This is the first issue of the New Year and we wish all our readers a belated happy and healthy 2017! BJCP will announce many exciting innovations this year. One of them will be an experiment with video summaries of selected papers. The first 5 will be offered at no extra cost so we await proposals from authors who would like their paper disseminated not only as a pdf file but also as a video summary, which can be shared freely. Approach the editorial office if you have something that may be suitable.
Composite endpoints and the distortion of risk–benefit analysis
John B. Warren
DOI:10.1111/bcp.13166
Many trials lack power to detect effects of an intervention on a single endpoint and because of this, combined endpoints have been invented. These generally combine related events. For instance, a medicine preventing death from cardiovascular cause or myocardial infarction or heart failure may be effective on these endpoints taken together but not on each one separately. John Warren points out an interesting and perhaps disquieting unbalance in his editorial. Combined endpoints are used for desired effects but rarely for adverse effects, hence the power for detecting good things may be better than for detecting bad things.
Poor reporting and documentation in drug‐associated Stevens‐Johnson Syndrome and Toxic Epidermal Necrolysis – Lessons for medication safety
Caitlin Goldblatt, Sharmila Khumra, Jane Booth, Karen Urbancic, M. Lindsay Grayson and Jason A. Trubiano
DOI:10.1111/bcp.13103
Bad things about medicines are only known because they are reported. Toxic epidermal necrolysis and Stevens‐Johnson syndrome can be caused by many medicines but Caite Goldblatt and colleagues remind us that there may be serious underreporting.
The value of patient reporting to the pharmacovigilance system: a systematic review
Pedro Inácio, Afonso Cavaco and Marja Airaksinen
DOI:10.1111/bcp.13098
If doctors do not report adverse reactions, there is luckily the person at the receiving end of all this, Mr or Mrs Patient. Pedro Inacio and colleagues review the literature about patient reporting into the pharmacovigilance system. Undoubtedly useful and to be recommended even though we estimate that this will inevitably lead to over reporting, but that is likely to be better than under reporting.
Understanding and applying pharmacometric modelling and simulation in clinical practice and research
Joseph F. Standing
DOI:10.1111/bcp.13119
Joe Standing, a pediatric infectious diseases expert, gave a teaching session at last year's Pharmacology meeting on modelling and simulation. His summary of that session turned out to be everything you always wanted to know about this subject, but were afraid to ask. If you are into PK/PD papers with more equations than words skip this review…
Pharmacokinetics and pharmacodynamics of PF‐05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects
William S. Denney, Gabriele E. Sonnenberg, Santos Carvajal‐Gonzalez, Theresa Tuthill and V. Margaret Jackson
DOI:10.1111/bcp.13127
When you are reading this and suddenly feel you want something to eat, this is most likely due to gastric secretion of ghrelin, an important hunger inducing hormone. William Denney and colleagues report on an inverse agonist of the ghrelin receptor. In a first in human study they show inhibition of exogenously administered ghrelin acutely but also tolerance to this effect after longer administration, and effects on heart rate and sedation. We may get closer to finding out what this fascinating hormone does and perhaps also to the mechanism of postprandial sleepiness.
This paper also highlights a development we do not like. The authors all have their address in the USA and the study is performed in Belgium. We have clear rules that the primary investigator in a study like this should be an author. In this case this must be impossible and the investigators only received acknowledgement. We let it go this time because both the research unit and the authors were from the same pharmaceutical company, Pfizer, but remind our potential authors that we insist that the clinical investigator be an author. Our policy was explained in the editorial Cohen AF, Ritter JM. Industrialized research in the BJCP: A neo‐Luddite view. Br J Clin Pharmacol 2012; 74: 903–906. DOI: 10.1111/bcp.12000.
Translating QT interval prolongation from conscious dogs to humans
Vincent F. S. Dubois, Giovanni Smania, Huixin Yu, Ramona Graf, Anne S. Y. Chain, Meindert Danhof, Oscar Della Pasqua, on behalf of the Cardiovascular Safety Project Team and TI Pharma PKPD Platform
DOI:10.1111/bcp.13123
The so called thorough QT study became fashionable after a number of well publicised withdrawals of drugs because of torsades‐des‐pointes ventricular tachycardia caused by QT prolongation. These studies in humans were extremely costly and yielded relatively little in the sense of increased patient safety. Vincent Dubois and co‐investigators elegantly demonstrate that by using PK/PD modelling the dog is an excellent predictor of QT prolongation in humans.
An S‐warfarin and AZD1981 interaction: in vitro and clinical pilot data suggest the N‐deacetylated amino acid metabolite as the primary perpetrator
Ken Grime, Rikard Pehrson, Pär Nordell, Michael Gillen, Wolfgang Kühn, Timothy Mant, Marie Brännström, Petter Svanberg, Barry Jones and Clive Brealey
DOI:10.1111/bcp.13102
Finally for an elegant approach to study drug interactions with metabolites on warfarin look no further than this paper, which was, entirely as it should, written by a joint team from a pharmaceutical company and a research organisation based in a teaching hospital with all significant participants named as authors.
Prescribing Points
A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients
Evelien J. M. Kuip, Maarten L. Zandvliet, Stijn L. W. Koolen, Ron H. J. Mathijssen and Carin C. D. van der Rijt
DOI:10.1111/bcp.13129
Kuip et al. provide an excellent overview of pharmacokinetic factors which may impact on fentanyl use, particularly in cancer patients. This is a very helpful review for those of us looking after these often complex patients.
Eosinophilic drug reactions detected by a prospective pharmacovigilance programme in a tertiary hospital
Elena Ramírez, Nicolás Medrano‐Casique, Hoi Y. Tong, Teresa Bellón, Rosario Cabañas, Ana Fiandor, Jessica González‐Ramos, Pedro Herranz, Elena Trigo, Mario Muñoz, Alberto M. Borobia, Antonio J. Carcas and Jesús Frías
DOI:10.1111/bcp.13096
Ramirez et al. report on the features of eosinophilic drug reactions. These potentially serious reactions are found in a wide range of commonly prescribed drugs, and this paper provides a useful reminder for prescribers.
Managing drug–drug interactions with new direct‐acting antiviral agents in chronic hepatitis C
Sarah Talavera Pons, Anne Boyer, Geraldine Lamblin, Philip Chennell, François‐Thibault Châtenet, Carine Nicolas, Valérie Sautou and Armand Abergel
DOI:10.1111/bcp.13095
In a slightly more specialist area, Talavera Pons et al. describe interactions with the newer anti‐virals used to combat hepatitis C. For those using these drugs, and for prescribers who might interact with these patients, this is a helpful review of the evidence.