Article ; Online: The 2022 Ferno Award Address: CrEATE, an Efficient Crossover Evaluation of Addiction Treatment Efficacy.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
2022 Volume 25, Issue 1, Page(s) 77–85
Abstract: Dozens of drugs have been evaluated in recent decades for initial evidence of efficacy to aid smoking cessation (i.e. "early Phase 2" testing, according to U.S. FDA terminology), with the vast majority failing to show efficacy. Even small randomized ... ...
| Abstract | Dozens of drugs have been evaluated in recent decades for initial evidence of efficacy to aid smoking cessation (i.e. "early Phase 2" testing, according to U.S. FDA terminology), with the vast majority failing to show efficacy. Even small randomized clinical trials (RCTs), the most common early Phase 2 tests, are costly undertakings, made more unappealing by their high likelihood of failure. At the same time, another early Phase 2 approach, acute tests of drug effects on surrogate endpoints such as withdrawal or craving severity, are more practical but have little predictive clinical validity. Described here is an innovative procedure that optimally combines the validity of clinical trials with the practical advantages of surrogate endpoint studies to more efficiently determine whether or not a novel drug warrants continued clinical development. This CrEATE procedure, or Crossover Evaluation of Addiction Treatment Efficacy, does so by assessing short-term quit success in smokers highly motivated to quit when briefly treated with active drug versus placebo in a crossover design, so that quit efficacy from both conditions is compared within participants. The program to develop and evaluate CrEATE demonstrates its sensitivity to efficacy from all three FDA-approved first-line cessation medications (NRT, varenicline, bupropion), tested here as model drugs, as well as specificity in identifying lack of efficacy with a drug known to be ineffective for cessation (modafinil). CrEATE has subsequently been used to evaluate a few novel interventions, concluding they lack efficacy in increasing quit success. Future directions for the potential utility of CrEATE are provided. Implications: The ability of CrEATE to reach a Go/No Go decision more quickly and with far less cost lowers the risk of failure, meaning widespread use of the procedure should encourage the evaluation of more novel candidate drugs. With its greater efficiency, failed tests, unfortunately the most likely outcome in early Phase 2 studies, will cause less waste of resources. At the same time, CrEATE tests that indicate a novel treatment has efficacy will justify the substantial time and expense of moving forward to evaluate the drug in late Phase 2 RCTs. |
|---|---|
| MeSH term(s) | Humans ; Nicotinic Agonists/therapeutic use ; Cross-Over Studies ; Benzazepines/therapeutic use ; Smoking/drug therapy ; Varenicline/therapeutic use ; Bupropion/therapeutic use ; Treatment Outcome |
| Chemical Substances | Nicotinic Agonists ; Benzazepines ; Varenicline (W6HS99O8ZO) ; Bupropion (01ZG3TPX31) |
| Language | English |
| Publishing date | 2022-06-04 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 1452315-2 |
| ISSN | 1469-994X ; 1462-2203 |
| ISSN (online) | 1469-994X |
| ISSN | 1462-2203 |
| DOI | 10.1093/ntr/ntac139 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 5789: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.