Clinical trial designs of new medicinal products for treating schizophrenia: discussion of EMA's Guideline and a Better Long Term Trial Design

Background and Objectives: Schizophrenia is a severe chronic disease. Endpoint variables lack objectivity and the diagnostic criteria have evolved with time. In order to guide the development of new drugs, European Medicines Agency (EMA) issued a guideline on the clinical investigation of medicinal products for the treatment of schizophrenia. Methods: Authors reviewed and discussed the efficacy trial part of the Guideline. Results: The Guideline divides clinical efficacy trials into short-term trials and long-term trials. The short-term three-arm trial is recommended to replace the short-term two-arm active-controlled non-inferiority trial because the latter has sensitivity issues. The Guideline ultimately makes that three-arm trial a superiority trial. The Guideline discusses four types of long-term trial designs. The randomized withdrawal trial design has some disadvantages. Long-term two-arm active-controlled non-inferiority trial is not recommended due to the sensitivity issue. Extension of the short-term trial is only suitable for extension of the short-term two-arm active-controlled superiority trial. The Guideline suggests that a hybrid design of a randomized withdrawal trial incorporated into a long-term parallel trial might be optimal. However, such a design has some disadvantages and might be too complex to be carried out. Authors suggest instead a three-group long-term trial design, which could provide comparison between test drug and active comparator along with comparison between the test drug and placebo. This alternative could arguably be much easier to carry out compared with the hybrid design. Conclusions: The three-group long-term design merits further discussion and evaluation.

Hazardous drugs: new challenges, new opportunities

Occupational exposure to hazardous drugs can cause harmful effects on health professionals and several protective measures must be taken. Nevertheless, classification of hazardous drugs is not the same in all the published repertoires and the terminology is still confusing: hazardous drugs, biohazardous drugs or risky drugs are terms improperly described and can define very different drugs with a very different hazard profiles. In Spain, there is not an updated official list of hazardous drugs, and healthcare professionals must consider and follow other published lists. In our opinion, it is mandatory to do a consensus among these professionals, administration and labor union organizations in order to clarify some conflictive questions not only in healthcare settings but in investigational and academic scenarios too. These multidisciplinary groups should be involved also in teaching new and non-experienced personnel and in the knowledge reinforcement for the experienced ones.

Pre-exposure prophylaxis for the prevention of HIV infection: a new prevention paradigm?

Pre-exposure prophylaxis" (PrEP) has been recently developed as a prevention strategy which involves the administration of drugs to non-infected individuals who present high exposure or susceptibility to HIV. Although this use is not approved in our country, several guidelines recommend PrEP as a prevention option in adult MSM, heterosexual men and women, and users of parenteral drugs at risk of acquiring the infection. This article presents the characteristics that an ideal agent to be used as PrEP should meet, recent efficacy published data and barriers for the implementation of this new strategy. On the other hand, the role of hospital pharmacists will be discussed.