Digital aripiprazole or digital evergreening? A systematic review of the evidence and its dissemination in the scientific literature and in the media
Evidence synthesis
Lisa Cosgrove1,
Ioana Alina Cristea2,3,
Allen F Shaughnessy4,
Barbara Mintzes5,
Florian Naudet6
1 Counseling and School Psychology, University of Massachusetts Boston, Boston, Massachusetts, USA
2 Clinical Psychology and Psychotherapy, Babes-Bolyai University, Cluj-Napoca, Romania
3 METRICS (Meta-research Innovation Center at Stanford), Stanford University, California, USA
4 Department of Family Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA
5 School of Pharmacy, Faculty of Medicine and Health, and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
6 Univ Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), Rennes, France
Correspondence to Dr Lisa Cosgrove, Counseling and School Psychology, University of Massachusetts Boston, Boston, MA 02125, USA; Lisa.Cosgrove{at}umb.edu
Background In November 2017, the Food and Drug Administration (FDA) approved a version of a second-generation antipsychotic, aripiprazole, embedded with a sensor (Abilify MyCite).
Objective To systematically review the evidence supporting the FDA's approval of digital aripiprazole and how that evidence was disseminated in the scientific literature and news reports.
Study selection Prospective, double-blind, randomised controlled trials (RCTs), non-randomised and non-comparative studies were included if they focused on the use of digital aripiprazole. All scientific publications citing the trials were included if written in English. For the news reports, all languages were included if an English translation was available, and all records that were published after FDA approval were included.
Findings In the primary evidence search, no RCT comparing digital aripiprazole with a non-digital formulation, other active comparators or placebo was found. Only three non-comparative uncontrolled cohorts were found. No study provided data on remission, quality of life or any efficacy outcome. Fourteen scientific papers were identified that cited the trials and 70 news stories met the inclusion criteria. Almost 80% (11/14) of the scientific papers and three-fourths (52/70) of the news stories conveyed an unsupported impression of benefit.
Conclusions Regulatory approval for this first-ever digital drug was based on weak evidence, and there was no evidence of better adherence with the digital version of aripiprazole compared with the non-digital version. The possibilities afforded by this technology make room for a new type of evergreening (ie, patenting of older drugs with a sensor as a 'new invention'). Both the scientific literature and news reports conveyed an unsupported impression of benefit.
Trial registration number CRD42018089515.
http://dx.doi.org/10.1136/bmjebm-2019-111204
Contributors LC conceived of the study. LC and FN developed the design. LC, FN, IAC, BM and AFS contributed to data analysis and interpretation and review of the results. All authors discussed the results and contributed to writing the manuscript. LC took the lead in writing the initial draft, and FN wrote the draft of the primary evidence search and results. All authors contributed to writing subsequent revisions of the manuscript.
Data sharing statement Data are shared on the Open Science Framework (https://osf.io/auc9e/).
Correction notice This article has been corrected since it was published Online First. Second affiliation for Ioana Alina Cristea has been corrected.
Patient consent for publication Not required.
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Digital medicine systems: an evergreening strategy or an advance in medication management?
Alexander C Egilman Joseph S Ross
BMJ Evidence-Based Medicine 2019; 24 203-204 Published Online First: 21 Nov 2019. doi: 10.1136/bmjebm-2019-111265