Value and Implementation of the Aggregate Safety Assessment Plan.

Aggregate safety assessment involves evaluation of the totality of safety data to characterize the emerging safety profile of a product. The Drug Information Association-American Statistical Association Interdisciplinary Safety Evaluation scientific working group recently published an approach to developing an Aggregate Safety Assessment Plan (ASAP). Creation of an ASAP facilitates a consistent approach to safety data collection and analysis across studies and minimizes important missing data at the time of regulatory submission. A critical aspect of the ASAP is identification of the Safety Topics of Interest (STOI). The STOI, as defined in the ASAP, comprises adverse events (AEs), which have the potential to impact the benefit: risk profile of a product and typically require specialized data collection or analyses. While there are clear benefits to developing an ASAP for a drug development program, multiple concerns may be encountered with implementation. This article uses the examples of two STOIs to demonstrate the benefits and efficiencies gained with implementation of the ASAP in safety planning as well as in optimally characterizing the emerging safety profile of a product.

The role of pharmacies in haematopoietic stem cell transplantation process: A nationwide survey by Gruppo Italiano Trapianto di Midollo Osseo.

WHAT IS KNOWN AND OBJECTIVE: The aim of this survey, conducted by the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), was to evaluate the involvement of pharmacists in the haematopoietic stem cell transplant (HSCT) program in Italian adult and paediatric centres. METHODS: A 63-item online questionnaire was developed and sent to the Italian Transplant Programs on behalf of GITMO. RESULTS AND DISCUSSION: Overall, 54.7% of the Italian HSCT centres participated in the survey (88.5% adult, 7.7% paediatric, 3.8% mixed), of which 50% were in public hospitals and 50% affiliated with public universities. Just over 80% declared that a pharmacist is involved in the HSCT centre, and 86.5% reported the presence of a documentation system to signal of adverse events, accessible by physicians, nurses and pharmacists in 57.7%. Chemotherapy drugs were centralized in the pharmacy in 98.1% of HSCT centres, while parenteral nutrition was centralized in 55.8%. The use of off-label drugs was authorized by an internal committee and by the regional health authorities in 88.5% of the centres. On univariate analysis, few statistically significant differences were found on response frequencies between public hospitals and university centres or between HSCT centres performing only autologous stem cell transplantation versus other centres performing autologous and allogeneic stem cell transplantation. WHAT IS NEW AND CONCLUSION: This survey suggests that there is good collaboration between pharmacists and physicians and nurses in Italian HSCT transplantation centres. The enhancement of pharmacists dedicated to HSCT programs could improve some problems, for example, the centralization of parenteral nutrition.

National pharmacovigilance programs in Arab countries: A quantitative assessment study.

PURPOSES: The aim of the pharmacovigilance (PV) process is to bring together all the much-needed information about various aspects of product safety or, in particular, the safety and vigilance of drugs as pharmaceutical products. This study aimed to investigate and provide an overview on the current situation and activities of the national PV centers in Arab countries. METHODS: A cross sectional study was conducted between March and May in 2018. The current survey was adopted and modified from a study that used the questionnaire designed by the World Health Organization Collaborating Centre for International Drug Monitoring. The national PV centers of 22 Arab countries were invited to participate in this study. Descriptive analyses were conducted utilizing the analysis services provided by SurveyMonkey. RESULTS: In total of, 15 countries responded to our invitation (response rate: 68%). Most Arab countries started their PV program in the last decade, with Palestine implementing its program in 2017. Among the respondents, nine (60%) were members of the WHO International Drug Monitoring Program and were all users of the software provided by the WHO Uppsala Monitoring Center (VigiFlow or VigiBase), except Sudan. In 2017, a total of 27 502 reports were received by the centers in the studied countries, ranging from three reports received in Lebanon to a total of 7362 reports received by the national program of Algeria. CONCLUSIONS: An improvement was noticed among the national PV programs in the Arab countries. However, a considerable difference still exists among the countries in terms of the implementation and practice of PV.

Empirical assessment of case-based methods for drug safety alert identification in the French National Healthcare System database (SNDS): Methodology of the ALCAPONE project.

OBJECTIVES: To introduce the methodology of the ALCAPONE project. BACKGROUND: The French National Healthcare System Database (SNDS), covering 99% of the French population, provides a potentially valuable opportunity for drug safety alert generation. ALCAPONE aimed to assess empirically in the SNDS case-based designs for alert generation related to four health outcomes of interest. METHODS: ALCAPONE used a reference set adapted from observational medical outcomes partnership (OMOP) and Exploring and Understanding Adverse Drug Reactions (EU-ADR) project, with four outcomes-acute liver injury (ALI), myocardial infarction (MI), acute kidney injury (AKI), and upper gastrointestinal bleeding (UGIB)-and positive and negative drug controls. ALCAPONE consisted of four main phases: (1) data preparation to fit the OMOP Common Data Model and select the drug controls; (2) detection of the selected controls via three case-based designs: case-population, case-control, and self-controlled case series, including design variants (varying risk window, adjustment strategy, etc.); (3) comparison of design variant performance (area under the ROC curve, mean square error, etc.); and (4) selection of the optimal design variants and their calibration for each outcome. RESULTS: Over 2009-2014, 5225 cases of ALI, 354 109 MI, 12 633 AKI, and 156 057 UGIB were identified using specific definitions. The number of detectable drugs ranged from 61 for MI to 25 for ALI. Design variants generated more than 50 000 points estimates. Results by outcome will be published in forthcoming papers. CONCLUSIONS: ALCAPONE has shown the interest of the empirical assessment of pharmacoepidemiological approaches for drug safety alert generation and may encourage other researchers to do the same in other databases.

Automation Opportunities in Pharmacovigilance: An Industry Survey.

BACKGROUND: TransCelerate's Intelligent Automation Opportunities (IAO) in Pharmacovigilance initiative has been working to evaluate various pharmacovigilance processes to facilitate systematic innovation with intelligent automation across the entire area. The individual case safety report (ICSR) process was the first process selected for evaluation because of its resource-intensive nature, risk of errors, and operational inefficiencies. OBJECTIVES: TransCelerate's IAO in Pharmacovigilance initiative initially worked to articulate an end-to-end ICSR process that would generically apply to various pharmacovigilance organizations, despite organizational variations in specific ICSR process steps. This paper aims to address the need for a systematic review framework for automation of the ICSR process from the value, impact, perceived risk, and opportunity point of view. METHODS: The generic ICSR process, which starts with receipt of an adverse event report, was grouped into three process blocks: case intake, case processing, and case reporting. Each of these was then further detailed in individual process steps. A total of 19 TransCelerate member companies were invited to complete a survey designed to facilitate understanding of automation opportunities across the ICSR process. Heat maps of the current level of effort, expected benefit of automation, and perceived risk of automation were compiled from responses to identify intelligent automation opportunities for specific ICSR process steps. Relevant experts on the TransCelerate evaluation team analyzed and interpreted the anonymized and aggregated results. RESULTS: In total, 15 TransCelerate member companies responded to the survey and indicated that ICSR process steps with current high effort, expected high automation benefit, low or manageable automation risk, and low levels of current automation present the best opportunities for future automation. Such steps include language translations, case verification, in-line quality control, prioritization/triage, data entry, alerts for cases of interest, workflow management, and monitoring. Some steps (e.g., submission) have been automated for a number of years and appear on the heat map as having low potential for further automation. The survey responses implied that, despite successful use of intelligent automation technologies in other areas, adoption within pharmacovigilance and the ICSR process in particular remains limited. The perceived high risk to patient safety is expected to decrease with additional successful applications in pharmacovigilance. CONCLUSIONS: Our results highlight the areas of greatest opportunity for intelligent automation based on the potential benefits of applying intelligent automation and the perceived risks associated with each ICSR process step. Responding TransCelerate member companies already automate many steps to varying degrees. However, a significant opportunity remains for automation to penetrate further. Additionally, the pharmacovigilance industry culture needs to change in order to reduce the perceived risk of automation and to encourage a more progressive approach to intelligent automation. Increased automation is crucial to empower agile and efficient pharmacovigilance.

Comparative Assessment of the National Pharmacovigilance Systems in East Africa: Ethiopia, Kenya, Rwanda and Tanzania.

INTRODUCTION: The increased access to medicinal products in Africa is not well-matched with the pharmacovigilance capacity to monitor drug safety. The objective of this study was to assess the functionality and identify the strengths and limitations of the national pharmacovigilance systems in Ethiopia, Kenya, Rwanda, and Tanzania, and compare these systems. METHODS: Legal and statutory documents governing the pharmacovigilance systems of each participating country were examined by assessors prior to on-site review. The staff of the pharmacovigilance unit of the National Medicines Regulatory Authorities (NMRAs) were interviewed using the East African Community Harmonized Pharmacovigilance Indicators tool, supplemented with indicators from the World Health Organization (WHO) Global Benchmarking Tool. Responses were recorded, and data were analyzed. RESULTS: The pharmacovigilance systems were supported by law and regulations in line with international standards. Standard operating procedures for receiving, processing, and communicating suspected adverse event reports were in place, but reporting of suspected medicine-related harm from stakeholders was inadequate in all countries. The number of Individual Case Safety Reports (ICSRs) received by NMRAs in Kenya, Ethiopia, and Tanzania (mainland) were 35.0, 6.7, and 4.1 per million inhabitants, respectively, in the last calendar year. At the time of assessment, Rwanda did not have an operational system. Overall, ≤ 1% of the total number of health facilities per country submitted ICSRs. Only Kenya and Tanzania had a designated budget for pharmacovigilance activities and an electronic ICSR reporting system. The national pharmacovigilance systems in all four countries did not have access to data on drug utilization. CONCLUSIONS: The national pharmacovigilance systems in the four East African countries have policy and legal frameworks defined by law and regulation to conduct pharmacovigilance activities. However, the four national pharmacovigilance systems are at different levels of capacity and performance with respect to conducting pharmacovigilance activities. Targeted interventions are needed to strengthen the pharmacovigilance systems to enable evidence-based decision making for patient safety.

[Safety signal detection by the French Addictovigilance Network: Innovative methods of investigation, examples and usefulness for public health]. / Détection des signaux du réseau français d'addictovigilance : méthodes innovantes d'investigation, illustrations et utilité pour la santé publique.

The French Addictovigilance Network aims to monitor all psychoactive substances with abuse potential including prescription drugs and other legal and illegal substances such as new psychoactive substances (NPS) and its consequences in humans. Created in 1990 through a network of regional addictovigilance centres covering the entire country, these pharmacologists with expertise in addictovigilance have developed interface with different partners (physicians, toxicologists, network of community pharmacies, addictology care centers…) and implemented several original tools of pharmacosurveillance (such as DRAMES [death related to the abuse of medicines] in strong collaboration with toxicologists or such OPPIDUM [observation of illegal products and misuse of psychotropic medications]), complementary to the spontaneous reporting. A such multidimensional approach including proactive surveillance by these tools and also among several heterogenous data sources (such as data from hospitals or claims database) is able to detect early addictovigilance signals and warnings as illustrated with three following examples: cannabis use and acute serious cardiovascular disorders, new synthetic opioids (ocfentanil, carfentanil) and severe opiate overdose or deaths, the diverted use of psychoactive drugs (codeine analgesics or sedative H1 antihistamines called purple drank) by adolescents and young adults. The choice of a broad strategy and the multifaceted system implemented by the French Addictovigilance Network using elements of pharmacology (fundamental, clinical, pharmacoepidemiology) expertise is an innovative method to detect early addictovigilance signals, and to describe its characteristics in order to increase awareness of psychoactive substances by patients, users and health professionals.

Development and validation of a questionnaire for the assessment of the knowledge, management and reporting ADR in paediatrics by healthcare teams (QUESA-P).

OBJECTIVE: We aimed to develop and validate a new instrument called Questionnaire for the assessment of the knowledge, management and reporting ADR in Paediatrics by Healthcare teams (QUESA-P). DESIGN: This is a cross-sectional study. SETTINGS AND PARTICIPANTS: Teams of healthcare professionals (HCP) that lead with pharmacological therapy in Paediatrician's sector (Paediatric-HCP) in seven public hospitals in Brazil. OUTCOME: An assessment of the knowledge and current management of ADR in Paediatric-HCP. METHODS: We developed and validated QUESA-P, using a standardised procedure which included item development and psychometric prevalidation using Cronbach's Alpha, item-total correlation and test-retest validity for internal consistency and reliability. External criterion was used as criterion validation (the instrument was applied to the focus group expert vs focus group team of Paediatric-HCP in hospitals). The focus group of experts who participated in psychometrics was asked to respond to the QUESA-P twice in order to assess test-retest reliability. The content validity of the initial questionnaire was assessed by the Delphi method and pilot test. Subsequently, we made minor revisions and finalized the QUESA-P RESULTS: Selection of domains and facets were based on literature review made in duplicate by authors. Content validity was done by trial of different examiners (panellists, n=16), conducting analysis through Delphi method (three rounds). The QUESA-P was constructed with three domains. The intraclass correlations (0.80) and the Cronbach's alpha coefficient (0.82), indicated adequate test-retest reliability and internal consistency for each domain. The application of the QUESA to 61 Paediatric-HCP in hospital resulted in lower mean score of 42.1 ± 3.4 in all domains when compared with expert teams (n= 46) 48.2 ± 3.7 (p <0.001) indicating that the instrument is valid to discriminate QUESA experts and Paediatric-HCP. CONCLUSION: The selected domains can be used to check weaknesses in the identification, management and reporting of suspected ADR by Paediatric-HCP in Brazil.

Anatomy of Risk Evaluation and Mitigation Strategies (REMS).

This Chapter provides an introduction and overview of the U.S. FDA REMS program and applicable regulatory aspects. Topics covered include the 2015 Draft Guidance, organization structure and functions, a discussion on pharmacovigilance and adverse event reports, and a discussion of the applicability of REMS in oncology.

Causality assessment of adverse drug reaction reports using an expert-defined Bayesian network.

In pharmacovigilance, reported cases are considered suspected adverse drug reactions (ADR). Health authorities have thus adopted structured causality assessment methods, allowing the evaluation of the likelihood that a drug was the causal agent of an adverse reaction. The aim of this work was to develop and validate a new causality assessment support system used in a regional pharmacovigilance centre. A Bayesian network was developed, for which the structure was defined by experts while the parameters were learnt from 593 completely filled ADR reports evaluated by the Portuguese Northern Pharmacovigilance Centre medical expert between 2000 and 2012. Precision, recall and time to causality assessment (TTA) was evaluated, according to the WHO causality assessment guidelines, in a retrospective cohort of 466 reports (April-September 2014) and a prospective cohort of 1041 reports (January-December 2015). Additionally, a simplified assessment matrix was derived from the model, enabling its preliminary direct use by notifiers. Results show that the network was able to easily identify the higher levels of causality (recall above 80%), although struggling to assess reports with a lower level of causality. Nonetheless, the median (Q1:Q3) TTA was 4 (2:8) days using the network and 8 (5:14) days using global introspection, meaning the network allowed a faster time to assessment, which has a procedural deadline of 30 days, improving daily activities in the centre. The matrix expressed similar validity, allowing an immediate feedback to the notifiers, which may result in better future engagement of patients and health professionals in the pharmacovigilance system.

Pharmacovigilance in China: development and challenges.

Background Rational drug use and drug safety are becoming increasingly important concerns in China with the increasing public access to drugs and the health-care system, and this has led to the development of pharmacovigilance in China. Aim of the review To provide a brief introduction about pharmacovigilance in China in terms of system development, utilization and challenges. Method Relevant studies on pharmacovigilance related to the study aim was undertaken through literature search to synthesize the extracted data. Results The creation and evolvement of China's pharmacovigilance system spans across 30 years since 1989. The system consists of four progressing administrative layers: county, municipal, provincial and national levels. China has passed over 20 laws and regulations related to pharmacovigilance covering the processes of drug development, manufacture, distribution and use with the aim to guard drug safety. An online spontaneous self-reporting Adverse Drug Reaction (ADR) Monitoring System was established in 2003. ADRs are mainly reported by medical institutions, pharmaceutical manufacturers, and drug distributors. Currently there is no mandatory ADR reporting requirement for pharmaceutical manufacturers, and a proposed regulation under public comment will likely change this. China has started to build active pharmacovigilance surveillance programs in addition to the passive ADR reporting system. The China Food and Drug Administration has established the intensive Safety Monitoring Program and the National Adverse Drug Reaction Monitoring Sentinel Alliance Program based on electronic health records to further the efforts of ADR reporting, monitoring and analysis. Conclusion The practice of ADR monitoring and pharmacovigilance in China have made great progress. More efforts are needed both in system building, and creation of laws and regulations to strengthen the safe use of medicines.

Application and optimisation of the Comparison on Extreme Laboratory Tests (CERT) algorithm for detection of adverse drug reactions: Transferability across national boundaries.

PURPOSE: The Singapore regulatory agency for health products (Health Sciences Authority), in performing active surveillance of medicines and their potential harms, is open to new methods to achieve this goal. Laboratory tests are a potential source of data for this purpose. We have examined the performance of the Comparison on Extreme Laboratory Tests (CERT) algorithm, developed by Ajou University, Korea, as a potential tool for adverse drug reaction detection based on the electronic medical records of the Singapore health care system. METHODS: We implemented the original CERT algorithm, comparing extreme laboratory results pre- and post-drug exposure, and 5 variations thereof using 4.5 years of National University Hospital (NUH) electronic medical record data (31 869 588 laboratory tests, 6 699 591 drug dispensings from 272 328 hospitalizations). We investigated 6 drugs from the original CERT paper and an additional 47 drugs. We benchmarked results against a reference standard that we created from UpToDate 2015. RESULTS: The original CERT algorithm applied to all 53 drugs and 44 laboratory abnormalities yielded a positive predictive value (PPV) and sensitivity of 50.3% and 54.1%, respectively. By raising the minimum number of cases for each drug-laboratory abnormality pair from 2 to 400, the PPV and sensitivity increased to 53.9% and 67.2%, respectively. This post hoc variation, named CERT400, performed particularly well for drug-induced hepatic and renal toxicities. DISCUSSION: We have demonstrated that the CERT algorithm can be applied across national boundaries. One modification (CERT400) was able to identify adverse drug reaction signals from laboratory data with reasonable PPV and sensitivity, which indicates potential utility as a supplementary pharmacovigilance tool.

A time series analysis of the effects of financial incentives and mandatory clinical applications as interventions to improve spontaneous adverse drug reaction reporting by hospital medical staff in China.

RATIONALE, AIMS, AND OBJECTIVES: Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is often under-reported, which may lead to problems in patient management. This study was aimed to assess the effectiveness of a financial intervention based on a fine and a bonus for improving spontaneous reporting of ADRs by physicians in a hospital setting. METHODS: This study was conducted at the First Affiliated Hospital of Zhengzhou University (China). Starting in 2009, a bonus of 20 RMB (Chinese currency) was given for each spontaneous ADR report, and a fine of 50 RMB was given for any withheld ADR report. A time series analysis using autoregressive integrated moving average models was performed to assess the changes in the total number of spontaneous ADR reports between the preintervention period (2006-2008) and during the first (2009-2011) and second (2012-2014) intervention periods. RESULTS: The median number of reported ADRs per year increased from 29 (range 27-72) in the preintervention period to 277 (range 199-284) in the first intervention period and to 666 in the second (range 644-691). The monthly number of reported ADRs was stable during the 3 periods: 3.56 ± 3.60/month (95% confidence interval (CI), 2.42-4.75) during the preintervention period, 21 ± 13/month (95% CI, 16.97-25.80) in the first intervention period, and 56 ± 20/month (95% CI, 48.81-62.17) in the second intervention period. CONCLUSION: A financial incentive and ADR management regulations had a significant effect on the increase of reported ADRs.

Promoting and Protecting Public Health: How the European Union Pharmacovigilance System Works.

This article provides an overview of the European Union pharmacovigilance system resulting from the rationalisation and strengthening delivered through the implementation of the revised pharmacovigilance legislation. It outlines the system aims, underlying principles, components and drivers for future change. At its core, the Pharmacovigilance Risk Assessment Committee is responsible for assessing all aspects of the risk management of medicinal products, thus ensuring that medicines approved for the European Union market are optimally used by maximising their benefits and minimising risks. The main objectives of the system are to promote and protect public health by supporting the availability of medicines including those that fulfil previously unmet medical needs, and reducing the burden of adverse drug reactions. These are achieved through a proactive, risk proportionate and patient-centred approach, with high levels of transparency and engagement of civil society. In the European Union, pharmacovigilance is now fully integrated into the life cycle of medicinal products, with the planning of pharmacovigilance activities commencing before a medicine is placed on the market, and companies encouraged to start planning very early in development for high-innovation products. After authorisation, information on the safety of medicines continues to be obtained through a variety of sources, including spontaneous reports of adverse drug reactions or monitoring real-world data. Finally, the measurement of the impact of pharmacovigilance activities, auditing and inspections, as well as capacity building ensure that the system undergoes continuous improvement and can always rely on the best methodologies to safeguard public health.

A review of the National pharmacovigilance system in Malta - implementing and operating a pharmacovigilance management system.

INTRODUCTION: Regulatory authorities have a legal mandate to implement and maintain a Pharmacovigilance System designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance. Areas covered: This review maps the implementation of pharmacovigilance activities in Malta since accession in the EU in mid 2004 and discusses the challenges the Maltese Regulator encountered while setting up adequate and effective systems to fulfil its legal mandate. Areas reviewed are those around ADR reporting, promotion and safety communications including rapid alerts and recalls, direct healthcare professional communications, risk minimisation measures and safety circulars and quality systems. Expert opinion: Within a ten year period, 3 EU directives on pharmacovigilance were implemented by our agency. Despite limitations to resources, based on a prioritised implementation, the legislation provisions are now fully operational with a good level of sustainability. Lessons learnt from this process are discussed in this review. The coming years will involve strengthening and consolidation of existing processes.

Pharmacovigilance in Europe: Place of the Pharmacovigilance Risk Assessment Committee (PRAC) in organisation and decisional processes.

The new European legislation that came into force in July 2012 reinforced the organisation of pharmacovigilance by setting up a committee in charge of risk assessment for medicines, the Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC has a remit covering the assessment of all aspects of the safety and the risk management of medicinal products for human use in the European Union. It deals with issues regarding pharmacovigilance signals, the periodic evaluation of benefit/risk reports from marketing authorization holders (MAH), risk management plans, post-marketing studies, variations or renewals of marketing authorisations, management of under surveillance drugs lists, inspections for pharmacovigilance reasons and audits of pharmacovigilance systems. The PRAC works with the pharmacovigilance systems of the European Member States, which draw up evaluation reports. These evaluations are circulated and discussed by Member States so as to issue recommendations, which serve as a basis for other European medicines committees, the Committee for Medicinal Products for Human Use (CHMP) or the Coordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh) which then give their opinion. The final decision, which applies to all Member States and to the concerned MAH, lies with the European Commission (EC). This decisional procedure thus rests on coordination involving the PRAC, the CHMP, the CMDh, the EC, the Member States and the pharmaceutical companies. In the 3 years from July 2012, the PRAC has processed nearly 4500 procedures and is still facing an increasing workload.

Traceability of Biologics in The Netherlands: An Analysis of Information-Recording Systems in Clinical Practice and Spontaneous ADR Reports.

INTRODUCTION AND OBJECTIVE: Pharmacovigilance requirements for biologics mandate that EU Member States shall ensure that any biologic that is the subject of a suspected adverse drug reaction (ADR) is identifiable by brand name and batch number. Recent studies showed that brand name identification is well established, whereas batch numbers are (still) poorly reported. We evaluated information-recording systems and practices in the Dutch hospital setting to identify determinants for brand name and batch number recording as well as success factors and bottlenecks for traceability. METHODS: We surveyed Dutch hospital pharmacists with an online questionnaire on systems and practices in hospitals for recording brand names and batch numbers. Additionally, we performed an analysis of the traceability of recombinant biologics in spontaneous ADR reports (received between 2009 and 2014) from the Netherlands Pharmacovigilance Centre Lareb. RESULTS: The survey showed that brand names are not routinely recorded in the clinical practice of Dutch hospitals, whereas batch numbers are poorly recorded. Seventy-six percent of the 1523 ADR reports for recombinant biologics had a traceable brand name whereas 5% of these reports contained a batch number. The results suggest a possible relationship between the availability of brand and batch number information in clinical practice and the inclusion of this information in ADR reports for biologics. CONCLUSION: The limited traceability of brand names and batch numbers in ADR reports may be primarily caused by the shortcomings in the recording of information in clinical practice. We recommend efforts to improve information-recording systems as a first step to improve the traceability of biologics in ADR reporting.

Initial development and testing of an instrument for patient self-assessment of adverse drug reactions.

PURPOSE: To develop and conduct preliminary testing of a causality assessment tool for patients, for potential use in encouraging both discussions with clinicians about suspected adverse drug reactions (ADRs) and reporting to authorities. METHODS: Ten causality statements, developed from qualitative studies involving patients, with a scoring system allowing categorization, were embedded in a questionnaire which also included a symptom checklist and additional details about one suspected ADR and medicine, selected for causality assessment. Patients with experiences of suspected ADRs were involved in cognitive interviews (15), piloting (20) and psychometric testing (120). Test-retest reliability, construct validity and criterion-related validity were evaluated, through repeated causality assessment, comparison with a visual analogue scale assessing certainty of causality and comparison with causality assessment using World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria, respectively. The study involved outpatients at a university hospital in northeast Thailand. RESULTS: Ninety-eight patients completed causality assessment twice: both causality scores (Spearman rs = 0.715; p < 0.001) and causality classification [percentage of positive agreement (PPA) = 68.4; κ = 0.419; p < 0.001] showed satisfactory reliability. Causality scores were positively correlated with certainty of causality (Spearman rs = 0.556; p < 0.01). There was moderate agreement against WHO-UMC criteria [PPA = 70.4; κ = 0.440; p < 0.001]. Of the 91 completing an evaluation, 88% agreed that the tool should be used routinely, 78% agreed that it gave them useful results and 80% agreed that it was easy to use. CONCLUSIONS: This novel instrument has satisfactory psychometric properties and was acceptable to Thai patients, but it requires further testing. It has potential for use in supporting patients with suspected ADRs to discuss these with health professionals, and perhaps to report directly.