Table 2.

Internal validity threats in Phase III chemotherapy-induced peripheral neuropathy prevention and management trials

Drug	Year	Author	Sample heterogeneity	Malapropos intervention mechanism of action	Malapropos intervention dose	Malapropos timing of outcome measurement	Confounding variables	Lack of valid and reliable measurement	Lack of statistical validity	Study design
Prevention (n=17)
Acetyl-L-carnitine	2013	Hershman						x	x
Alpha lipoic acid	2014	Guo					x		x
Amifostine	1996	Kemp					x	x	x
Amifostine	2003	Lorusso					x	x	x
Calcium/magnesium	2008	Grothey				x	x	x	x
Calcium/magnesium	2010	Ishibashi					x	x	x
Calcium/magnesium	2011	Grothey					x	x	x
Calcium/magnesium	2013	Gobran					x	x
Calcium/magnesium	2013	Loprinzi						x
Glutathione	1995	Cascinu					x	x
Glutathione	1997	Smyth					x	x
Glutathione	2002	Cascinu					x	x
Glutathione	2013	Leal				x		x	x
Goshajinkigan	2015	Oki					x	x	x
Venlafaxine	2015	Zimmerman					x	x	x
Vitamin E	2010	Pace					x		x
Vitamin E	2011	Kottschade						x	x
Management (n=7)
Duloxetine	2013	Smith
Gabapentin	2007	Rao	x		x		x	x	x
Lamotrigine	2008	Rao					x	x	x
Nortriptyline	2002	Hammack		x				x
Topical BAK	2011	Barton	x	x			x
Topical AK	2014	Gewandter	x	x		x
Venlafaxine	2012	Durand							x

BAK: Baclofen amitriptyline ketamine, AK: Amitriptyline ketamine