El equívoco terapéutico en los ensayos clínicos: combatirlo y convivir con él / Therapeutic misconception in clinical trials: fighting against it and living with it

Un ensayo clínico busca obtener datos para el beneficio de futuros pacientes y no necesariamente para los que participan en él. Sin embargo, hay pacientes que creen que obtendrán un beneficio terapéutico directo por participar en un ensayo clínico: es el denominado «equívoco terapéutico». En este artículo se describe la naturaleza y la extensión del equívoco terapéutico, que también pueden presentar los investigadores. Su presencia es especialmente relevante en ensayos con grupo placebo y en los de fase 1 de oncología. Para intentar limitar su aparición hay que asegurar que las hojas de información para los participantes estén bien redactadas, y que los investigadores establezcan una conversación efectiva y transparente en el proceso de obtención del consentimiento informado, de forma que el paciente conozca todos los matices de su participación en la investigación y valore lo que esto significa (AU)

A clinical trial seeks information for the benefit of future patients and not necessarily for those who participate in the study. However, there are patients who believe that they will receive a direct therapeutic benefit by participating in a clinical trial, the so-called «therapeutic misconception». In this article, we describe the nature and extent of therapeutic misconception, which researchers can also experience. Its presence is especially important in phase 1 oncology trials and those with placebo group. To limit its occurrence, investigators have to ensure that participant information sheet are well written and to establish an effective and transparent discussion during the process of obtaining informed consent so that patients understand all aspects of their participation in the research and appreciate what this participation entails (AU)

Therapeutic misconception in clinical trials: fighting against it and living with it. / El equívoco terapéutico en los ensayos clínicos: combatirlo y convivir con él.

A clinical trial seeks information for the benefit of future patients and not necessarily for those who participate in the study. However, there are patients who believe that they will receive a direct therapeutic benefit by participating in a clinical trial, the so-called «therapeutic misconception¼. In this article, we describe the nature and extent of therapeutic misconception, which researchers can also experience. Its presence is especially important in phase 1 oncology trials and those with placebo group. To limit its occurrence, investigators have to ensure that participant information sheet are well written and to establish an effective and transparent discussion during the process of obtaining informed consent so that patients understand all aspects of their participation in the research and appreciate what this participation entails.

Prediction of pneumococcal conjugate vaccine effectiveness against invasive pneumococcal disease using opsonophagocytic activity and antibody concentrations determined by enzyme-linked immunosorbent assay with 22F adsorption.

We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 µg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 µg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines.

Immunogenicity and safety of AS03-adjuvanted H1N1 pandemic vaccines in children and adolescents.

Vaccines with acceptable efficacy profile against the H1N1 A/California/7/2009 virus are needed for use in children. The two studies presented here evaluated the immunogenicity and the reactogenicity/safety of A/H1N1/2009 vaccines containing either 3.75 µg haemagglutinin antigen (HA) and AS03(A)-adjuvant (3.75 µg HA/AS03(A) study) (N=210 [53, 57 and 100 in the 3-5, 6-9 and 10-17 years age strata, respectively]) or 1.9 µg HA and AS03(B)-adjuvant (1.9 µg HA/AS03(B) study) (N=244 [61, 65 and 118 in the 3-5, 6-9 and 10-17 years age strata, respectively]), given as two-dose series. Although the haemagglutination inhibition antibody titres were higher in the 3.75 µg HA/AS03(A) study, both vaccine dosages were highly immunogenic and exceeded regulatory acceptance criteria after the first and the second doses. Seroprotection rates reached 100% and seroconversion rates ranged from 98.2% to 99.1% after each dose of both vaccine dosages. Geometric mean titres increased from 456.5 to 1538.5 and from 297.9 to 1106.7 between the first and the second doses in the 3.75 µg HA/AS03(A) study and the 1.9 µg HA/AS03(B) study, respectively. Despite an observed slight increase of the reactogenicity following the second dose in the 3.75 µg HA/AS03(A) study, the vaccines safety profiles were considered clinically acceptable. In conclusion, both dosages of the AS03-adjuvanted A/H1N1/2009 pandemic influenza vaccines were highly immunogenic and well-tolerated in children and adolescents.

Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study.

BACKGROUND: We aimed to assess the efficacy of the oral live attenuated human rotavirus vaccine Rotarix (RIX4414) for prevention of rotavirus gastroenteritis in European infants during their first 2 years of life. METHODS: 3994 study participants were enrolled from six countries and were randomly assigned two oral doses of either RIX4414 (n=2646) or placebo (n=1348), which were coadministered with the first two doses of specific childhood vaccinations. Follow-up for gastroenteritis episodes was undertaken from 2 weeks post-dose two through the two consecutive rotavirus seasons following vaccinations (combined efficacy follow-up period; mean duration 17 months [SD 1.6]). Our primary endpoint was vaccine efficacy against rotavirus gastroenteritis of any severity during the first efficacy follow-up period (2 weeks post-dose two to the end of the first rotavirus season). Stool specimens obtained during gastroenteritis episodes were tested for rotavirus by ELISA and typed by RT-PCR. Episodes scoring 11 or greater on the 20-point Vesikari scale were classified as severe. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140686 (eTrack102247). FINDINGS: 120 infants were excluded from the according-to-protocol analysis. During the first efficacy follow-up period (mean duration 5.7 months [SD 1.2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87.1% (95% CI 79.6-92.1; p<0.0001). For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90.4% (85.1-94.1; p<0.0001), for admission owing to rotavirus gastroenteritis 96.0% (83.8-99.5; p<0.0001), and for rotavirus-related medical attention 83.8% (76.8-88.9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown. INTERPRETATION: In a European setting, two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis, with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons.

[Early detection of congenital hypothyroidism. Study of 31,609 determinations]. / Detección precoz de hipotiroidismo congénito. Estudio sobre 31.609 determinaciones.

As a result of congenital hypothyroidism (CH) early detection program carried out in our clinic during the period 1978-1981, 31.609 capillary blood samples (35,7% from newborn infants) were taken on filter paper cards. An evaluation of TSH following the specific radioimmunoanalysis technique was made in all the samples, and an evaluation of T4 whenever TSH values were higher than 25 microU/ml serum. Thirteen cases of CH were detected: nine with permanent H and four with transient H. Two cases of hyperthyrotropinemia were also detected. Frequency of permanent CH in our population is of 1/3.512. Corresponding biochemical data and detailed clinical characteristics detected, including the cost of the procedure are shown. Authors emphasize on possibility of preventing brain damage and subsequent subnormality through early detection and treatment of congenital hypothyroidism, together with a suitable cost-benefit ratio, makes necessary to carry out a nationwide campaign in accordance with those centers already established.

[Pathogenic factors and therapeutic criteria in 82 newborn infants with necrotizing enterocolitis]. / Factores patogénicos y criterios terapéuticos en 82 recién nacidos con enterocolitis necrotizante.

Sixty newborn infants with necrotizing enterocolitis (NEC) were retrospectively studied in 1979. The incidence was 0,49/1.000 living newborns: 81% were under 2,500 g and 30% under 1.500 g. We found a very low incidence of the so-called pathogenic factors. Feeding started in this group on the 24 h of life, with adapted formulas; 28% underwent surgery with a postoperative mortality of 62% and an overall mortality of 28%. Ten out of the 17 deceased were under 1.500 g. From 1979 with a similar medical treatment we introduced a prospective study consisting of a protocol of 10 different parameters including clinical, radiological and analytical values, the aim being a more objective way of indicating when to operate the patient. Special meticulous care of the nutrition of the low-weight babies was taken; 22 patients were treated til 1982, only 4,5% were under 1.500 g. The initial feeding time in all high risk babies under 1.250 g being 7 days with gastric gavage and elementary diets. All the infants with more than 60% values in the protocol underwent surgery (38%). The postoperative mortality was 37% with an overall mortality of 19%. A look back to our series suggests a clear usefulness of the protocol and the suspicion that the delay on feeding with intragastric continuous perfusion in low weight babies reduces NEC.

[Treatment of patent ductus arteriosus in preterm infants]. / Tratamiento del "ductus" arterioso persistente en recién nacidos pretérmino.

A retrospective study is made on the results of the treatment of 38 preterm infants with symptomatic PDA; they represented an incidence of 4% of all the admissions to our Unit from June 1978 to March 1980. 30 of the 38 infants (79%) had PDA associated with RDS. Conservative medical treatment failed in 42% of the patients, requiring the administration of indomethacin for pharmacologic closure of their PDA. The different responses to the drug in each of the established groups are commented, being the group with a birth weight less than 1,500 g who presented the highest percentage of re-openings (62.5%) and of therapeutic failures (50%). An early closure of the PDA can contribute to decrease the morbidity and mortality of these infants, specially those with lower birth weight.