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Magistro baigiamajame darbe bus išanalizuoti Lietuvos farmakologinio budrumo reglamentavimo pasikeitimai, iškeltos nepageidaujamų reakcijų ar kitų su vaistiniu preparatu susijusių kėblumų nustatymo, vertinimo ir pranešimo problemos bei pateikti siūlymai, kaip šias problemas spręsti. Pirmoje darbo dalyje teoriniu požiūriu bus tiriamas farmakologinis budrumas lietuvoje. Antroje dalyje bus nagrinėjamas atliktas tyrimas, kuriuo norima išsiaiškinti dėl kokių dažniausių nepageidaujamų reakcijų pacientai kreipiasi. / Master's thesis will analyze changes of pharmacovigilance regulatory in Lithuania, brought adverse reactions or other drug-related embarrassment identification, assessment and reporting problems and give suggestions on how to address these issues. On first part will be studied theoretically pharmacovigilance in Lithuania. On second part will be examined the study, what are the adverese reactions in wich patients complain.

Le recours aux prescriptions sans ou hors AMM, dû principalement au manque d’essais cliniques, est très largement répandu en pédiatrie en particulier chez le nouveau-né. Les prescriptions hors AMM constituent un facteur de risque dans la survenue des effets indésirables médicamenteux (EIM). La pharmacovigilance est indispensable mais insuffisante afin d’évaluer le rapport bénéfice/risque des traitements en particulier lorsque les prescriptions hors AMM sont fréquentes. En combinant plusieurs approches pharmacoépidémiologiques, méta-analytiques et pharmacométriques, ce travail de thèse a pour objectifs de décrire les prescriptions hors AMM en néonatologie et explorer des approches qui permettront d’aboutir à mieux estimer le rapport bénéfice/risque des médicaments pour les enfants. Nous avons confirmé que le taux de prescription hors AMM en néonatologie est important (46%). Même en absence de soins de réanimation, plus de deux tiers des nouveaux-nés reçoivent au moins un médicament hors AMM pendant leur hospitalisation. En utilisant une approche méta-analytique explorant le rapport bénéfice risque du fluconazole en néonatologie en fonction du risque de base dans chaque étude (taux d’infection <10%), nous avons montré que la prophylaxie ciblée sur le risque de base serait plus bénéfique que la prophylaxie systématique des infections fongiques invasives. Nos travaux en pharmacovigilance pédiatrique, ont montré que les deux méthodes de détection actives (collaboration entre pharmaciens et cliniciens et le « trigger tool »), utilisant les dossiers patients informatisés, sont faisables et plus efficaces que la notification spontanée / Many drugs used to treat children in hospitals are either not licensed for use in children or are prescribed outside the terms of their product license (off-label prescribing) because of the lack of clinical trials in this population, and practical difficulties to involve children in clinical research. Drugs used within the specifications of the product license should therefore be less likely to cause ADRs compared to drugs that are either unlicensed or off-label for use in children. With different approaches such as pharmacoepidemiologic, meta-analytic and pharmacometrics, we sought to improve the estimate of the benefit risk ratio of medicines used for treating children. Our observational prospective study in a neonatal unit demonstrated that the prescriptions of unlicensed or off-label drugs in neonatal unit is common (46%). We also used meta-analytic approach in order to estimate the benefit risk ratio of the prophylactic use of fluconazole as a function of the baseline risk. Our results suggest that “systematic fluconazole prophylaxis for all VLBW in NICUs is not warranted by the available evidence and should be adapted to the baseline risk. We also showed that active drug monitoring by using electronic patient files by targeting review chart with a trigger tool in neonates and with close collaboration between the pharmacovigilance center, pharmacologists, and clinicians was necessary and feasible for improving the detection of ADRs in children

L'évaluation des données de sécurité du médicament reste encore limitée dans les pays en voie de développement. La création du Centre National de Pharmacovigilance du Vietnam en 2009 a permis l'enregistrement des notifications spontanées d'effets indésirables (EIs) permettant une analyse quantitative et qualitative et de générer des éventuels signaux de pharmacovigilance. Les objectifs principaux de la thèse étaient : (i) décrire le système de pharmacovigilance vietnamien, et comparer les données à travers quelques exemples, au système de pharmacovigilance français, (ii) appliquer un ensemble d'approches pharmaco-épidémiologiques pour identifier les risques médicamenteux au Vietnam et (iii) améliorer la sous-notification des EIs. Nous introduisons pour la première fois, un bilan complet du système de pharmacovigilance vietnamien avec une série de suggestions pour les pays partageant le même contexte de ressources limitées. Quelques résultats et défis pour le développement durable du système ont également été discutés. Secondairement, nous avons utilisé les bases de données de pharmacovigilance vietnamienne et française pour comparer le profil de notification pour 2 types d'EIs : anaphylaxie et syndrome de Steven-Johnson et nécrolyse épidermique toxique (SSJ/NET) d'origine médicamenteuse. Nous avons généré les premiers signaux de pharmacovigilance vietnamienne : l'allopurinol, la carbamazépine, les médicaments traditionnels, la colchicine, l'acide valproïque et le méloxicam ont généré des signaux pour le SSJ/NET - déjà connus dans littérature. Par ailleurs, nous avons retrouvé des signaux significatifs pour le cefixime et le paracétamol. Pour l'anaphylaxie, nous avons identifié 4873 (13.2%) cas dans la base vietnamienne pendant la période 2010-2016 avec une tendance à l'augmentation au cours du temps. Les antibiotiques (notamment céphalosporines de 3ème génération) sont les causes principales de l'anaphylaxie médicamenteuse au Vietnam. De plus, des signaux pour certains médicaments comme l'alpha-chymotrypsine, l'amoxicilline/sulbactame et les solutions de glucose ou électrolytes peuvent être typiques pour les pays en voie de développement. Enfin, l'identification des EIs à partir des données de laboratoire de biologie de l'hôpital pourrait améliorer le taux de notification d'EI au Vietnam. [...] / The understanding and quantitative analysis in drug safety domain among developing countries remain still limited. The creation of the National Drug Information and Adverse Drug Reaction Monitoring Centre (NDIADRMC) of Vietnam in 2009 was a landmark for the pharmacovigilance activities in this country and allowed the registration of spontaneous adverse drug reaction (ADR) reports. The accumulation of National Pharmacovigilance Database of Vietnam (NPDV) requires a quantitative and qualitative analysis and generation of pharmacovigilance signals to better protect Vietnamese people's health. The main objectives of the thesis are: (i) describe the Vietnamese pharmacovigilance system, with the comparison to another developed pharmacovigilance system as a reference (France), (ii) apply a set of pharmacoepidemiological approaches to identify the specific drug-related risks, and (iii) improve the under-reporting issue in Vietnam. Firstly, we introduce a full-detailed overview of Vietnamese pharmacovigilance system with a series of lessons learned for the other countries sharing the similar limited-resource context. Some achievements and challenges for the sustainable development of the system were also equitably discussed. Secondly, we used the Vietnamese and French pharmacovigilance databases to compare the differences in characteristics of two types of ADR: anaphylaxis and Steven-Johnson's syndrome and toxic epidermal necrolysis (SJS/TEN) induced by medications. Next, we generated the first Vietnamese pharmacovigilance signals. The signals of drug-induced SJS/TEN were generated with allopurinol, carbamazepine, traditional or herbal drugs, colchicine, valproic acid and meloxicam which were similar to the other previously studies in literature. Furthermore, we also found the significant signals of cefixime and paracetamol. For drug-induced anaphylaxis, we identified 4873 (13.2%) cases in the Vietnamese database during the period 2010-2016 with an increasing trend over time. The antibiotics (especially the third-generation cephalosporins) were the main causes of drug-induced anaphylaxis in Vietnam. In addition, the signals were generated with several drugs such as alpha-chymotrypsin, amoxicillin/sulbactam and glucose or electrolyte solutions which were typical for the resource-restricted countries. On the other hand, the identification of ADR through the screening the laboratory test results could help to increase the ADR reporting rate in Vietnam. [...]

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Introdução: A automedicação é uma prática frequente em diferentes culturas, que pode ser usada como estratégia para resolução de pequenos problemas de saúde, especialmente em populações cujo acesso a serviços de saúde é restrito. No entanto, essa prática pode, também, ocasionar reações adversas graves, resistência microbiana, interações medicamentosas e gastos desnecessários, especialmente em grupos economicamente desfavorecidos e socialmente excluídos como ocorre com os povos ribeirinhos. Objetivo: Analisar a prática de automedicação e fatores associados entre ribeirinhos da região do Médio Solimões - Amazonas. Método: Estudo transversal de base populacional realizado nas comunidades ribeirinhas do município de Coari - Amazonas. A amostra probabilística foi composta por 492 ribeirinhos adultos. A coleta de dados foi realizada nas comunidades por meio de um questionário composto por variáveis independentes: socioeconômicas, demográficas, de acesso aos serviços de saúde, consumo de drogas lícitas, enfermidades autorrelatadas e informações sobre o consumo de medicamentos. A variável dependente automedicação foi avaliada pelo uso de pelo menos um medicamento sem prescrição médica ou de dentista, nos últimos 30 dias. Na análise dos dados utilizou-se testes do Qui-quadrado ou exato de Fischer, teste t de Student ou de Wilcoxon-Mann-Whitney e regressão logística binária hierarquizada. Resultados: A prevalência da automedicação foi de 76,3%. Dor de diferentes origens (58,1%) foi o principal motivo que levou à automedicação. Analgésicos (57,5%) e antimicrobianos (13,0%) foram os medicamentos mais utilizados. Os fatores associados à automedicação foram sexo masculino (OR=2,20; IC=1,21-4,01), faixa etária entre 18 a 39 anos (OR=2,50; IC=1,06-5,91), não procura por serviços de saúde (OR=2,90; IC=1,66-5,09), tempo de deslocamento da comunidade à zona urbana entre 1 a 4 horas (OR=2,84; IC=1,26-6,41) e maior que 4 horas (OR=5,27; IC=2,18-12,74), ter o hábito de consumo de medicamentos alopáticos por conta própria (OR=3,14; IC=1,49-6,61). Conclusões: Na população ribeirinha, a prática elevada da automedicação reflete a necessidade de busca de autocuidado pelas pessoas, sobretudo decorrente do restrito acesso aos serviços de saúde. / Introduction: Self-medication is a frequent practice in different cultures, and it can be used as a strategy to solve minor health problems, especially among populations with restricted access to health care services. However, such a practice may cause serious adverse reactions, microbial resistance, drug interactions and unnecessary expenses, mainly for economically disadvantaged and socially excluded groups like the riverside communities. Objective: To analyze the self-medication practice and its related factors among riverside communities in the region of the Middle portion of the Solimões River Amazonas State, Brazil. Method: Cross-sectional, population-based study carried out among riverside communities in the municipality of Coari Amazonas State, Brazil. The probability sampling comprised 492 adult riverside dwellers. Data collection was held in the communities by means of a questionnaire including independent variables: socioeconomic, demographic ones, access to health care services, drug therapy, self-reported illnesses, and information on medication use. Medication dependent variable was assessed by the use of at least one drug without medical or dentists prescription in the past 30 days. For the data analysis, Chi-square test or Fischers exact test, Students t or Wilcoxon-Mann-Whitney tests, and hierarchical binary logistic regression were used. Results: Self-medication prevalence was 76.3%. Pain from different origins (58.1%) was the main reason for self-medication. Painkillers (57.5%) and antimicrobial medication (13.0%) were the most used drugs. Self-medication related factors were males (OR=2.20; CI=1.21-4.01), age range between 18 and 39 years (OR=2.50; CI=1.06-5.91), not search for health care services (OR=2.90; IC=1.66-5.09), travel time from the community to the urban center between 1 and 4 hours (OR=2.84; CI=1.26-6.41), and over 4 hours (OR=5.27; CI=2.18-12.74), habit of self-medication for allopathic drugs (OR=3.14; CI=1.49-6.61). Conclusions: High self-medication practice among the riverside population reflects the need for turning to self-medication, mainly due to the restricted access to health care services.

Problemas relacionados a medicamentos (PRMs) compreendem erros de medicação (EMs) e reações adversas a medicamentos (RAMs). Este estudo teve por objetivo analisar, classificar, quantificar e intervir nos PRMs ocorridos em pacientes idosos internados. Este estudo prospectivo descritivo de uma série de casos clínicos abrangeu 28 pacientes e 100 prescrições aleatórias a eles destinadas. A identificação dos PRMs se deu por métodos de farmacovigilância ativa e as intervenções farmacêuticas (IFs) foram realizadas diretamente junto à equipe médica. Medicamentos de uso potencialmente inapropriado para idosos foram utilizados por 21,4% dos pacientes; 19% das prescrições possuíam rasuras. Foram encontrados 924 PRMs, sendo 920 EMs e 4 possíveis RAMs, sendo uma delas confirmada. A maioria dos EMs foi classificada como sem prejuízo ao paciente. Foram realizadas 143 IFs em 73 prescrições de 92,9% dos pacientes, sendo a maioria (77,6%) acatada pela equipe médica. Apesar das limitações, demonstrou-se a importância do farmacêutico na investigação, prevenção e solução de PRMs. / Drug related problems (DRPs) include medication errors (MEs) and adverse drug reactions (ADRs). The objective of this study was to analyze, classify, quantify and intervene in DRPs occurred in hospitalized elderly patients. This prospective descriptive study of a case series included 28 patients and 100 random prescriptions to them addressed. The identification of DRPs was carry out by methods of active pharmacovigilance and the pharmaceutical interventions (PIs) were performed directly with the medical staff. Drugs potentially inappropriate for the elderly were used by 21.4% of the patients; 19% of the prescriptions had rasures. There were 924 DRPs, with 920 MEs and 4 possible ADRs 4, one of which confirmed. The majority of MEs was classified as \"without harm to the patient\". Were carried out 143 PIs on 73 prescriptions of 92.9% of the patients, being the majority (77.6%) fully embraced by the medical staff. Despite the limitations, it was possible to demonstrate the pharmacist importance in research, prevention and resolution of DRPs.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / AtravÃs de um acompanhamento contÃnuo de pacientes ambulatoriais em uma Unidade de SaÃde da FamÃlia (UBASF) em Fortaleza/Ce, o presente trabalho alÃm de descrever o perfil de utilizaÃÃo a medicamentos, relata provÃveis reaÃÃes adversas a fitoterÃpicos do programa FarmÃcia Viva, largamente utilizados como alternativa terapÃutica na rede pÃblica de saÃde, jà que aos mesmos normalmente nÃo sÃo atribuÃdos reaÃÃes adversas alÃm da existÃncia de poucos trabalhos cientÃficos publicados. Conhecer o perfil de utilizaÃÃo a medicamentos e de reaÃÃes adversas a fitoterÃpicos pertencente ao Programa FarmÃcias Vivas da Prefeitura de Fortaleza e assim contribuir para seu uso seguro e eficaz. Participaram do estudo pessoas que moravam em Fortaleza e foram atendidos na UBASF e que receberam prescriÃÃo mÃdica/enfermagem para a utilizaÃÃo de tais fitoterÃpicos no perÃodo de 01 de abril e 31 de julho de 2004, que concordaram em participar. O acompanhamento dos pacientes/usuÃrios foi realizado atravÃs de ligaÃÃes telefÃnicas e/ou retorno do responsÃvel/paciente à farmÃcia do posto de saÃde e/ou visitas domiciliares. Foram realizados 112 monitorizaÃÃes, 70,50% foram do sexo feminino e 29,50% do sexo masculino, com mÃdia de idade de 27,66 anos. Dos 299 medicamentos prescritos 58,53 % foram alopÃticos e 41,47 % fitoterÃpicos; a mÃdia de medicamentos por prescriÃÃo foi de 1,11 e a mÃdia de fitoterÃpicos foi de 1,56. Dos pacientes 89,30% utilizaram apenas 1 (um) medicamento do Programa FarmÃcia Viva e 25% utilizaram o fitoterÃpico como Ãnica opÃÃo de tratamento. Foram observados 11 notificaÃÃes de Suspeita de ReaÃÃo Adversa a Medicamentos, com o envolvimento de 7 medicamentos (3 fitoterÃpicos do Programa FarmÃcias Vivas e 4 alopÃticos). Dos 10 pacientes que apresentaram RAM, 2 eram masculino e 8 feminino, e 2 eram crianÃas. Sistema Digestivo (N=4) seguido do Sistema RespiratÃrio (N=3) e do Sistema Cardiovascular (N=2) foram os grupos terapÃuticos mais atingidos. Quanto à classificaÃÃo: 1 RAM foi definida, 4 provÃveis e 3 possÃveis; leve em 5 casos, moderada em 3 e nenhuma foi considerada Grave. Foram registrados 7 casos de queixa-tÃcnica. O nÃmero de reaÃÃes adversas notificadas foi significativo comparado com outros estudos. à necessÃrio a realizaÃÃo de estudos de eficÃcia e toxicidade dos fitoterÃpicos assim como a divulgaÃÃo do sistema de farmacovigilÃncia dos mesmos entre profissionais da saÃde a fim de que se tenha uma utilizaÃÃo mais segura e racional dos mesmos. / Through a continuous attendance of ambulatory patients in a Unit of Health of the Family in Fortaleza/Ce, the present work besides describing the use profile to medicines, tells to probable adverse reactions the phytotherapic of the program Alive Pharmacy, wide used as alternative therapeutic in the public net of health, since to the same ones adverse reactions are not usually attributed besides the existence of few published scientific works. To know the profile of use the medicines and adverse reactions the phytotherapic pertaining to the program alive pharmacies of the city hall of Fortaleza and thus to contribute for its safe and efficient use. They participated in the study people that lived in Fortaleza and they were assisted in the UBASF and that they received prescription for the use of such fitoterÃpicos in the period of April 01 and July 31, 2004, that they agreed in participating. The accompaniment was carried through telephonic linkings and/or responsible return of patient to the pharmacy of the domiciliary rank of health and/or the visits. 112 monitoring had been carried through, 70.50% had been of feminine sex and 29.50% of the masculine sex, with average of age of 27,66 years. Of 299 prescribed medicines 58.53% they had been allopathic and 41.47% phytotherapic; the medicine average for prescription was of 1,11 and the average of phytotherapic was of 1,56. Of patients 89.30% they had used only 1 (one) medicine of the Program Alive Pharmacy and 25% had used the phytotherapic as only option of treatment. The Medicines had been observed 11 notifications of Suspicion of Adverse Reaction, with the envolvement of 7 medicines (3 phytotherapic of the Program Alive Pharmacies and 4 allopathic). Of the 10 patients who had presented RAM, 2 were masculine and 8 feminine, and 2 were children. Digestive system (N=4) followed of the Respiratory System (N=3) and of the Cardiovascular System (N=2) had been the reached therapeutical groups more. How much to the classification: 1 RAM was defined, 4 probable and 3 possible ones; it has led in 5 cases, moderate in 3 and none was considered severe. They had been registered 7 cases of complaint-technique. The number of notified adverse reactions significant was compared with other studies. It is necessary the accomplishment of studies of effectiveness and toxicity of the phytotherapic as well as the popularization of the system of pharmacovigilance of the same ones among professionals of the health so that a safer and rational use.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-06-12T17:50:33Z No. of bitstreams: 1 MarceloGoncalves.pdf: 4815903 bytes, checksum: 2cb4067cbb604079481da44e19c54d1f (MD5) / Made available in DSpace on 2017-06-12T17:50:33Z (GMT). No. of bitstreams: 1 MarceloGoncalves.pdf: 4815903 bytes, checksum: 2cb4067cbb604079481da44e19c54d1f (MD5) Previous issue date: 2016-07-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / For most of the population, the difficult access to health services and the trend to use natural products in recovery and preservation of well-being have led to a rise in plants consumption as well as their derivatives as a therapeutic resource, which is very dangerous, considering the risks associated with inadequate conditions of trade and the quality of these products. For this, the present study has evaluated marketing conditions and the quality of some natural products found in private pharmacies and drugstores in São Luís, Maranhão; aiming to contribute to the actions of Pharmacovigilance in Phytotherapy. Based on data available by the Regional Pharmacy Council of the State of Maranhão, through random stratified samples, 15 drug stores and 17 pharmacies were selected to have market conditions investigated by having semi-structured interviews applied to pharmacists, pharmacy owners or assistants pharmacies or drugstores. Camellia sinensis (L.) Kuntze (green tea), Maytenus ilicifolia Mart. ex Reissek (espinheira-santa), Rhamnus purshiana DC. (sacred bark), Cynara scolymus L. (artichoke) and Matricaria recutita L. (chamomile) were identified as the most traded species so samples were acquired for integrity and purity analysis. As a result, it has been possible to observe inadequate marketing conditions, mainly serious health violations, in every selected pharmaceutical establishment. The purity and integrity analysis of commercial samples of green tea and chamomile have identified poor quality, confirming the presence of improper material. Moreover, no evidence of analytical markers or assets defined in specific literature were found. Thus, the results allow evidencing the need for increased surveillance, monitoring and quality control of plant material for medicinal purposes available for sale. / O difícil acesso de grande parte da população aos serviços de saúde e a tendência da sociedade em utilizar preferencialmente produtos naturais de origem vegetal na recuperação e/ou preservação da saúde têm ocasionado a crescente ascensão no consumo de plantas e/ou seus produtos derivados como recurso terapêutico; situação reocupante, considerando os riscos associados às condições inadequadas de comércio e qualidade desses produtos. Nesse sentido, o presente estudo avaliou as condições de comercialização e qualidade de produtos naturais disponibilizados em farmácias e drogarias privadas de São Luís, Maranhão; visando contribuir para as ações de Farmacovigilância em Fitoterapia. A partir de dados do Conselho Regional de Farmácia do Estado do Maranhão, por amostragem aleatória estratificada, foram selecionadas 15 drogarias e 17 farmácias para investigar as condições de comercialização, com emprego de entrevistas semiestruturadas aos farmacêuticos, proprietários ou auxiliares de farmácias ou drogarias. Camellia sinensis (L.) Kuntze (chá verde), Maytenus ilicifolia Mart. ex ReisseK (espinheira-santa), Rhamnus purshiana DC. (cáscara-sagrada), Cynara scolymus L. (alcachofra) e Matricaria recutita L. (camomila) foram identificadas como as espécies vegetais mais comercializadas, sendo adquiridas amostras para análise da integridade e pureza. Os resultados permitiram evidenciarmos condições inadequadas de comercialização nos estabelecimentos farmacêuticos selecionados com destaque a graves infrações sanitárias. As análises de pureza e integridade das amostras comerciais de chá verde e camomila comprovaram má qualidade, com a constatação da presença de materiais estranhos; como a não comprovação de marcadores analíticos e/ou ativos definidos na literatura especializada. Assim, os resultados permitem evidenciar a necessidade de maior fiscalização, vigilância e controle de qualidade do material vegetal para fins medicinais disponibilizados para comercialização.

<p>The WHO database contains more than 2.8 million case reports of suspected adverse drug reactions reported from 70 countries worldwide since 1968. The Uppsala Monitoring Centre maintains and analyses this database for new signals on behalf of the WHO Programme for International Drug Monitoring. A goal of the Programme is to detect signals, where a signal is defined as "Reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously."</p><p>The analysis of such a large amount of data on a case by case basis is impossible with the resources available. Therefore a quantitative, data mining procedure has been developed to improve the focus of the clinical signal detection process. The method used, is referred to as the BCPNN (Bayesian Confidence Propagation Neural Network). This not only assists in the early detection of adverse drug reactions (ADRs) but also further analysis of such signals. The method uses Bayesian statistical principles to quantify apparent dependencies in the data set. This quantifies the degree to which a specific drug- ADR combination is different from a background (in this case the WHO database). The measure of disproportionality used, is referred to as the Information Component (IC) because of its' origins in Information Theory. A confidence interval is calculated for the IC of each combination. A neural network approach allows all drug-ADR combinations in the database to be analysed in an automated manner. Evaluations of the effectiveness of the BCPNN in signal detection are described.</p><p>To compare how a drug association compares in unexpectedness to related drugs, which might be used for the same clinical indication, the method is extended to consideration of groups of drugs. The benefits and limitations of this approach are discussed with examples of known group effects (ACE inhibitors - coughing and antihistamines - heart rate and rhythm disorders.) An example of a clinically important, novel signal found using the BCPNN approach is also presented. The signal of antipsychotics linked with heart muscle disorder was detected using the BCPNN and reported.</p><p>The BCPNN is now routinely used in signal detection to search single drug - single ADR combinations. The extension of the BCPNN to discover 'unexpected' complex dependencies between groups of drugs and adverse reactions is described. A recurrent neural network method has been developed for finding complex patterns in incomplete and noisy data sets. The method is demonstrated on an artificial test set. Implementation on real data is demonstrated by examining the pattern of adverse reactions highlighted for the drug haloperidol. Clinically important, complex relationships in this kind of data are previously unexplored.</p><p>The BCPNN method has been shown and tested for use in routine signal detection, refining signals and in finding complex patterns. The usefulness of the output is influenced by the quality of the data in the database. Therefore, this method should be used to detect, rather than evaluate signals. The need for clinical analyses of case series remains crucial.</p>