Table 1. Design element groups and annotation options for use with an AFLEX (automatic functional language recognition/EXtraction) interface for annotating portable document format files.

Design element	Element options	Comments
Comparison group	None	There is only one group in the study and this group received the intervention. This group may serve as its own control, i.e., the outcome is assessed prior to and following application of the intervention(s).
	Concurrent	The design has two or more comparison groups that occur at the same time.
	Historic	The design has at least one comparison group that completed the study before the other comparison group(s) entered the study.
Unit of concern	Group	The factors are applied at the level of the group, such as cage or other housing.
	Individual	The factors are applied at the level of the individual.
	Nested	There are two or more hierarchical levels of the factors (e.g., one factor applied to pregnant mother, and a second factor applied to the pups).
Arrangement of factors	Parallel	Two or more experimental groups are followed over time. Interaction between factors is not studied.
	Cross-over	At least two experimental groups are in the study, and the groups swap interventions.
	Complete factorial	At least two factors are studied and all possible combinations of these factors are present in the design. These factors are applied at the same level. (all factors applied at single level).
	Incomplete factorial	At least two factors are studied but not all possible combinations of these factors are present in the design. These factors are applied at the same level. (all factors applied at single level).
	Split-plot	Factors are investigated at two or more hierarchical levels in the study, i.e., one or more factors are nested within another factor (e.g., whole mouse, two or more tissues within the mouse).
Allocation	Random	Refers to the use of a random allocation methods
	Systematic	Refers to the use of alternation methods.
	Minimization	Minimization includes matching on known confounders based on previously enrolled animals.
	Haphazard	A method that is none of the above, such as allocating the next intervention to the next mouse caught. Rarely is the word "haphazard" used; however, a described method might appear haphazard.
Concealment	Blinded intervention allocation	The investigators indicated whether the allocation sequence was concealed prior to enrolment.
	Blinded outcome assessment	The investigators indicated whether the outcome assessor(s) was/were blinded to the intervention groups.
Independence	Pseudo-replication	Pseudo-replication is considered multiple measures of an outcome designed to capture random experimental noise, i.e., multiple pups within a litter when the dam had been allocated to treatment or multiple tissue sections within an animal.
	Repeated measures	Repeated measures refers to multiple measurements of an outcome when a factor is varied. The multiple outcome measurements are spread across a factor of potential interest, such as time or decibels.
Investigator-identified study design	Investigator-Identified Study Design	The study design, as identified by the study investigator(s) in the Title, Abstract, Keywords, Objectives, and/or Methods sections of the article.
Nature of the factors allocated	All could be randomized Some could be randomized None could be randomized	The investigators examined only factors that could be randomized (e.g., drugs, exercise treatments, diets, etc.) The investigators examined a mixture of factors that could be randomized and factors that could not be randomized. The investigators examined only factors that could not be randomized (e.g., sex, genotype, age, and tissue type (when more than 1 type of tissue was sampled per experimental unit)).