A checklist for critical appraisal of indirect comparisons.

The aim of this study was to develop a user-friendly checklist for critical appraisal of indirect comparisons of drugs, considering clinical, methodological/statistical and quality aspects, mainly to be applied in drug evaluation in the decision-making context. After conducting a review of the literature, we used group consensus to establish the key points of the checklist, focusing mainly on indirect comparisons, but including topics related to network meta-analysis or multiple treatment comparisons. The coordinating group elaborated the first draft, which was reviewed by external experts, re-evaluated by the coordinating group and finally assessed by 23 drug evaluation experts trained in indirect comparisons, who applied the checklist to one study. The Kappa index of agreement was calculated and the final checklist was developed by group consensus including the external experts. The checklist has two parts. The first consists of three eliminatory key questions while the second includes 17 items: 5 regarding quality, 5 regarding clinical issues and 7 dealing with methodology/statistics. The median kappa values of the 23 evaluations were 0.83 (range 0.67-0.93), 0.61 (0.54-0.91) and 0.36 (0.22-1) with regard to quality, clinical aspects and methodology/statistics, respectively. A structured checklist was developed to facilitate critical appraisal of key issues in indirect comparisons, including comments for assessing the consequences of its application to drug evaluation in the decision-making context. Agreement between reviewers in clinical and quality items was good, but weaker in methodology/statistics ones.

Direct and indirect comparison of the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in psoriatic arthritis.

WHAT IS KNOWN AND OBJECTIVE: Psoriatic arthritis is an autoimmune disease characterized by chronic inflammation of the skin and joints. Anti-TNF drugs reduce the severity of the disease in the long term. This study compares the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in patients with psoriatic arthritis. METHODS: Direct comparison was based on a literature search of drug comparison studies, whereas indirect treatment comparison was based on phase III clinical trials with biological agents, involving similar populations and durations, and with the same outcome. ACR50 was taken as primary outcome for comparison, whereas ACR20 and ACR70 were used as secondary outcomes. Indirect comparisons were made using infliximab as the reference drug and the Bucher method. In calculating δ (the maximum acceptable difference as a clinical criterion of equivalence), use was made of half of the absolute risk reduction obtained in the meta-analysis of the clinical trials included in the indirect comparison (ARR 32%; δ: 16%). The four anti-TNF drugs were also compared in relation to the secondary outcomes and adverse effects. RESULTS AND DISCUSSION: Reported direct and indirect comparisons of the four drugs did not include golimumab, and did not yield conclusive results. Four clinical trials - one for each drug studied - were identified. The estimated differences for the primary outcome, ACR50, between infliximab and the other drugs were adalimumab (ARR 4%, 95% CI -9·5 to 17·5), etanercept (ARR 4%, 95% CI -10·5 to 18·5) and golimumab (ARR 9%, 95% CI -5·4 to 23·4). Likewise, there were no relevant differences between the drugs in relation to the secondary efficacy outcomes, except for etanercept, which was less effective in ACR70 response. For adverse reactions, there were also no significant differences except for injection site, reactions which were more frequent with etanercept, with a mean difference of 26% relative to infliximab. WHAT IS NEW AND CONCLUSION: No significant differences were found in ACR50 responses to the four drugs after 24 weeks. Injection-site reactions were more common with etanercept, but this was insufficient to invalidate the inference that clinically the four drugs can be regarded as clinically equivalent for the treatment of psoriatic arthritis.

[Classification and variability of drug assessment reports on the GENESIS group (SEFH) webpage]. / Caracterización y variabilidad de los informes de evaluación de medicamentos en la página web del grupo GENESIS de la SEFH.

OBJECTIVE: To analyse the assessment reports published on the GENESIS webpage (Group for Innovation, Assessment, Standardisation and Research in the Selection of Drugs) and assess the variability of the group's proposals to include drugs in the Formulary. METHOD: We analysed reports published by hospitals on the GENESIS webpage between 2004 and 2007. Data were collected on drugs and indications, ATC group, open or restricted access publications, hospital, and publication date. We drafted a questionnaire that would measure to what extent to what extent the 9-section model recommended by GENESIS was included in each report. For drugs with two or more reports, we analysed whether the recommendation coincided and the possible cause in the event of conflict. RESULTS: We analysed 416 reports corresponding to 185 different drug indications. 93% included 6 or more of the recommended sections, a number which increased over time. The most frequently included sections were: approved indications (92%), mechanism of action (95%), and references (86%) (percentages from 2007). Sections which had an increasing but lower percentage were: differential characteristics (60%), literature search method (40%) and conclusions with a summary of efficacy, safety and cost data (52%). 73% of which had definite recommendations, which coincided for 42 out of the 67 drugs with more than one recommendation report. CONCLUSIONS: The work carried out by the GENESIS group has enabled Spanish hospitals to share their drug assessment reports and making them more complete, although there are still some aspects that can be improved.

[Comparative study of errors in electronic versus manual prescription]. / Estudio comparativo de errores con prescripción electrónica versus prescripción manual.

OBJECTIVE: Electronic prescribing is considered a basic measure for the prevention and reduction of medications errors. The goal of this survey was to assess the incidence of errors occurring with electronic versus standard prescription. METHOD: A prospective, sequential, open-label study to assess errors with electronic prescribing as compared to traditional manual prescribing in two public hospitals in Balearic Islands. Errors regarding medication, diet and/or nursing orders were assesses along four process stages: medical prescription, pharmacy transcription/validation, nursing transcription, and dispensation. RESULTS: With manual prescription 1,576 errors/18,539 therapy orders (8.50%) were identified, whereas with electronic prescription 827 errors/18,885 therapy orders (4.38%) were detected, which represents a relative risk reduction by 48% and an absolute risk reduction by 4.12% (p < 0.0001). Pharmacy transcription/validation errors decreased (1.73 vs. 0.13%, p < 0.0001), as did nursing transcription errors (2.54 vs. 0.81%, p < 0.0001) and dispensation errors (2.13 vs. 0.96%, p < 0.0001); however, the number of prescription errors increased (2.10 vs. 2.40%, p = 0.0401). CONCLUSIONS: Electronic prescription is a powerful tool, and one that in this work was shown to decrease medication-, diet-, and nursing care-related errors in a highly significant way; however, it should be developed and maintained in order to achieve safety and effectiveness as required by drug usage.

[Compliance with hypertension treatment: 10 years of publications in Spain]. / Cumplimiento terapéutico en el tratamiento de la hipertensión: 10 años de publicaciones en España.

INTRODUCTION: Ten years of publications (1984-1993) about drug compliance in spanish hypertensive patients are presented. MATERIAL AND METHODS: A bibliography search of Medline (EBSCO CD-ROM ver 104.1, act Jul 1995), Indice Médico Español (CSIC CD-ROM, act Oct 1993) and other sources has been made. RESULTS: 39 articles have been located and 23 investigational publications have been analysed. All the publications, but one, have evaluated the compliance by an indirect method, mainly patient selfdeclaration. The degree of patient compliance determined by interviews, questionnaires or inquiries is 55.5% (IC 95%: 52.7-58.3). The patient compliance in the publications that use methods based in pill counts is 46.4% (IC 95%: 41.6-51.2). The treatment dropout is present in the 18.5% of the patients (IC 95%: 20.5-16.5). CONCLUSIONS: The drug compliance degree in Spanish patients with hypertension is low.

[Microbiological control in parenteral nutrition mixtures. Indices of contamination]. / Control microbiológico en mezclas de nutrición parenteral. Indices de contaminación.

Potential contamination of nutritional mixtures during preparation in the Pharmacy Services has led to the need for microbiological controls. In our study, we set out the techniques used in the Son Dureta Hospital between 1986 and 1991. During those six years 11,023 nutritional mixtures were prepared, and 1,714 bacteriological controls were carried out, representing 15.5% of the total. Between January 1986 and June 1989, the simple culture technique was used (culture of 10 ml of the prepared mixture). The contamination rate was 1.27%. Between July 1989 and December 1991, the double sample technique was applied, involving a culture of 10 ml of the mixture, keeping a further 10 ml for subsequent verification culture. With this technique, the contamination rate was fixed at 0.34%. The advantages and drawbacks of the techniques used are described, along with the problem of initial false positives, and a review is made of the 39 germs isolated during the period of study.

[A comparative study of 5 infusion pumps: an evaluation of their suitability for administering parenteral nutrition]. / Estudio comparativo de cinco bombas de infusión: evaluación de su idoneidad para la administración de nutrición parenteral.

To facilitate the control of administering parenteral nutrition (PN), the tendency is to replace traditional infusion equipment with infusion pumps. The aim of this study is to determine the characteristics that a pump should have for infusing PN mixtures and, based on these, to evaluate five models available on the market. The pumps evaluated, all with volumetric programming were: Becton Dickinson VIP II (Prim); Life-Care Pump Model 4 (Abbot-Shaw); Infusomat Secura 1.000 (Braun); Flo-gard (tm) 6,200 (Baxter) and IVAC-591 (Ivac). The following method was used: a) Definition of 16 basic requisites and 7 secondary requisites considered necessary in a PN pump, in accordance with the following criteria: safety, practical usage, comfort and hospital circuits. b) Review and checking of the technical reports on each pump. c) Laboratory tests simulating PN infusion, evaluating the regularity and precision of the infusion speed, and d) Subjective evaluation survey. All the pumps under study complied with the basic requisites. There were differences in the subjective evaluation, although with regard to all concepts and models a score of over 2.5 was reached in a scale of 0 to 5. The highest and lowest values with regard to regularity and precision were within the following ranges: +/- 0.6 ml/h(-)+/- 0.0 ml/h and + 3.4%(-)-1.6% respectively, and no instance of values outside the established ones was detected. The pumps only partly complied with the secondary requisites. Finally, the criteria for defining the most significant requisites was reviewed, based on the services offered by the existing pumps, as well as techniques for determining regularity and precision.(ABSTRACT TRUNCATED AT 250 WORDS)

[A prospective comparative study to assess the impact of pharmaceutical intervention in the promotion of sequential therapy with flouroquinolones]. / Estudio prospectivo y comparativo para evaluar el impacto de la intervención farmacéutica en la promoción de la terapia secuencial con fluoroquinolonas.

OBJECTIVE: To assess the impact of pharmaceutical intervention on the use of sequential therapy (ST) with fluoroquinolones. METHODS: A prospective comparative study of pharmaceutical intervention in two stages: observational stage and intervention stage for ST promotion. RESULTS: In all, 250 patients receiving intravenous therapy with fluoroquinolones (113 with levofloxacin and 137 with ciprofloxacin) were studied, with 76 and 70 patients, respectively, being eligible for a pharmaceutical intervention program to promote ST. Pharmaceutical intervention showed a decreased duration of intravenous therapy and increased duration of oral therapy for both drugs, as well as decreased medication-related costs, all in a statistically significant manner. DISCUSSION: ST promotion provides an opportunity to expand the role of hospital pharmacists and to optimize fluoroquinolone-based therapy, which results in decreased intravenous treatments and provides a more cost-effective option.

[A prospective randomized study of sulphonylureas therapeutic interchange in patients with type 2 diabetes mellitus]. / Estudio prospectivo y aleatorizado de intercambio terapéutico de sulfonilureas en pacientes con diabetes mellitus tipo 2.

OBJECTIVE: To clinically assess effectiveness of therapeutic interchange from glibenclamide to gliclazide in the hospital setting. METHODS: An open-label prospective, randomized study with two groups of patients: a reference group (patients still receiving their previous outpatient regimen of glibenclamide) and an interchange group (patients with gliclazide substituted for glibenclamide according to a hospital-approved interchange protocol). The efficacy endpoint used was blood glucose at 3 and 6 days post-intervention. A patient with blood glucose < 200 mg/L was considered clinically controlled, and blood glucose changes < or > 30 mg/dL were considered significant. RESULTS: One hundred and sixteen patients were randomized. Blood glucose on the day before the intervention was 177.9 mg/dL +/- 63.4 in the reference group versus 171.3 mg/dL +/- 52.1 in the interchange group (p = 0.92). Mean blood glucose during the first 3 days post-intervention was 156.1 mg/dL +/- 47.5 and 177.7 mg/dL +/- 36.0 (p = 0.14) in the reference and interchange groups, respectively; and mean values for the first 6 days post-intervention were 142.1 mg/dL +/- 36.0 and 172.8 mg/dL +/- 28.2, respectively (p = 0.01). The overall analysis of blood glucose levels showed a better control in the reference group versus baseline values, which was not seen in the interchange group, where blood glucose remained stable and similar to baseline. In no case were 3-day and 6-day blood glucose mean levels above 200 mg/dL, which may be considered acceptable within the hospital setting. CONCLUSIONS: Therapeutic interchange may be safely performed with no clinical impairment, but better controls were achieved in the reference group.

[Indirect comparisons in drug assessment reports on the GENESIS group (SEFH) webpage]. / Comparaciones indirectas en los informes de evaluación de medicamentos en la web del grupo GENESIS de la SEFH.

OBJECTIVE: Quantify use of indirect comparisons (IC) in drug evaluation reports published on the GENESIS Group web page for new drug assessment, standardisation, and drug selection research. METHOD: Retrospective study of drug reports written between 2008 and 2009. DATA COLLECTED: presence of an active comparator and details from any direct and indirect comparative studies included. RESULTS: An active comparator was present in 95% of the 337 analysed reports; 50% included a direct comparative study vs comparator. In 114 reports (34%), an IC was used; 69% of the ICs were made by the report author. Most ICs were narrative and none were adjusted. An IC could have been made in an additional 16% of the cases and possibly in 24% more. CONCLUSIONS: Most evaluated drugs have an active comparator but studies comparing them directly are not as common. ICs could be included in more reports along with quality control criteria.

Variability in activity and results from drug assessments by pharmacy and therapeutics committees in Spanish hospitals.

OBJECTIVE: To quantify the Spanish Pharmacy and Therapeutics Committees (P&TC) activity with regard to assessing and selecting drugs and describing variability in decisions made to include them. METHOD: Descriptive, cross-sectional study based on a questionnaire aimed to 513 hospitals with more than 75 beds. We included questions referring to the P&TC resolutions, the therapeutic positioning and assessment reports. Recruitment was carried out between November 2007 and January 2008. Variability among P&TC conclusions were presented in five categories or levels of coincidence. RESULTS: One hundred and seventy-five hospitals participated, with a response rate of 34% (54% of beds). The mean (SD) number of drug-indications assessed per hospital was 10.35 (7.45). The proportion of assessments that conclude with drug inclusion or rejection was 75.3 and 21.4%, respectively. 16.2% concluded with therapeutic equivalence. Conditions for use were established for 64% of them, and 33% were included in a clinical guide. With regard to variability, 81.0% of assessments coincided with the conclusion to include or reject the drug. A contradictory decision was made for 19.0%. CONCLUSIONS: Drug assessment and selection activity in hospitals involve an amount of work. The proportion of drugs approved is similar in different types of hospitals. There is extensive variability as regards deciding upon inclusion and is similar to studies conducted in other countries. They indicate that a standardising methodology would be recommendable.

Developing a search engine for pharmacotherapeutic information that is not published in biomedical journals.

OBJECTIVE: To identify publishers of pharmacotherapeutic information not found in biomedical journals that focuses on evaluating and providing advice on medicines and to develop a search engine to access this information. METHODS: Compiling web sites that publish information on the rational use of medicines and have no commercial interests. Free-access web sites in Spanish, Galician, Catalan or English. Designing a search engine using the Google "custom search" application. RESULTS: Overall 159 internet addresses were compiled and were classified into 9 labels. We were able to recover the information from the selected sources using a search engine, which is called "AlquimiA" and available from http://www.elcomprimido.com/FARHSD/AlquimiA.htm. CONCLUSIONS: The main sources of pharmacotherapeutic information not published in biomedical journals were identified. The search engine is a useful tool for searching and accessing "grey literature" on the internet.

[Program for the substitution of therapeutic equivalents in the hospital setting]. / Programa para la sustitución de equivalentes terapéuticos en el medio hospitalario.

BACKGROUND: A Program of Therapeutic Equivalents (TEP) is here reported which was elaborated and is currently in force at a third level university teaching hospital. MATERIALS AND METHODS: Therapeutic equivalents were selected within the same pharmacologic group on the basis of approved indications and both efficiency and safety data. RESULTS: TEP considers: a) the substitution of drugs which are considered therapeutic equivalents; b) withdrawal of drugs which have not proved efficiency or are of no interest for inpatients; c) continuation of therapies when changes are not advisable, and d) indistinct use of homologous drugs. From August 1998 up to April 1999, TEP was applied in 505 occasions; it was accepted in 499 (99%) and rejected in 6 (1%). DISCUSSIONS: The substitution of therapeutic equivalents should be viewed in the context of selecting the most appropriate drugs to be used in the hospital setting. TEP should be a consensus document and supervised by the Pharmacy and Therapeutics Commission.

Comparaciones indirectas en los informes de evaluación de medicamentos en la web del grupo GENESIS de la SEFH / Indirect comparisons in drug assessment reports on the GENESIS group (SEFH) webpage

Objetivo: Cuantificar el uso de comparaciones indirectas (CI) en los informes de evaluación de medicamentos publicados en internet por el Grupo de Evaluación de Novedades, Estandarización e Investigación en Selección de Medicamentos (GENESIS).Método Estudio retrospectivo de los informes redactados en 2008-2009. Registro de la existencia de comparadores y características de los estudios comparativos directos e indirectos incluidos. Resultados En el 95% de los 337 informes analizados existe un comparador activo, en el 50% hay un estudio frente a éste. En 114 informes (34%), se referencia una CI, el 69% elaborada por el autor del informe. La mayoría fueron CI narrativas, ninguna ajustada. En los casos sin CI podría haberse realizado en el 16% y era dudoso en el 24%.ConclusionesMuchos medicamentos tienen comparador pero no estudios directos frente a éste, las CI deberían incorporarse en los informes en mayor medida y con criterios de calidad. (AU)

Objective: Quantify use of indirect comparisons (IC) in drug evaluation reports published on the GENESIS Group web page for new drug assessment, standardisation, and drug selection research. Method: Retrospective study of drug reports written between 2008 and 2009. Data collected: presence of an active comparator and details from any direct and indirect comparative studies included. Results: An active comparator was present in 95% of the 337 analysed reports; 50% included a direct comparative study vs comparator. In 114 reports (34%), an IC was used; 69% of the ICs were made by the report author. Most ICs were narrative and none were adjusted. An IC could have been made in an additional 16% of the cases and possibly in 24% more. Conclusions: Most evaluated drugs have an active comparator but studies comparing them directly are not as common. ICs could be included in more reports along with quality control criteria (AU)

Comparaciones indirectas, respuesta de los autores / Indirect comparisons, author response

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