Table 1.

Main differences between randomized clinical trials (RCTs) and animal intervention studies

RCT	Animal intervention study
Objective: demonstrating clinical efficacy	Objective: understanding disease mechanisms, suggesting intervention strategies(guiding clinical trials), examining potential efficacy, safety and toxicity of interventions
Disease naturally present	Disease often induced (with unclear/insufficient similarity to the human condition)
Timing of applying the intervention in relation to the disease onset is often heterogeneous	Intervention is often applied at a known time point in relation to the induced disease state
Often a heterogeneous group of patients (for example, lifestyle and co-morbidities)	Often a considerably homogeneous study population (e.g., comparable/controlled housing conditions and animal characteristics such as genetic backgrounds, gender, and presence of co-morbidities)
Sample size relatively large (compared to animal studies)**	Sample size relatively small (compared to RCTs) and sample size calculations often not reported
In general, relatively high internal validity because of randomization and blinding (compared to animal studies)**	In general, low internal validity (compared to RCTs)
	E.g., not yet standard practice to:
	-Randomize allocation of the animal to the intervention and control groups
	-Blind personnel and outcome assessors
Patients can be blinded for treatment in many situations.	Animals cannot and need not be blinded for treatment.
Relatively high external validity (extrapolation within one species)	Relatively low external validity (extrapolation between different species)
Relatively large teams involved	Relatively small teams involved
Intervention staffs are often different from outcome assessment staff.	One researcher is often responsible for treatment allocation and administration, outcome assessment and data analysis.
In general, no post-mortem data	In general, post-mortem material available
	Animals are often sacrificed at the end of the experiment.
Outcomes are often patient-relevant outcomes (compared to animal studies)	Outcomes are often surrogate outcomes, and still difficult to translate to the clinical setting even if similar to clinical outcomes
Clear guidelines for reporting and methodological quality [25]	Evolving guidelines for reporting and methodological quality [2,23,24]

**Additional file 1 provides some supportive information for this statement.

The differences described in this Table indicate general tendencies and may, therefore, not apply to all RCTs and animal intervention studies.