Quality check of spontaneous adverse drug reaction reporting forms of different countries y

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1 pharmacoepidemiology and drug safety (2010) Published online in Wiley Online Library (wileyonlinelibrary.com).2004 ORIGINAL REPORT Quality check of spontaneous adverse drug reaction reporting forms of different countries y M. S. Bandekar, S. R. Anwikar and N. A. Kshirsagar*,z Department of Infectious Diseases and Department of Interdisciplinary Research and Technology, Maharashtra University of Health Sciences, Maharashtra, India SUMMARY Adverse drug reactions (ADRs) are considered as one of the leading causes of death among hospitalized patients. Thus reporting of adverse drug reactions become an important phenomenon. Spontaneous adverse drug reaction reporting form is an essential component and a major tool of the pharmacovigilance system of any country. This form is a tool to collect information of ADRs which helps in establishing the causal relationship between the suspected drug and the reaction. As different countries have different forms, our aim was to study, analyze the suspected adverse drug reaction reporting form of different countries, and assess if these forms can capture all the data regarding the adverse drug reaction. For this analysis we identified 18 points which are essential to make a good adverse drug reaction report, enabling proper causality assessment of adverse reaction to generate a safety signal. Adverse drug reaction reporting forms of 10 different countries were collected from the internet and compared for 18 points like patient information, information about dechallenge rechallenge, adequacy of space and columns to capture necessary information required for its causality assessment, etc. Of the ADR forms that we analyzed, Malaysia was the highest scorer with 16 out of 18 points. This study reveals that there is a need to harmonize the ADR reporting forms of all the countries because there is a lot of discrepancy in data captured by the existing ADR reporting forms as the design of these forms is different for different countries. These incomplete data obtained result in inappropriate causality assessment. Copyright # 2010 John Wiley & Sons, Ltd. key words pharmacovigilance; spontaneous ADR reporting forms; adverse drug reactions Received 22 March 2010; Revised 7 April 2010; Accepted 22 May 2010 INTRODUCTION Adverse drug reactions are considered as one of the leading causes of death among hospitalized patients. 1 They are defined as a noxious, unintended effect of a drug, occurring at normal doses in humans for prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function. 2 Information about adverse drug reactions (ADRs) can be obtained through data from preclinical studies and * Correspondence to: N. A. Kshirsagar, Department of Infectious Diseases and Department of Interdisciplinary Research and Technology, Maharashtra University of Health Sciences, Maharashtra, India. kshirsagarna@yahoo.in y Authors declare no conflict of interest. z Director of Department of Infectious Diseases and Department of Interdisciplinary Research and Technology, Maharashtra University of Health Sciences, Maharashtra, India. Emeritus Professor in Department of Clinical Pharmacology, Seth GS Medical College and King Edward Memorial Hospital, Acharya Donde Marg, Parel, Mumbai, India. clinical trials but rare adverse reactions, which occur only in a small percentage of cases, after a long period of drug use or drug interactions with other established s may not be detected during clinical trials. For ADRs not discovered during clinical trials to be detected, investigated and communicated, there is a need for an extensive post-marketing pharmacovigilance of all medicines. The responsibility of any drug authority is to ensure the safety, efficacy, and quality of all marketed products. Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other medicine-related problem. 3 Pharmacovigilance can be done by various methods like cohort studies, prescription event monitoring, etc. but spontaneous ADR reporting is a widely used method of pharmacovigilance. It is used to generate hypotheses and signals about potential hazards of Copyright # 2010 John Wiley & Sons, Ltd.

2 marketed that require further investigation. Spontaneous reporting of suspected ADRs is particularly useful in identifying rare or delayed reactions, as such a system enables medicines to be monitored throughout their lifetime. 4 Most of the countries have National Pharmacovigilance program center/s or unit/s which carry out the adverse drug reaction monitoring. These centers are mainly concerned with the collection of spontaneous and suspected ADR reports, carry out causality assessment, and submit to regulatory authority. The reports are then sent to the WHO s ADR Monitoring Center at Uppsala, Sweden where this information is pooled and unexpected reactions are watched for when data mining methods are used; also suspected ADRs are sent out as signals to the national pharmacovigilance centers. Spontaneous adverse drug reaction reporting form is an essential component and a major tool of the pharmacovigilance system of any country. This form is a tool to collect information of ADRs which helps in establishing the causal relationship between the suspected drug and the reaction. If relevant information regarding ADR is not adequately captured then it is of no use for the regulatory authority as no conclusion can be drawn from those data. Every country has developed its own spontaneous ADR reporting form for data collection which is used by them to capture information about an adverse event. The newsletter of WHO Pharmaceuticals has also cited the need for a generic form for spontaneous reporting of adverse drug reactions. 4 As different countries have different forms, our aim was to study, analyze the suspected adverse drug reaction reporting form of different countries, and assess if the forms can capture all the data regarding the adverse drug reaction. For this analysis, we identified 18 points which are essential to make a good adverse drug reaction report enabling proper causality assessment of adverse reaction to generate a safety signal. The characteristics of good case report include details about patient information, description of adverse event, temporal relationship drug administered, use of drug, rechallenge, dechallenge, etc. METHOD Adverse drug reaction reporting forms of 10 different countries were collected from the internet and compared for 18 points like patient information, information about dechallenge rechallenge, adequacy of space and columns to capture necessary information required for its causality assessment, etc. (Table 1). m. s. bandekar ET AL. Presence of different elements is expressed as yes (H) or no(t); presence of each element is scored as one mark, absence as zero and scores are totaled. RESULTS All the ADR forms which were studied had asked for detailed patient information like age, sex and weight, list of suspected, outcome of the reaction, and also start and stop date of reaction and. The few important points that were missing from the ADR forms were information about allergic status, which was not asked for in the ADR forms of Pakistan, UK, and Kenya. Information related to pregnancy status was only asked for in the ADR forms of Pakistan and Kenya. Another most important information required for causality assessment is dechallenge which does not feature on the ADR forms of Pakistan, UK, Australia, and South Africa. Pakistan, Kenya, and Australia have not asked for information on rechallenge either (Tables 1 and 2). Of the ADR forms that we analyzed, Malaysia was the highest scorer with 16 out of 18 points. Pakistan fared below 50% on the 18-point scale, followed by Australia, South Africa, UK, India, USA, Kenya, and South Africa. DISCUSSION The different parameters that were used to study the forms were the information regarding demographic details of patients as crucial information regarding age, sex can be obtained which helps in correlation, details(author: sense not clear. Please check.) about the description of ADR helps us to get a detailed understanding of the ADR, the drug administered, s to check for any drug drug interactions, etc. Requirement of information on the prior allergic status and whether the patient is allergic to any drug is important. It should be considered because if patient has a history of allergy to a particular drug and the same drug is administered then it will affect the causality assessment of ADR resulting from such a case. Pregnancy status is an important parameter for the causality assessment of ADR in female patients. For example, if a patient had experienced nausea and vomiting, it may not be necessarily because of drug but could be because of the patient s pregnancy status. The administered dose,route and frequency are important parameters which helps us to know whether the ADR would have been caused because of incorrect dose and/or frequency for the suspected drug. In that case it could be wrongly interpreted as ADR. Also this

3 QUALITY CHECK OF ADVERSE DRUG REACTIONs Table 1. Assessment of spontaneous adverse drug reaction reporting form of different countries Contents Country India 5 Pakistan 6 USA 7 UK 8 Kenya 9 Malaysia 10 Canada 11 Australia 12 South Africa 13 Tanzania 14 Patient s information H H H H H H H H H H Pregnancy status H H Allergic status H H H H H H H Diagnosis H H H H H H H H Description of reaction H H H H H H H H H Proper space No space Proper space Proper space Less space Medium space Proper space Proper space Less space Less space List of suspected H H H H H H H H H H Very less space. Only single drug can be entered Proper space to enter more than two, Ten name can be entered Proper space to enter more than two, Six Six Dose, frequency of H H H H H H H H H space is Space for H H H H H H H H H Start date and stop date of suspected No space drug H H H H H H H H H H Date of stopping not mentioned. Duration of treatment is mentioned Relevant history of patients H H H H H H H H H Actions taken H H Severity H H H Causality H H Outcome H H H H H H H H H H Dechallenge H H H H H H Rechallenge H H H H H H H Treatment of ADR H H H H H H Lot no, expiration date H H H H H H space is, mentioned in space of suspected information Three to four

4 m. s. bandekar ET AL. Table 2. Scores of different countries Sr. No. Country Score out of 18 1 India 13 2 Pakistan 6 3 USA 13 4 UK 12 5 Kenya 13 6 Malaysia 16 7 Canada 14 8 Australia 12 9 South Africa Tanzania 14 provides us with vital information on whether errors, if so have occurred. All the countries except Pakistan had space to enter description of reaction, list of, dose, and frequency of. Relevant history of patient was mentioned in the forms of all countries except Kenya whereas the actions taken were asked only in two countries, viz. UK and Kenya. The mandatory information required for causality assessment includes information on temporal relationship, dechallenge, and rechallenge of the administered drug. Of the forms analyzed, information regarding dechallenge is not asked for in Pakistan, UK, and Australia whereas rechallenge is not mentioned in Pakistan, Kenya, and Australia. Only Kenya and Malaysia asked for causality to be written on spontaneous ADR report forms and India, Pakistan, Kenya, and USA s forms do not have separate column for treatment of ADR as mentioned in other countries. High scoring of Malaysia shows that spontaneous ADR reporting form of this country is capable of capturing maximum data about adverse drug reaction and thus this form will help to generate proper safety signals. This study reveals that there is a need to harmonize the ADR reporting forms of all the countries because there is a lot of discrepancy in data captured by the existing ADR reporting forms as the design of these forms is different for different countries. These incomplete data obtained result in inappropriate causality assessment of ADRs and possible signal detection, for example, a certainly occurring ADR could be wrongly interpreted as unlikely or not assessable due to lack of data. The signal detection process at Uppsala Monitoring Center collates the ADRs from all countries; while in fact there could be variation between the data received from different countries, at least one reason may be the variation in the ADR form itself. CONCLUSION The WHO receives information of the adverse events from all the countries that are members of the international drug monitoring program. These data are collated to generate potential signals; therefore, the data received by the WHO have to be uniform and complete to draw meaningful conclusions. Each country has its own spontaneous reporting form as per the individual countries requirements. However, our study reveals that the spontaneous reporting form from different countries is inadequate to capture detailed information. Therefore, there should be international guidelines and checklists for the inclusion of mandatory information needed for causality assessment for drafting and designing of spontaneous reporting form by countries. The Council for International Organization of Medical Sciences (CIOMS) (form which is the only international paper form used presently for spontaneous reporting of adverse drug reactions to collect data uniformly from all countries is incomplete with respect to the information asked for the outcome of the adverse drug reaction i.e., the form does not have an option for filling if the adverse reaction caused congenital anomaly and other medically important conditions. The most important thing missing is the reporter information which is one of the important criteria for accepting that the report as valid. Therefore, the introduction of guidelines for developing an effective spontaneous reporting form to capture complete adverse event-related information by WHO is the need of the hour. KEY POINTS Spontaneous ADR reporting form is a major tool of the pharmacovigilance system of any country. The ADR reporting forms is different for different countries thus leading to a lot of discrepancy in data captured by it. The WHO ADR monitoring centre collates information it receives from different counties. Non-uniformity of the form leads to WHO database itself being incomplete. Thus there is a need to harmonize the ADR reporting forms of all the countries to capture complete adverse event-related information.

5 QUALITY CHECK OF ADVERSE DRUG REACTIONs REFERENCES 1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a metaanalysis of prospective studies. JAMA 1998; 279: Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis and management. Lancet 2000; 356: World Health Organization. WHO Policy Perspectives on Medicines Pharmacovigilance: Ensuring the Safe Use of Medicines. Geneva Sten Olsson. The need for a generic form for spontaneous reporting of drug related problems Pharma Newsl 2007; 1: Central Drugs Standard Control Organization. Available from: Accessed on [20 March] Drug Control Organization Ministry of Health. Adverse Drug Reaction Reporting Form, Pakistan. Available: Accessed on [20 March] U.S. Food and Drug Administration. Adverse Drug Reaction Reporting Form, United States of America. Available: Accessed on [19 March] The Medicines & Healthcare Products Regulatory Agency (MHRA). Adverse Drug Reaction Reporting Form, United Kingdom. Available: Accessed on [22 March] Pharmacy and Poisons Board Kenya Adverse Drug Reaction Reporting Form, Kenya. Available: org Accessed on [20 March] National Pharmaceutical Control Bureau. Adverse Drug Reaction Reporting Form, Malaysia. Available: Accessed on [20 March] Health Canada. Adverse Drug Reaction Reporting Form, Canada. Available: Accessed on [25 March] Therapeutics Goods Administration, Adverse Drug Reaction Reporting Form, Australia. Available: Accessed on [22 March] Health Kwazulu-Natal. Adverse Drug Reaction Reporting Form, South Africa. Available: Accessed on [20 March] Tanzania Food and Drugs Authority Adverse Drug Reaction Reporting Form, United Republic of Tanzania. Available: adr/html Accessed on [25 March] 2009.