Evaluación cualitativa y cuantitativa de los estudios posautorización de tipo observacional registrados en España

Abstract

Main Objective: To study the impact of the regulation regarding non-interventional post-authorization studies on their methodological and ethic quality in the investigated period. Secondary objectives: To estimate the concordance between the decisions of the competent authorities regarding the application for authorization of these studies. To estimate the concordance among the reasons of authorisation refusal by the competent authorities. Method: Non-interventional post-authorization studies registered in Spain from 25th April 2000 to 31st December 2011 were reviewed. Relevant information from the protocols was extracted, including: administrative, methodological and monitoring information. Study authorization or non-authorization decisions by the competent authorities were also gathered. Results of each regulatory period were compared with those of the previous one, and results of the overall regulatory period were compared with the period without regulation. The concordance between the decisions of the competent authorities was estimated for each autonomous community (Kappa test for two independent observers with two categories was calculated). Pooled concordance was estimated for the different aggregate regulatory periods (Kappa test for three or more independent observers with two categories was calculated). Multivariate logistic regression predictive models were built for autonomous communities who notified enough number of decisions, in order to evaluate the strength of the association between the protocol’s characteristics and the study authorization decision. Main results: Overall, the regulatory period (2002-2011) showed better results compared with the non regulated period (2000-2002). A higher proportion of studies had: international scope (35.24% vs. 4.28%, p<0,001), follow-up longer or equal to 12 months (46.,5% vs. 23.68%, p<0,001), request of the informed consent (85,64% vs. 19,5%), evaluation by an Ethics Committee (96.87% vs. 9.48%, p<0,001) or description of the data confidentiality procedure (84,64% vs. 41,28%, p<0,001). The registry rate (number of studies registered/100 days) was similar in both periods (38,85 vs. 40,06). The lowest registry rate (19.08) was observed in the 2002-2007 period, being the studies with prospective follow-up design sponsored by pharmaceutical industry those which exhibited the largest decrease as compared to the previous period. Authorization refusals by autonomous communities showed a decreasing trend (Andalucía -from 43.06% to 27.85%-, Aragón -from 81.52% to 29.03%-, Cataluña -from 44.83% to 14.55%- o Madrid -from 59.73% to 27.71%-). Low kappa values were observed in the decisions by the autonomous communities (0.16 in the 2002-2007 period, 0.15 in the 2007-2009 period and 0.25 in the 2009-2011 period). No common predictors for the study authorization or refusal were found in the analyzed autonomous communities. Conclusions: The Spanish regulation regarding non-interventional post-authorization studies showed a great impact. Ethical quality was improved and to a less extent methodological quality improved too. The research activity using observational studies didn’t decrease in the regulatory period compared with the period without regulation. This regulation is considered the first that has demonstrated to be effective in the minimization of the promotional use of the observational studies. The concordance between the decisions of the competent authorities was poor, and the evaluation criteria showed lack of homogeneity. Forthcoming regulations should be focused on the improvement of the identified issues.