 eligible physicians n=176 completed the questionnaire (response rate=55.7%). Most of the physicians (n=137/77.8%) stated that they report ADRs which they have observed to the competent authority rarely (n=59/33.5%), very rarely (n=59/33.5%) or never (n=19/10.8%); the majority (n=123/69.9%) had not reported any ADRs in 2014. Frequent subjective reasons for non-reporting of ADR were (specified response options): lack of time (n=52/29.5%), the subjective evaluation that the required process of reporting is complicated (n=47/26.7%) or requires too much time (n=25/14.2%) or the assessment that reporting of an ADR is needless (n=22/12.5%); within open answers the participants frequently stated that they do not report ADRs that are already known (n=72/40.9%) and they only report severe ADRs (n=46/26.1%).

Discussion: Our results suggest a need to inform physicians about pharmacovigilance and to modify the required procedure of ADR reporting or to offer other reporting options.

Introduction

Drug safety surveillance strongly relies on spontaneous reporting of adverse drug reactions (ADRs) [1] and thus depends on the personal motivation of e. g., practising physicians to report observed ADRs. Incorrectly low reporting rates of ADRs are referred to by the term underreporting [2] which is one of the major limiting factors of spontaneous reporting systems and a challenge in pharmacovigilance [3] [4]. According to previous studies several factors contribute to underreporting of ADRs, such as a lack of knowledge about pharmacovigilance or the particular reporting system, uncertainty regarding the causal relation between the ADR and the drug, lack of time, and the belief that only serious or previously unknown ADRs should be reported [2] [5] [6] [7] [8] [9] [10] [11] [12]. Understanding the factors contributing to underreporting is necessary to develop targeted interventions to improve ADR reporting (willingness to report and quality of ADR reports) which in turn facilitates improved drug safety surveillance [13] [14] [15] [16] [17] [18].

Pharmacovigilance programs, spontaneous reporting systems, the required process of ADR reporting, health care structure, and legal framework, however, show considerable country-dependent differences [19] which, accordingly, also affect the reporting behaviour in a particular country [2]. This variability corresponds with the heterogeneity of type and impact of different determinants of underreporting between different countries [2] [9]. Therefore targeting the understanding of underreporting should primarily focus on one country or region with homogeneous reporting conditions. Regarding Germany there is only one study from the year 2002 that investigates knowledge and attitudes regarding spontaneous ADR reporting in 2 samples of German physicians [12].

In the present study we performed a cross-sectional questionnaire-based telephone survey in a sample of physicians in outpatient care in Germany to assess subjective reasons for non-reporting of observed ADRs.

Materials and Methods

Study design

A cross-sectional questionnaire-based telephone survey was conducted.

Study population

Data was obtained from a study (telephone survey; see below) on ADR related to agents frequently used in outpatient opioid maintenance therapy. Physicians who perform opioid maintenance therapy in outpatient care in Baden-Württemberg (a federal state of Germany with a population of approximately 10.7×10⁶ inhabitants in 2014) were considered for the study. Identification of these individuals was performed online in January 2015 by using a platform (www.arztsuche-bw.de) run by the association of statutory health insurance physicians of Baden-Württemberg (“Kassenärztliche Vereinigung Baden-Württemberg”).

Survey and data collection

A telephone survey among eligible physicians (see above) was performed between January and April 2015 (interviewer: JE). Identified physicians were contacted without prior notification by telephone by using publicly available business telephone numbers. Within a short introduction physicians were informed about the purpose of the survey and asked to participate. A questionnaire (see below) was completed during the telephone interview (answers were documented by the interviewer). Interviews were conducted in the German language. A drop-out was defined as rejection of participation or failed contact attempt on 3 independent days during the survey period.

Questionnaire

A standardized questionnaire (see supplemental file: English version of the questionnaire; translation by the authors) was created for the above-mentioned study including open-ended questions, multiple choice questions and questions with 7-point Likert scales (specified response options); the questionnaire was written in German language and not validated before usage. The questionnaire comprises 3 parts: (i) basic and personal data related to the interview and the respondent (time of the survey interview; age and gender of the respondent; working as a general practitioner: yes/no; title of medical specialization, if acquired), (ii) items (7 questions) regarding the reporting behaviour and ADRs related to outpatient opioid maintenance therapy (not considered for this study), and (iii) questions regarding the respondent’s reporting behaviour of ADRs in general. Before starting the third part of the questionnaire the respondent was explicitly advised that the following questions refer to her/his complete medical practice and not only to outpatient opioid maintenance therapy. The third part of the questionnaire contains 3 questions: (1) “How often do you normally report adverse drug reactions which you have observed to the competent authority?” (specified response options [7-point Likert scale]: “always”/“very often”/“often”/“occasionally”/“rarely”/“very rarely”/“never”); (2) “How many adverse drug reactions have you reported to the competent authority in 2014?” (open-ended question); (3) “When you observe an adverse drug reaction without reporting it to the competent authority: Which of the following statements are most suitable for you? [multiple answers possible]” (possibility to answer freely plus the following specified response options: “I don’t know for which cases I should report an adverse drug reaction.”/“I don’t know how to report an adverse drug reaction.”/“I don’t have time to report an adverse drug reaction”/“Reporting of an adverse drug reactions requires too much time.”/“The required process of reporting is complicated or not user-friendly.”/“I think reporting an adverse drug reaction is unnecessary.”). Translation of the above-mentioned questions from German into English was performed by the authors.

Only data related to the first and the last part of the questionnaire were used for this study.

Data analysis

Data was analysed descriptively (mean value±standard deviation [SD], median value, minimum/maximum value). Answers to the open-ended questions were assessed for similar semantic content/statements allowing for creating separate response categories; similar answers were then grouped in these categories.

Results

A total of n=316 physicians eligible to participate were identified. 176 (n=176) physicians completed the questionnaire during the telephone interview, representing a response rate of 55.7%. [Table 1] displays basic characteristics of interviewed physicians. Most of the interviewed physicians were working as general practitioners (~90%) and, accordingly, most were specialized in general practice. [Tables 2] [3] display data regarding the reporting behaviour and subjective reasons for non-reporting of ADRs.

In the year 2014, 0.6 (± 1.5 SD) ADRs were reported on average (median 0; range 0 0–15) by the interviewed physicians; 123 physicians (69.9%) stated that they did not report any ADRs in the year 2014. Most of the physicians (n=137/77.8%) stated that they report ADRs to the competent authority rarely (n=59/33.5%), very rarely (n=59/33.5%) or never (n=19/10.8%). Among the specified response options, subjective reasons frequently given for non-reporting of an ADR were lack of time (n=52/29.5%), that the required reporting process is complicated (n=47/26.7%) or requires too much time (n=25/14.2%) or that reporting of an ADR is unnecessary (n=22/12.5%). Only 11 respondents (6.3%) stated that they did not know how to report an ADR. Open answers to this question were given by n=112 (63.6%) of the respondents. In response to the open-ended questions, the interviewed physicians frequently stated that they did not report ADRs that are already known (n=72/40.9%) and they only report severe ADRs (n=46/26.1%). Uncertainty concerning causality was selected by nine respondents (5.1%).

Discussion

General considerations

We achieved a response rate of 55.7%, which is typical for telephone surveys including up to 10 questions [20]. Most of the interviewed physicians were working as general practitioners and had a respective medical specialization; concerning other medical specializations, only psychiatry/neurology and internal medicine were present in the sample. Naturally, this distribution does not represent the actual distribution of medical specializations in German outpatient care (or Baden-Württemberg) [21]; this is because data was extracted from a survey of physicians who perform outpatient opioid maintenance therapy. The characteristics of the sample (regarding age, gender, and distribution of medical specializations) correspond with the characteristics of physicians who perform outpatient opioid maintenance therapy [21]. Based upon some inconsistencies between several answers (e. g., n=5 stated that they always report ADRs that they have observed vs. n=8 stated that they report all ADRs), plausibility of the given answers may be limited.

Reporting frequency

Considering that n=123 (69.9%) of the interviewed physicians did not report any ADRs in 2014 and that ADRs usually occur with remarkable frequency [22] [23], underreporting seems to be present in the analyzed sample. Accordingly, most of the respondents (n=137/77.8%) stated that they normally report ADRs rarely, very rarely or never. This is in line with findings from previous studies which have revealed similarly low ADR reporting rates [2] [5] [6] [7] [8] [9] [10] [11].

Subjective reasons for non-reporting of ADRs

Within the specified response options, frequent subjective reasons for non-reporting were lack of time (n=52/29.5%), that the required process of reporting is complicated (n=47/26.7%) or requires too much time (n=25/14.2%) or that reporting of an ADR is unnecessary (n=22/12.5%). Lack of time is a condition characterizing the physician’s working environment; the physicians’ evaluation that the required process of reporting is complicated or requires too much time is a condition presumably characterizing the subjective evaluation of the ADR reporting procedure. Both conditions together suggest that simplifying the required reporting process may reduce underreporting in Germany. Indeed, the majority (54%) of respondents of a previous survey (questionnaire-based, distribution by mail) performed in 2002 by Hasford et al. [12] among 2 different samples of German physicians (random sample and sample of physicians who have reported an ADR during a defined period of time) “asked for the possibility to report by phone to a qualified drug information service” [12]. The possibility to report by phone was also preferred by the majority of physicians in other studies [24] [25]. Moreover, the number of spontaneous ADR reports increased significantly in a study after providing the possibility to report by phone [26]. Currently, reporting of ADRs in Germany can be performed via mail or online. Only n=11 (6.3%) of the respondents of our study indicated that they do not know how to report an ADR, suggesting that physicians are aware of the correct process of ADR reporting, however do not know which ADRs should be reported. Finally, taking into account that a considerable number of participants (n=22/12.5%) do not report ADRs because they believe that ADR reporting is unnecessary, lack of knowledge concerning the importance of drug safety seems to play a role.

Within the open answers physicians frequently stated that they do not report already known ADRs (n=72/40.9%) or only report serious ADRs (n=46/26.1%), which corresponds with findings of several previous studies [2] [5] [6] [7] [8] [9] [10] [11]. Hasford et al. found that most of the participants of both samples do not report an ADR when the respective ADR was “too well known” or “too trivial” [12]. This is in line with the results of our study from the responses to the open-ended questions: apparently, many physicians from our sample only report an ADR when they believe it is not yet known or severe. In Germany physicians are obliged by the German Medical Association’s code of conduct (not by law) to report ADRs including suspected ADRs which are observed during their medical practice; ADRs should be reported to the responsible authority independently of their kind, severity and regardless of whether the respective ADR is known or not [27] (due to possible inter-individual differences concerning the assessment of ADRs); this is also supported by the German Pharmaceutical Drug Law (Arzneimittelgesetz; see http://www.gesetze-im-internet.de/amg_1976/index.html). Although we did not explicitly assess the physicians’ knowledge regarding pharmacovigilance/ADR reporting, results from the answers from our survey indirectly suggest that the physicians have insufficient knowledge concerning the appropriate reporting behaviour in Germany; this assumption is also supported by the conflicting finding that only 14 respondents (8.0%) indicated that they do not know in which cases they should report an ADR vs. 72 participants (40.9%) stating that they do not report already known ADRs and 46 (26.1%) stating that they only report severe ADRs. Significant lack of knowledge concerning appropriate ADR reporting and/or pharmacovigilance was also demonstrated by the study of Hasford et al. [12] for 2 samples of German physicians and in several other studies [8]. Furthermore, it was shown that lack of knowledge concerning the ADR reporting system is a major cause of underreporting [8]. In contrast to the study by Hasford et al. which found that doubt about causality between drug and ADR was stated by about 2 thirds of participants in case of non-reporting of an ADR, in our study only 9 physicians (5.1%) provided this reason. This may be due to increased general awareness concerning the importance of drug safety, probably as a consequence of the latest amendments to the Medicines Act of the Federal Republic of Germany (“Arzneimittelgesetz” – AMG) from the year 2004 on (12^th amendment to the AMG) which successively strengthened the role of pharmacovigilance by several new directives for the pharmaceutical industry and the reporting physician.

Limitations

Major drawbacks of our study are moderate sample size, absent validation of the used questionnaire and absent representativeness of the sample. Thus there is uncertainty if the applied questions were comprehensible for the interviewed physicians and appropriate to evaluate physicians’ ADR reporting behaviour. In addition, our findings are not generalisable and are valid at the utmost for outpatient physicians of a federal state of Germany who perform outpatient opioid maintenance therapy. Moreover, we did not explicitly examine the knowledge of the interviewed physicians regarding the possible ways of reporting ADRs in Germany and aspects of pharmacovigilance (definition of an ADR), but rather presupposed sufficient knowledge concerning possibilities of ADR reporting and key terms (e. g., using the term “competent authority” without further elucidation and presupposing that the respondents know that this term may denote the Federal Institute for Drugs and Medical Devices [Bundesinstitut für Arzneimittel und Medizinprodukte – BfArM] or the Drug Commission of the German Medical Association [Arzneimittelkommission der Deutschen Ärzteschaft – AkdÄ]; these institutions jointly run an ADR database and the national spontaneous ADR reporting system). Thus it is possible that during the interview some physicians have intentionally disregarded other possibilities of ADR reporting in Germany as e. g., ADR reporting to representatives of the pharmaceutical industry (in Germany sales representatives are obliged to document and transmit every suspected ADR communicated by a physician [12]). For the present evaluation we used data originating from a survey primarily addressing physicians who perform outpatient opioid maintenance therapy; this selectivity has induced a bias which has to be considered when interpreting our results.

Conclusions

The results of a telephone survey among German outpatient physicians suggest that the lack of time associated with medical practice together with the physicians’ evaluation that the required process of ADR reporting is unnecessarily time-consuming and complicated may be relevant subjective reasons for underreporting. Therefore modifications of the required reporting procedure (simplification and offering other reporting options) may reduce underreporting. Furthermore, our results indirectly suggest a lack of knowledge regarding the importance of drug safety surveillance and/or the German pharmacovigilance system, particularly concerning the appropriate ADR reporting. Considering that lack of knowledge is a major factor contributing to underreporting, interventions in order to inform physicians about pharmacovigilance are needed.

Conflict of Interest

The authors declare no conflict of interest.

• References

• 1 Borg J, Aislaintner G, Pirozynski M et al. Strengthening and rationalizing pharmacovigilance in the EU: where is Europe heading to? A review of the new EU legislation on pharmacovigilance. Drug Saf 2011; 34: 187-197
  CrossrefPubMedSearch in Google Scholar
• 2 Hazell L, Shakir S. Under-reporting of adverse drug reactions: a systematic review. Drug Saf 2006; 29: 385-396
  CrossrefPubMedSearch in Google Scholar
• 3 Pushkin R, Frasetto L, Tsourounis C et al. Improving the reporting of adverse drug reactions in the hospital setting. Postgrad Med 2010; 122: 154-164
  CrossrefPubMedSearch in Google Scholar
• 4 Martin R, Kapoor K, Wilton L et al. Underreporting of suspected adverse drug reactions to newly marketed (“black triangle”) drugs in general practice: observational study. BMJ 1998; 317: 119-120
  CrossrefPubMedSearch in Google Scholar
• 5 Irujo M, Beitia G, Bes-Rastrollo M et al. Factors that influence under-reporting of suspected adverse drug reactions among community pharmacists in a Spanish region. Drug Saf 2007; 30: 1073-1082
  CrossrefPubMedSearch in Google Scholar
• 6 Khan S, Goval C, Chandel N et al. Knowledge, attitudes, and practice of doctors to adverse drug reaction reporting in a teaching hospital in India: An observational study. J Nat Sci Biol Med 2013; 4: 191-196
  CrossrefPubMedSearch in Google Scholar
• 7 Santosh K, Tragulpiankit P, Edwards I et al. Knowledge about adverse drug reactions reporting among healthcare professionals in Nepal. Int J Risk Saf Med 2013; 25: 1-16
  PubMedSearch in Google Scholar
• 8 Pérez García M, Figueras A. The lack of knowledge about the voluntary reporting system of adverse drug reactions as a major cause of underreporting: direct survey among health professionals. Pharmacoepidemiol Drug Saf 2011; 20: 1295-1302
  CrossrefPubMedSearch in Google Scholar
• 9 Lopez-Gonzalez E, Herdeiro M, Figueiras A. Determinants of under-reporting of adverse drug reactions: a systematic review. Drug Saf 2009; 32: 19-31
  CrossrefPubMedSearch in Google Scholar
• 10 Tandon V, Mahajan V, Khajuria V et al. Under-reporting of adverse drug reactions: a challenge for pharmacovigilance in India. Indian J Pharmacol 2015; 47: 65-71
  CrossrefPubMedSearch in Google Scholar
• 11 dos Santos Pernas S, Herdeiro M, Lopez-Gonzalez E et al. Attitudes of Portuguese health professionals towards adverse drug reaction reporting. Int J Clin Pharmacol 2012; 34: 693-698
  CrossrefPubMedSearch in Google Scholar
• 12 Hasford J, Goettler M, Munter K et al. Physicians’ knowledge and attitudes regarding the spontaneous reporting system for adverse drug reactions. J Clin Epidemiol 2002; 55: 945-950
  CrossrefPubMedSearch in Google Scholar
• 13 Biagi C, Montanaro N, Buccellato E et al. Underreporting in pharmacovigilance: an intervention for Italians (Emilia-Romagna region). Eur J Clin Pharmacol 2013; 69: 237-244
  CrossrefPubMedSearch in Google Scholar
• 14 Herdeiro M, Ribeiro-Vaz I, Ferreira M et al. Workshop- and telephone-based interventions to improve adverse drug reaction reporting: a cluster-randomized trial in Portugal. Drug Saf 2012; 35: 655-665
  CrossrefPubMedSearch in Google Scholar
• 15 Gonzalez-Gonzalez C, Lopez-Gonzalez E, Herdeiro M et al. Strategies to improve adverse drug reaction reporting: a critical and systematic review. Drug Saf 2013; 36: 317-328
  CrossrefPubMedSearch in Google Scholar
• 16 Pagotto C, Varallo F, Mastroianni P. Impact of educational interventions on adverse drug event reporting. Int J Technol Assess Health Care 2013; 29: 410-417
  CrossrefPubMedSearch in Google Scholar
• 17 Orsini M, Orsini P, Thorn D et al. An ADR surveillance program: increasing quality, number of incidence reports. Formulary 1995; 30: 454-461
  PubMedSearch in Google Scholar
• 18 Scott H, Thacher-Renshaw A, Rosenbaum S et al. Physician reporting of adverse drug reactions. Results of the Rhode Island Adverse Drug Reaction Reporting Project. JAMA 1990; 263: 1785-1788
  CrossrefPubMedSearch in Google Scholar
• 19 Wiktorowicz M, Lexchin J, Moscou K. Pharmacovigilance in Europe and North America: divergent approaches. Soc Sci Med 2012; 75: 165-170
  CrossrefPubMedSearch in Google Scholar
• 20 Kempf A, Remington P. New challenges for telephone survey research in the twenty-first century. Annu Rev Public Health 2007; 28: 113-126
  CrossrefPubMedSearch in Google Scholar
• 21 Bundesministerium für Gesundheit. Daten des Gesundheitswesen. 2013
  PubMedSearch in Google Scholar
• 22 Muehlberger N, Schneeweiss S, Hasford J. Adverse drug reactions monitoring–cost and benefit considerations. Part I: frequency of adverse drug reactions causing hospital admissions. Pharmacoepidemiol Drug Saf 1997; 6 (Suppl. 03) S71-S77
  CrossrefPubMedSearch in Google Scholar
• 23 Miguel A, Azevedo L, Araújo M et al. Frequency of adverse drug reactions in hospitalized patients: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2012; 21: 1139-1154
  CrossrefPubMedSearch in Google Scholar
• 24 Fincham J. Pilot projects to stimulate adverse drug reaction reporting. J Clin Pharm Ther 1987; 12: 243-247
  CrossrefPubMedSearch in Google Scholar
• 25 Robins A, Weir M, Biersteker E. Attitudes to adverse drug reactions and their reporting among medical practitioners. S Afr Med J 1987; 72: 131-134
  PubMedSearch in Google Scholar
• 26 Rogers A, Israel E, Smith C et al. Physician knowledge, attitudes, and behavior related to reporting adverse drug events. Arch Intern Med 1988; 148: 1596-1600
  CrossrefPubMedSearch in Google Scholar
• 27 Bundesärztekammer. (Muster-) Berufsordnung für die in Deutschland tätigen Ärztinnen und Ärzte – MBO-Ä 1997 – in der Fassung des Beschlusses des 118. Deutschen Ärztetages 2015 in Frankfurt am Main. 2015
  PubMedSearch in Google Scholar

Correspondence

• References

• 1 Borg J, Aislaintner G, Pirozynski M et al. Strengthening and rationalizing pharmacovigilance in the EU: where is Europe heading to? A review of the new EU legislation on pharmacovigilance. Drug Saf 2011; 34: 187-197
  CrossrefPubMedSearch in Google Scholar
• 2 Hazell L, Shakir S. Under-reporting of adverse drug reactions: a systematic review. Drug Saf 2006; 29: 385-396
  CrossrefPubMedSearch in Google Scholar
• 3 Pushkin R, Frasetto L, Tsourounis C et al. Improving the reporting of adverse drug reactions in the hospital setting. Postgrad Med 2010; 122: 154-164
  CrossrefPubMedSearch in Google Scholar
• 4 Martin R, Kapoor K, Wilton L et al. Underreporting of suspected adverse drug reactions to newly marketed (“black triangle”) drugs in general practice: observational study. BMJ 1998; 317: 119-120
  CrossrefPubMedSearch in Google Scholar
• 5 Irujo M, Beitia G, Bes-Rastrollo M et al. Factors that influence under-reporting of suspected adverse drug reactions among community pharmacists in a Spanish region. Drug Saf 2007; 30: 1073-1082
  CrossrefPubMedSearch in Google Scholar
• 6 Khan S, Goval C, Chandel N et al. Knowledge, attitudes, and practice of doctors to adverse drug reaction reporting in a teaching hospital in India: An observational study. J Nat Sci Biol Med 2013; 4: 191-196
  CrossrefPubMedSearch in Google Scholar
• 7 Santosh K, Tragulpiankit P, Edwards I et al. Knowledge about adverse drug reactions reporting among healthcare professionals in Nepal. Int J Risk Saf Med 2013; 25: 1-16
  PubMedSearch in Google Scholar
• 8 Pérez García M, Figueras A. The lack of knowledge about the voluntary reporting system of adverse drug reactions as a major cause of underreporting: direct survey among health professionals. Pharmacoepidemiol Drug Saf 2011; 20: 1295-1302
  CrossrefPubMedSearch in Google Scholar
• 9 Lopez-Gonzalez E, Herdeiro M, Figueiras A. Determinants of under-reporting of adverse drug reactions: a systematic review. Drug Saf 2009; 32: 19-31
  CrossrefPubMedSearch in Google Scholar
• 10 Tandon V, Mahajan V, Khajuria V et al. Under-reporting of adverse drug reactions: a challenge for pharmacovigilance in India. Indian J Pharmacol 2015; 47: 65-71
  CrossrefPubMedSearch in Google Scholar
• 11 dos Santos Pernas S, Herdeiro M, Lopez-Gonzalez E et al. Attitudes of Portuguese health professionals towards adverse drug reaction reporting. Int J Clin Pharmacol 2012; 34: 693-698
  CrossrefPubMedSearch in Google Scholar
• 12 Hasford J, Goettler M, Munter K et al. Physicians’ knowledge and attitudes regarding the spontaneous reporting system for adverse drug reactions. J Clin Epidemiol 2002; 55: 945-950
  CrossrefPubMedSearch in Google Scholar
• 13 Biagi C, Montanaro N, Buccellato E et al. Underreporting in pharmacovigilance: an intervention for Italians (Emilia-Romagna region). Eur J Clin Pharmacol 2013; 69: 237-244
  CrossrefPubMedSearch in Google Scholar
• 14 Herdeiro M, Ribeiro-Vaz I, Ferreira M et al. Workshop- and telephone-based interventions to improve adverse drug reaction reporting: a cluster-randomized trial in Portugal. Drug Saf 2012; 35: 655-665
  CrossrefPubMedSearch in Google Scholar
• 15 Gonzalez-Gonzalez C, Lopez-Gonzalez E, Herdeiro M et al. Strategies to improve adverse drug reaction reporting: a critical and systematic review. Drug Saf 2013; 36: 317-328
  CrossrefPubMedSearch in Google Scholar
• 16 Pagotto C, Varallo F, Mastroianni P. Impact of educational interventions on adverse drug event reporting. Int J Technol Assess Health Care 2013; 29: 410-417
  CrossrefPubMedSearch in Google Scholar
• 17 Orsini M, Orsini P, Thorn D et al. An ADR surveillance program: increasing quality, number of incidence reports. Formulary 1995; 30: 454-461
  PubMedSearch in Google Scholar
• 18 Scott H, Thacher-Renshaw A, Rosenbaum S et al. Physician reporting of adverse drug reactions. Results of the Rhode Island Adverse Drug Reaction Reporting Project. JAMA 1990; 263: 1785-1788
  CrossrefPubMedSearch in Google Scholar
• 19 Wiktorowicz M, Lexchin J, Moscou K. Pharmacovigilance in Europe and North America: divergent approaches. Soc Sci Med 2012; 75: 165-170
  CrossrefPubMedSearch in Google Scholar
• 20 Kempf A, Remington P. New challenges for telephone survey research in the twenty-first century. Annu Rev Public Health 2007; 28: 113-126
  CrossrefPubMedSearch in Google Scholar
• 21 Bundesministerium für Gesundheit. Daten des Gesundheitswesen. 2013
  PubMedSearch in Google Scholar
• 22 Muehlberger N, Schneeweiss S, Hasford J. Adverse drug reactions monitoring–cost and benefit considerations. Part I: frequency of adverse drug reactions causing hospital admissions. Pharmacoepidemiol Drug Saf 1997; 6 (Suppl. 03) S71-S77
  CrossrefPubMedSearch in Google Scholar
• 23 Miguel A, Azevedo L, Araújo M et al. Frequency of adverse drug reactions in hospitalized patients: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2012; 21: 1139-1154
  CrossrefPubMedSearch in Google Scholar
• 24 Fincham J. Pilot projects to stimulate adverse drug reaction reporting. J Clin Pharm Ther 1987; 12: 243-247
  CrossrefPubMedSearch in Google Scholar
• 25 Robins A, Weir M, Biersteker E. Attitudes to adverse drug reactions and their reporting among medical practitioners. S Afr Med J 1987; 72: 131-134
  PubMedSearch in Google Scholar
• 26 Rogers A, Israel E, Smith C et al. Physician knowledge, attitudes, and behavior related to reporting adverse drug events. Arch Intern Med 1988; 148: 1596-1600
  CrossrefPubMedSearch in Google Scholar
• 27 Bundesärztekammer. (Muster-) Berufsordnung für die in Deutschland tätigen Ärztinnen und Ärzte – MBO-Ä 1997 – in der Fassung des Beschlusses des 118. Deutschen Ärztetages 2015 in Frankfurt am Main. 2015
  PubMedSearch in Google Scholar

• Supplementary Material