Evidence based methodology for evaluation of clinical efficacy and safety of drug therapy - A case for digestive diseases

Abstract

Decisions in health-care have become extremely complex and difficult since they involve a complex web of input and uncertainties. It is necessary to draw information from many sources such as primary data, preference of patients, clinical experiences, personal opinions, medical and legal regulations and, last but not least, scientific evidence. Nevertheless, the weight of the scientific evidence is critical, and indeed the evidence-based approach is now a “must”. However, the number of scientific publications exploded over the last 50 years, making scientific updating very difficult. Scientific publications taken individually or in small groups selected randomly, can often present confusing and, in some cases, even contradictory results. To establish efficacy, safety as well as utility of a health-intervention it has become increasingly common performing systematic reviews and meta-analyses. These tools allow to get an updated and a comprehensive assessment (even if not the definite one) of the health-intervention evaluated. In this dissertation, we present the results of an evidence-based approach concerning three gastroenterological issues. It was assessed the effectiveness and the safety of rifaximin to treat the small intestine bacterial overgrowth (SIBO), which is a heterogeneous syndrome characterized by an increased number and/or abnormal type of bacteria in the small bowel, and well-recognized as cause of maldigestion and malabsorption. Rifaximin is a poorly absorbed antibiotic with a broad spectrum of antibacterial activity, covering Gram-positive and Gram-negative microorganism, both aerobes and anaerobes, fulfilling the characteristics set by DuPont and Ericsson for the ideal antimicrobial that should be used for the treatment of gastrointestinal infections. As a consequence, over the past decades, rifaximin has been largely used to treat SIBO even if there was a lack of a critical summary of evidence. Systematic reviews and meta-analyses represent the basis do draw evidence-based guidelines on drug use in given clinical conditions. By reviewing and distilling a large body of literature, we developed a Position Paper addressing benefits and harms proton pump inhibitor (PPI) therapy in the treatment of acid-related diseases. Studies in primary care and emergency settings have indeed suggested that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Finally, since National Health Systems are currently collapsing, pharmacoeconomic analysis represents an integral part of the decision process. However, the evaluation of economic impact of a given treatment is often biased and influenced by Companies’ pressure. In this connection, we showed that the conclusions of an article concerning tapentadol ER - in comparison with oxycodone/naloxone CR - were misleading. Indeed, with a robust methodological and meta-analytic approach we were able to show that the comparisons made by the Authors were incorrect and actually reached an opposed conclusion.