ABSTRACT
Pharmaceutical companies are under increasing scrutiny because of their strategy for gaining market access and reimbursement authorisation for novel drugs. The tool most often used is that of a randomised controlled trial (RCT) in a highly selected population that has a high chance of responding on the treatment but a low chance of developing side effects. This population differs to a large extent from real-life patients, who have diverging characteristics that can influence effectiveness and safety; these include co-morbidity, age and disease severity. The ultimate consequence is that evidence resulting from RCTs is not immediately transferable to clinical practice. This paper illustrates examples of drugs developed for rheumatoid arthritis and hepatitis C. We discuss research designs that can complement findings from RCTs, such as pragmatic trials, enriched trials, adaptive pathways, early access programs and patient registries. The aim is to stimulate debate among different stakeholders so that they answer the right question at the right time using a suitable research methodology.
Subject(s)
Clinical Trials as Topic , Drug Industry/organization & administration , Prescription Drugs , Cost-Benefit Analysis , HumansABSTRACT
BACKGROUND: A new era for the treatment of chronic hepatitis C is about to transpire. With the introduction of the first-generation protease inhibitors the efficacy of hepatitis C treatment improved significantly. Since then, the therapeutic agenda has moved further forward with the recent approval of sofosbuvir and the expected approval of agents such as simeprevir and daclatasvir. This paper, developed parallel to the approval of sofosbuvir, is to serve as a guidance for the therapeutic management of chronic hepatitis C. METHODS: We performed a formal search through PubMed, Web of Science and ClinicalTrials.gov to identify all clinical trials that have been conducted with EMA-approved new agents in hepatitis C; for this version (April 2014) we focused on sofosbuvir. For each disease category, the evidence was reviewed and recommendations are based on GRADE. RESULTS: We identified 11 clinical trials with sofosbuvir and for each disease category recommendations for treatment are made. Not all disease categories were studied extensively and therefore in some cases we were unable to provide recommendations. CONCLUSION: The recent approval of sofosbuvir will most likely change the therapeutic landscape of chronic hepatitis C. The use of sofosbuvir-containing regimens can shorten the duration of therapy, increase efficacy and result in less side effects, compared with standard of care. The efficacy relative to standard of care needs to be weighed against the increased costs of sofosbuvir. With future approval of the other direct-acting antivirals, the outcome of hepatitis C treatment will likely improve further and this guidance will be updated.
