Retrospective analysis of patients with advanced or metastatic gastric cancer in Colombia.

Aims: To assess patient and disease characteristics, treatment patterns, and associated costs in patients with advanced or metastatic gastric cancer (A/MGC) in Colombia, in both the public and private hospitals. Materials and methods: A total of 145 patients who had received first-line chemotherapy treatment (platinum analog and/or a fluoropyrimidine) and were followed for at least 3 months after the last administration of a first-line cytotoxic agent were eligible for inclusion. Case-report forms were elaborated based on the patients' medical records from three Colombian hospitals. Estimates of treatment costs were calculated using unit costs from the participating hospitals. Results: Of the 145 patients, more than half (64.83%) were male, 79.56% were diagnosed with metastatic stage IV disease (mean age = 58.14 years). Prior to MGC diagnosis, 31.71% of the patients being operated on received a total gastrectomy; 66.9% of the patients received a doublet therapy, of which 5-fluorouracil (5-FU) in combination with cisplatin was the standard treatment (14%), followed by combination with leucovorin (12%). Only around 10% of the patients responded to first-line treatment. Out of 41.38% of the patients who received a second-line treatment, 71.67% were still administered a platinum analog and/or fluoropyrimidine. During the follow-up period, 52% of the patients progressed and 20% achieved stable disease. Best supportive care mostly consisted of outpatient visits after last line-therapy (72.41%), palliative radiotherapy (18.6%), and surgery (37.2%). Limitations and conclusions: Gastric cancer is one of the main causes of cancer-related death in Colombia, as most of the patients are diagnosed at an advanced stage, when prognosis is poor. Treatment patterns are highly heterogeneous. Second-line treatments were mostly initiated with paclitaxel, capecitabine, irinotecan, or cisplatin.

Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis.

OBJECTIVE: The objective was to determine if dose reduction is non-inferior to full-dose TNFi to maintain low disease activity (LDA) in patients already in remission with TNFi, in axial spondyloarthritis. METHODS: Randomized, parallel, non-inferiority, open-label multicentre clinical trial. Patients were eligible if they had axial spondyloarthritis and had been in clinical remission for ≥ 6 months with any available TNFi (adalimumab, etanercept, infliximab, golimumab) at the dose recommended by product labelling. Patients were randomized by automated central allocation to continue the same TNFi dose schedule, or to reduce the dose by roughly half according to the protocol. The main outcome was the proportion of subjects with LDA after 1 year. Serious adverse reactions or infections were recorded. RESULTS: The trial stopped due to end of the funding period, after 126 patients were randomized; 113 patients (84.1% male, mean age (SD) 45.6 (13.0) years) were included in the main per-protocol subset. Non-inferiority was concluded for LDA at 1 year (47/55 (83.8%) patients in the full-dose and 48/58 (81.3%) patients in the reduced-dose arm, adjusted difference (95% CI) - 2.5% (- 16.6% to 11.7%)). Serious adverse reactions or infections were reported in 7/62 patients (11.3%) assigned to full dose and 2/61 patients (3.3%) assigned to reduced dose (p value = 0.164). CONCLUSION: In patients with ankylosing spondylitis in clinical remission for at least 6 months, dose reduction is non-inferior to full TNF inhibitor doses to maintain LDA after 1 year. Serious adverse events may be less frequent with reduced doses. TRIAL REGISTRATION: EU Clinical Trials Registry, EudraCT 2011-005871-18 and ClinicalTrials.gov, NCT01604629 .

Should clinically meaningful outcomes in cancer be based on individual survival rather than median overall survival?

AIM: To assess whether the use of median overall survival to define clinically meaningful outcomes in the area of oncology could yield different decisions compared with those obtained with a more realistic measure such as individual survival. METHODS: Two scenarios that offered equivalent health gains/money spent were presented: 'median overall survival' scenario (new treatment provided small clinical benefits for the average population) and 'individual survival'scenario (new treatment provided substantial clinical benefits for a small percentage of the patients and no benefits for the rest). Responses from both scenarios were compared. RESULTS: Responses between the two scenarios were different for oncologists, healthcare policy makers and patients (p < 0.05). 'Individual survival' scenario obtained higher percentage of positive answers compared with 'median overall survival'. CONCLUSION: Expressing the benefits of new oncologic treatments in terms of 'individual survival' may yield to different healthcare decisions compared with the widely used median overall survival.

Perceptions of Oncologists, Healthcare Policy Makers, Patients and the General Population on the Value of Pharmaceutical Treatments in Oncology.

INTRODUCTION: The purpose of this study was to explore the main factors explaining the relative weight of the different attributes that determine the value of oncologic treatments from the different perspectives of healthcare policy makers (HCPM), oncologists, patients and the general population in Spain. METHODS: Structured interviews were conducted to assess: (1) the importance of the attributes on treatment choice when comparing a new cancer drug with a standard cancer treatment; (2) the importance of survival, quality of life (QoL), costs and innovation in cancer; and (3) the most worrying side effects related to cancer drugs. RESULTS: A total of 188 individuals participated in the study. For all participants, when choosing treatments, the best rated characteristics were greater efficacy, greater safety, treatment adaptation to patients' individual requirements and the rapid reincorporation of patients to their daily activities. There were important differences among participants in their opinion about survival, QoL and cost. In general, oncologists, patients, and the general population gave greater value to gains in QoL than healthcare policy makers. Compared to other participants healthcare policy makers gave greater importance to the economic impact related to oncology treatments. CONCLUSIONS: Gains in QoL, survival, safety, cost and innovation are perceived differently by different groups of stakeholders. It is recommended to consider the perspective of different stakeholders in the assessment of a new cancer drugs to obtain more informed decisions when deciding on the most appropriate treatment to use. FUNDING: Eli Lilly & Co, Madrid (Spain).

Do new cancer drugs offer good value for money? The perspectives of oncologists, health care policy makers, patients, and the general population.

BACKGROUND: In oncology, establishing the value of new cancer treatments is challenging. A clear definition of the different perspectives regarding the drivers of innovation in oncology is required to enable new cancer treatments to be properly rewarded for the value they create. The aim of this study was to analyze the views of oncologists, health care policy makers, patients, and the general population regarding the value of new cancer treatments. METHODS: An exploratory and qualitative study was conducted through structured interviews to assess participants' attitudes toward cost and outcomes of cancer drugs. First, the participants were asked to indicate the minimum survival benefit that a new treatment should have to be funded by the Spanish National Health System (NHS). Second, the participants were requested to state the highest cost that the NHS could afford for a medication that increases a patient's quality of life (QoL) by twofold with no changes in survival. The responses were used to calculate incremental cost-effectiveness ratios (ICERs). RESULTS: The minimum improvement in patient survival means that justified inclusions into the NHS were 5.7, 8.2, 9.1, and 10.4 months, which implied different ICERs for oncologists (€106,000/quality-adjusted life year [QALY]), patients (€73,520/QALY), the general population (€66,074/QALY), and health care policy makers (€57,471/QALY), respectively. The costs stated in the QoL-enhancing scenario were €33,167, €30,200, €26,000, and €17,040, which resulted in ICERs of €82,917/QALY for patients, €75,500/QALY for the general population, €65,000/QALY for oncologists, and €42,600/QALY for health care policy makers, respectively. CONCLUSION: All estimated ICER values were higher than the thresholds previously described in the literature. Oncologists most valued gains in survival, whereas patients assigned a higher monetary value to treatments that enhanced QoL. Health care policy makers were less likely to pay more for therapeutic improvements compared to the remaining participants.

Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

BACKGROUND: Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. METHODS/DESIGN: To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. DISCUSSION: The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. TRIAL REGISTRATION: EudraCT 2011-005871-18 (21 December 2011).

Drug utilization and off-label drug use in Spanish pediatric gastroenterology outpatients.

BACKGROUND AND OBJECTIVES: The clinical use of medicines outside the conditions authorized in their Summary of Product Characteristics (SPC) (off-label use) is a common practice in pediatrics. The aim of the present study was to describe and quantify the medicines received by children attended in the pediatric gastroenterology department, their off-label use, and compliance with accepted rules for said use. METHODS: A retrospective observational study was performed on all of the patients who had their first consultation in pediatric gastroenterology between January 1 and October 31, 2010. All of the clinical information and medicines prescribed were analyzed. Off-label use was defined as the use of medicines in indications not included in the officially approved SPC or in ages not included or recommended in the SPC as well as the use of doses, intervals, or administration routes different from those considered in the SPC. RESULTS: A total of 695 patients (52.8% male) were included, 48.2% younger than 2 years. Two-hundred seven patients (29.8%) received 331 prescriptions. The most commonly used medicines were anti-H2 and proton pump inhibitors. Of all the prescriptions, 33.2% were considered off-label, and up to 47.3% of the prescribed patients had at least 1 medicine under off-label conditions. The medical records contained no documentation on information given to the parents regarding off-label use. CONCLUSIONS: The study found a high percentage of off-label use of medicines in the Pediatric Gastroenterology outpatient setting, especially in children younger than 2 years. Several initiatives were derived from the present study and implemented in our hospital.

Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema.

BACKGROUND: Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology. METHODS: A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garments). The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment.The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less attractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image). DISCUSSION: The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT01152099.

Antiviral efficacy of NS3-serine protease inhibitor BILN-2061 in patients with chronic genotype 2 and 3 hepatitis C.

BILN-2061, a specific and potent peptidomimetic inhibitor of the HCV NS3 protease, has recently been shown to markedly lower serum hepatitis C virus (HCV)-RNA levels in patients chronically infected with HCV genotype 1 in three 2-day proof of principle studies. The aim of the current study was to assess the antiviral efficacy of BILN-2061 in patients with genotypes 2 and 3 HCV infection. The antiviral efficacy, pharmacokinetics, and tolerability of 500 mg twice-daily BILN-2061 given as monotherapy for 2 days in 10 patients chronically infected with non-genotype 1 HCV (genotype 2: n = 3; genotype 3: n =7) and minimal liver fibrosis (Ishak score 0-2) were assessed in a placebo-controlled (placebo n = 2), double-blind pilot study. HCV-RNA levels decreased by > or =1 log(10) copies/mL in 4 of 8 patients treated with BILN-2061. One patient showed a weak response of <1 log(10) copies/mL. Three of 8 treated patients showed no response. There was no correlation between baseline viral concentration or genotype and response. BILN-2061 exhibited good systemic exposure after oral administration and was well tolerated. In conclusion, the antiviral efficacy of the HCV serine protease inhibitor BILN-2061 is less pronounced and more variable in patients with HCV genotype 2 or 3 infection compared with previous results in patients with HCV genotype 1. A lower affinity of BILN-2061 for the NS3 protease of genotypes 2 and 3 HCV is most likely a major contributor to these findings.

Estudios farmacogenéticos: guía de evaluación para Comités Éticos de Investigación Clínica. Protocolo y hoja de información al paciente (II) / Pharmacogenetic studies: evaluation guidelines for research ethics committees. Study protocol and patient information sheet (II)

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Comités éticos de investigación clínica y 'dictamen único' de los ensayos clínicos multicéntricos / Unified report from committes on Ethics and Clinical Investigations in multicenter trials

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Estudios farmacogenéticos: guía de evaluación para comités éticos de investigación clínica. Fundamentos científicos y marco legal (I) / Pharmacogenetic studies: evaluation guidelines for research ethics committees. Scientific background and legal framework (I)

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