Biological treatments for moderate-to-severe psoriasis: indirect comparison.

WHAT IS KNOWN AND OBJECTIVE: Psoriasis is a chronic skin disease for which there is an increasing range of treatment options. Biological agents (ustekinumab, adalimumab, infliximab and etanercept) are indicated for moderate-to-severe plaque-type psoriasis in adults who fail to respond to, have a contraindication to, or are intolerant to other systemic therapies including cyclosporine, methotrexate and PUVA Unfortunately, with new drugs, the pivotal trials leading to their licensing are often placebo-controlled trials rather than comparative trials vs. established therapies. Therefore, inference on comparative effectiveness of the newer agents must be derived indirectly, through estimation of effects of the new agents vs. a common comparator. The objective of this study is to compare the relative efficacy of the biological agents through a systematic review of the indirect clinical trial evidence. METHODS: A systematic literature search was performed for clinical trials of biological agents in psoriasis. Pivotal, randomized, double-blind, controlled (placebo) trials using intention-to-treat analysis were selected for detailed analysis. Trials must include PASI 75 as a primary end point. The indirect comparison was performed using the method of Bucher adjusted with the ITC calculator (Indirect Treatment Comparisons of the Canadian Agency for Drugs and Technologies in Health), etanercept being the reference drug. We defined delta value for therapeutic equivalence as a difference in the efficacy of 25% among the different treatment options. RESULTS AND DISCUSSION: Fourteen studies (four for ustekinumab, three for adalimumab, three for infliximab and four for etanercept) were included. The indirect comparison results reveal that ustekinumab, adalimumab and infliximab were statistically superior to etanercept with an absolute risk difference for PASI 75 of 12% (95% CI = 5·9-18%), 11% (95% CI = 5·3-16·7%) and 24% (29·7-18·3%) respectively. However, in all situations, the 95% confidence interval does not achieve clinical relevance as no delta exceeds the previously set value (25%). WHAT IS NEW AND CONCLUSION: Ustekinumab, adalimumab, infliximab and etanercept can be regarded as clinical equivalents for the treatment of psoriasis. Choice between these agents therefore depends on their relative safety profiles, individual contra-indications and cost effectiveness.

Association between anticholinergic activity and xerostomia and/ or xerophthalmia in the elderly: systematic review.

PURPOSE: The aim of this work was to investigate the association between anticholinergic burden or anticholinergic drug use and xerostomia and/or xerophtalmia in elderly through a systematic review of the published literature. METHODS: A search was carried out in 3 databases (CINAHL, Embase and Pubmed). Studies conducted in people ≥65 years of age, who took anticholinergic medications, and measured the association between the anticholinergic burden or the use of these medications with the prevalence of xerostomia and / or xerophthalmia, published up to August 2022, were selected. Studies published in languages other than Spanish and/or English were excluded. RESULTS: One thousand two hundred eleven articles were identified, 10 were selected for this review: six cross-sectional studies, two cohorts, one case-control and one randomized controlled clinical trial. A total of 3535 patients included in the different studies were studied. The most used scales were the Anticholinergic Drug Scale (ADS) and the Anticholinergic Risk Scale (ARS). Four articles studied the relationship between the use of anticholinergic medication and the prevalence of xerostomia and / or xerophthalmia, finding a positive relationship with xerostomia in all of them. Another 6 measured the relationship between anticholinergic burden and xerostomia and / or xerophthalmia. Four found a positive relationship between anticholinergic burden and xerostomia and/or xerophthalmia. CONCLUSIONS: Our findings suggest a clear relationship between the use of anticholinergic drugs or anticholinergic burden and the presence of xerostomia. This relationship was less conclusive in the case of xerophthalmia.

[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.

Consensus method to update the GINF formulary request form.

OBJECTIVE: To update the Guideline for the Introduction of New Drugs in the Formulary (GINF form) using the RAND/UCLA appropriateness method, which combines the best available evidence and an expert panel's judgement. STUDY DESIGN/METHODS: Two procedures were employed to detect where improvements could be made to the former versions of the request form and to transform them into concrete scenarios, found from a telephone survey with GINF form users, and a structured review of the scientific literature. The list of scenarios was later assessed by an expert panel. In a series of successive rounds, the rest of the research team critically assessed the expert panel's result, applying a score. RESULTS: A total of 52 improvement proposals were registered; 31 of them dealt with the form structure and the remaining 21 referred to the form process. Six formulary request forms were selected from the literature review. The final version included 24 assessed scenarios mainly addressing clinical trials' validity, qualitative assessment and local implications of the requested drug. CONCLUSIONS: A new version of the GINF form has been developed. Much improvement has been made based on the guide users' opinion, available evidence and similar experiences that have been carried out internationally. The whole process has been subject to the experts' opinion following a contrasted, consensus methodology: RAND/UCLA appropriateness method.

[Analysis of the selection process for new drugs in a tertiary hospital 2004-2007]. / Análisis del proceso de selección de nuevos medicamentos en un hospital terciario. Años 2004-07.

OBJECTIVE: The purpose of this study is to describe the structure of the CFyT, the Pharmacy and Therapeutics Committee, and a tertiary hospital's selection process for new drugs. MATERIAL AND METHODS: All annals of the P&TC and the New Drug Incorporation Guides (GINF) to incorporate new drugs received at Hospital Virgen del Rocío between 2004 and 2007 were reviewed. We carried out a descriptive study which collected variables having to do with the drug (drug type, type of register, route of administration and legal category), the petitioner (responsible division, professional category and request type) and the result of the evaluation (final decision, elapsed time between the request and the decision). RESULTS: Of the 72 requested drugs, 45 (62.5%) were approved: six as equivalent treatments, 36 (80%) with specific recommendations, and three (4.2%) with no restrictions. Twelve drugs (81.1%) were not included due to insufficient evidence of their effectiveness compared with the current treatment. The most frequently-requested drug type was the antineoplastics, most commonly requested by Oncology and Haematology divisions. We highlight the fact that many of the petitioners included clinical trials (97.2%) and data referring to costs (84.7%). CONCLUSIONS: There is a high level of compliance with the GINF guide in our centre, which guarantees that the P&TC's final decision is based on scientific evidence.

[Quality of interaction database management systems]. / Calidad estructural de las bases de datos de interacciones.

OBJECTIVE: To identify drug interaction databases (DID) and assess the quality of their structures. METHOD: A search was made of the literature for DID and a series of exclusion and structural quality criteria were defined (at least four quality criteria: Classification according to severity, classification according to level of evidence, bibliographical reference data, description of clinical management and 11 criteria used for weighting). The level of compliance of every DID with the criteria defined was analysed, together with the level of compliance of each criteria in each DID. RESULTS: A total of 54 DID were identified, 30 of which complied with exclusion criteria and 15 of which did not meet the minimum criteria. The rest of the criteria were evaluated in nine DID: Bot-plus and Medinteract (100 %), SEFH Guide, Lexi-interact and Medscape (89 %), Hansten (83 %), Micromedex and Stockley (78 %), Drug Interactions Facts (68 %). Ninety-two per cent of the DID describe the mechanism of action, 87 % classify the information according to the active ingredient, 75 % do not state they have any conflict of interest, classify according to level of severity, have electronic format and are easy to search. A total of 67 % are specific DID, 62 % are classified according to level of evidence, contain bibliographical references and describe clinical management. CONCLUSIONS: A third of the DID comply with the minimum criteria. Differences were observed in the level and compliance criteria among Spanish and foreign DID. Some of the main DID used as references in the bibliography have significant structural defects: no web presentation, no multi-check function and others.

[Implementation of the guidelines for the introduction of new drugs (GINF) in Andalusian hospitals]. / Implantación de la guía para la incorporación de nuevos fármacos (GINF) en los hospitales andaluces.

OBJECTIVE: To measure the level of implementation of the GINF (guidelines for the introduction of new drugs) in Andalusian hospitals, describe the characteristics of this implementation and analyse if any of the hospital s dependent variables could influence these characteristics. METHOD: A telephone survey was carried out in the hospitals included in the Department of Health list. The survey consisted of 11 closed questions on different variables in the hospital and the GINF use profile, and an open question about the improvements carried out and proposals for improvement. The results were analysed according to the type of hospital (category, training, geographical location) in order to detect possible differences. RESULTS: A target population of 31 hospitals was identified. The survey was carried out in 29 of these; the level of implementation was 96.5% in the responding hospitals. 23 hospitals used the GINF for 100% of drugs, 6 had carried out local modifications and 80% made proposals for improvement. Significant differences were found in the implementation of the GINF according to resident/intern pharmacist training (p = 0.049), the geographical location (p = 0.004) and the hospital category (p < 0.001). CONCLUSIONS: The GINF have been implemented in almost all public Andalusian hospitals as the guidelines for requesting new drugs. Very few local modifications have been carried out to the guidelines, although numerous proposals for improvement have been made. Differences in use have been identified (No. of drugs, different versions) according to the hospital characteristics (location, training and complexity classification). They are considered a useful tool and influence the drug selection process, in particular in training hospitals with a higher classification.

[Evaluation of drug treatment of myocardial infarction in public hospitals of Andalusia. GAUME (Andalusian Group for performance of Studies on Drug Utilization)]. / Evaluación del tratamiento farmacológico del infarto de miocardio en los hospitales públicos de Andalucía. GAUME (Grupo Andaluz para la realización de Estudios de Utilización de Medicamentos).

BACKGROUND: The management of patients with acute myocardial infarction (AMI) has changed over the last decade. The aim of this study was to evaluate the pharmacologic treatment of AMI in the clinical practice, with special emphasis in thrombolytic therapy. MATERIAL AND METHODS: Prospective drug utilization survey, collecting data from 26 hospitals belonging to the Andalusian Health Service, Spain, during one month period. Pharmacologic treatment in the first 24 h was obtained. RESULTS: Out of 379 patients recruited, 52.8% received thrombolytic therapy, although another 19% could have obtained some benefit from that therapy. Alteplase was the most frequently used thrombolytic (65.5%). The regimen prescribed was mainly that followed in GUSTO Study (45.8%) or double bolus (43.5%). In a high percentage of patients the thrombolytic selection was not made according to the results of the literature. Women and patients older than 75 years were less likely to receive thrombolytic therapy. There was a high utilization of aspirin (89.7%), nitrates (84.4%) and heparin (83.6%). CONCLUSIONS: Thrombolytic therapy was prescribed in a higher percentage of patients than is reported in other trials. In spite of that, thrombolytics should have been used in more patients. As alteplase does not have a definitive benefit over streptokinase, protocol is needed when selecting a thrombolytic agent.

[An evaluation of the effect of light on a commercial solution of amino acids for parenteral nutrition]. / Valoración del efecto de la luz sobre una solución comercial de aminoácidos para nutrición parenteral.

There are few studies on the stability of amino acids in solutions prior to mixing for parenteral nutrition, and even few studies which evaluate the contribution of light to their deterioration. The present study was carried out with the aim of becoming familiar with this parameter of stability in the working conditions of our Pharmacy Service. Two batches of Aminoplasmal L-10 were taken, one of which was subjected to direct low intensity sunlight and the other was maintained in the dark, as a control batch, for between 3-6 months. At the end of this time, complete aminograms were performed by ionic interchange chromatography. The measurements of concentrations of each amino acid were obtained for each batch. A Student T test was used to show that there were no significant differences between them after both 3 and 6 months. It was therefore concluded that the amino acid solution we had tested was maintained stable under the light exposure conditions of our Service after 6 months.

[Interstitial cystitis: drug therapy]. / Cistitis intersticial: tratamiento farmacológico.

The present job reviews the etiology, clinical presentation, diagnostic and treatment of interstitial cystitis. An exhaustive revision is made of all the possibilities of pharmacological treatment with a special mention to the two major drugs: dimethylsulfoxide and pentosampolysulphate. A critical judgement of existing clinical trials is made. The conclusion indicates the need of more controlled experimental work in the future to allow a more objective determination of the most appropriate and effective therapy for these patients.

Reliability of a questionnaire for pharmacological treatment appropriateness in patients with multiple chronic conditions.

BACKGROUND: The original Medication Appropriateness Index was validated for elderly and polymedicated patients, both in hospital and outpatient contexts. However, no studies have applied this questionnaire in patients with multiple chronic conditions. The objective of this study is to assess the reliability of a modified Medication Appropriateness Index questionnaire in a population of patients with multiple chronic conditions. METHODS: We selected patients with multiple chronic conditions who were included in an integrated care project conducted at the Hospital Universitario Virgen del Rocío. To determine inter-observer reliability, each professional (internist or hospital pharmacy specialist) applied the questionnaire under the same conditions and with the same resources. To determine intra-observer reliability, each physician applied the tool at baseline and two months later. We measured inter- and intra-observer reliability using the kappa coefficient. The proportion of overall agreement was also determined. RESULTS: We obtained a weak overall kappa (k=0.38) for inter-observer reliability and moderate (k=0.52) and very good (k=0.84) values for intra-observer reliability of the internist and specialist in hospital pharmacy, respectively. The proportion of overall agreement is very high in all three situations: 96%, 98%, and 99%, respectively. CONCLUSIONS: Despite its limitations, the Medication Appropriateness Index questionnaire modified by our group can be used, as a reliable method, to assess the appropriateness of pharmacotherapy in patients with multiple chronic conditions.

Assessment of new drugs in a tertiary hospital using a standardized tool.

OBJECTIVE: To describe the profile of new drugs evaluated by the Pharmacy and Therapeutics committee in a tertiary hospital using a standardized tool, the Guideline for the Introduction of New Drugs in the Formulary (GINF form), as main objective. MATERIALS AND METHODS: Retrospective observational study of drugs was assessed during 2008-2011. Variables related to the drug, the request, and the result of the evaluation were collected based on information contained in the GINF form and in the assessment reports. RESULTS: 63 of 75 assessed drugs (84%) were included in the hospital formulary. Only one drug (1%) was included without any restrictions. The rest of them were included as therapeutic equivalents (23%) or under specific recommendations (61%). Half of the drugs (6) not included had insufficient evidence of effectiveness compared with current treatments. Haematology and Medical Oncology were found to be the most active medical services in the application process. There was a high prevalence of drugs that had more than one advanced clinical trial (phase III and/or phase IV). Furthermore, 28% of assessed drugs were associated with a financial burden of more than ?10,000 per year for our hospital. Highquality information was provided by applicants to the P&T committee for drugs that were finally included. However, the relationship between the information provided to the P&T committee and its decision was not statistical significance. CONCLUSION: The requests received were primarily related to drugs intended for parenteral use and most of them were antineoplastic drugs. The medical departments most heavily represented were Haematology and Oncology.

Objetivo: Describir las características de los nuevos fármacos evaluados por la Comisión de Farmacia y Terapéutica (CFyT) en un hospital terciario mediante el empleo de una herramienta normalizada, la Guía para la valoración de Inclusión de Nuevos Fármacos, como objetivo principal. Material y métodos: Estudio observacional retrospectivo de aquellos fármacos evaluados en el periodo 2008-11. Fueron recogidas variables relativas al fármaco, a la solicitud y al resultado final de la evaluación mediante la información contenida en las guías GINF y en los informes finales de evaluación. Resultados: De los 75 medicamentos evaluados, 63 (84%) fueron incluidos en la Guía Farmacoterapéutica del Hospital. Únicamente 1 (1,3%) lo fue sin ningún tipo de restricción. El resto fueron incluidos como equivalentes terapéuticos (21,3%) o bajo recomendaciones específicas (61,3%). La mitad de los fármacos no incluidos (6) presentaban insuficiente evidencia respecto a su eficacia frente a los tratamientos habituales. Hematología y Oncología Médica se encontraron entre los servicios médicos más activos en la solicitud. Se observó un alto porcentaje de fármacos que disponían de más de un ensayo clínico en fase avanzada (III y/o IV). Por otra parte, el 28% de los fármacos evaluados se relacionaron con un impacto financiero superior 10.000 ??anuales. Las guías GINF proporcionadas por los solicitantes a la CFyT se caracterizaron por la alta calidad de la información contenida en ellas. Sin embargo, la relación entre la información proporcionada a la CFyT y la decisión final de la misma no fue estadísticamente significativa. Conclusiones: Las solicitudes recibidas pertenecieron principalmente a fármacos de administración parenteral, siendo la mayor parte de ellos antineoplásicos. Los servicios médicos más intensamente representados fueron Hematología y Oncología.

[Off-label approval of drug use in a tertiary hospital]. / Autorización de usos de medicamentos fuera de indicación en un hospital de tercer nivel.

BACKGROUND AND OBJECTIVE: The Pharmacy and Therapeutics Committee (PTC) evaluates the requests for off-label uses with an abbreviated report format. The aim of this study is to perform a descriptive analysis of this activity and to study the rate of approvals. MATERIAL AND METHODS: A descriptive study was performed on the PTC reports in a tertiary hospital between September 2009 and April 2011. The type of drug by treatment group and by type of dispensing, indication and requesting department was analysed. The final decision adopted was studied as the primary outcome, and the percentage of requests approved according to the characteristics of the drug evaluated, indication requested, alternatives used, evidence and cost, as secondary outcomes. RESULTS: A total of 51 applications were analysed, of which 60.8% were drugs for hospital use and 54.9% cytostatic. The most requested indications were the onco-haematological (43.2%) and autoimmune (35.3%). Haematology was the department that made most requests (11 requests with 72.7% approved), Oncology and Paediatrics (both with 10 requests, with 50% approved). Almost two-thirds (60.8%) of the requests were approved. Of those that were not approved, 11 had not used up the therapeutic alternatives, and 8 had no evidence. Just under half (47.1%) of the drugs requested had a cost/patient between 10,000-100,000 euros,of which 58.3% were approved (cost per course of treatment if it had a defined period, or cost of treatment per year for chronic treatment). CONCLUSION: There is an increase in the activity of the PTC that is growing over the years. Most applications focus on drugs for hospital use and cytostatic drugs by Onco-haematology. There is a high rate of approval by the PTC, and high variability in the percentage of approval depending on the department and the evidence of use. The difference between approved and unapproved requests followed a logic of cost-effectiveness.

[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.

[Health care models for patients with multiple chronic conditions and the role of the hospital pharmacy/the hospital pharmacist]. / Modelos de atención al paciente pluripatológico y el papel de la farmacia hospitalaria.

INTRODUCTION: Managing care for patients with chronic conditions currently represents one of the greatest challenges to health care systems. As a subgroup of these patients, those with multiple chronic conditions are at greater risk for death or disability, and they consume more resources. They are characterized by the coexistence of two or more chronic illnesses lasting a year or longer which require ongoing medical attention and/or interfere with their daily activities. For these polypathological patients pharmaceutical care would be of special benefit, thus, their needs should be a priority objective for hospital pharmacy. OBJECTIVE: To increase awareness of this type of patients and the characteristics of the principal approaches and health care models proposed to improve chronic disease management, as well as to emphasize the urgency for hospital pharmacists to join these models, and to present various activities that pharmacists might carry out as an integral part of these approaches. RESULTS: Numerous models exist internationally, including the Chronic Care Model and the Kaiser Permanente pyramid of risks. In our country a growing number of initiatives has culminated in the recent Seville Declaration. For the hospital pharmacy, caring for the chronically ill patient following a model that is multi-professional, cooperative, integral, and patient centered, is an enormous task. Pharmacy departments and the Spanish Society of Hospital Pharmacy should reorient their strategies for pharmaceutical care, training, and research. Of special interest are those activities designed to improve adherence, adequacy, and continuity in treatments, all the while emphasizing active patient participation.

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.