Table 2. Effects of different standards of prevention on key parameters.

	Participant and community welfare	Scientific viability	Efficiency	Usefulness
Standard of prevention:
Enhanced prevention package: adding new biomedical products or procedures that are not locally available	Positive: Potential direct benefits to participants; benefits to long-term stakeholder relationships amongst community, host country, researchers, research sponsors;	Positive: no bias created if same methods offered to both/all arms;	Positive: possibility of greater attractiveness of trial and faster enrollment	Positive: policy makers may be interested in combination approach; as new methods become more widely available, trial may predict “real world” outcomes; may contribute to driving towards improved standards of care (short or long term)
	Negative: increase inequity within study community; potential negative effects on adherence; potential diversion of products	Negative: potential for unintended adverse biological interactions with untested combinations of interventions;possible challenges of interpretation of effectiveness of individual prevention modalities	Negative: Possibility of increased trial costs/time due to lower HIV incidence across all arms of trial	Negative: Regulators may only issue approval for products when used in combination; possible decreased policy relevance (policy makers may not want to implement entire package); policy makers may be interested in results of single method used alone;
Active control arm: using biomedical prevention method as active control	Positive: Potential for:direct benefits to participants;	Positive:	Positive:	Positive: hold new products to high standard; (match or beat control); see results of two methods in same trial to base future policy decision-making on comparable data from same population;
	Negative: increase inequity within study community; potential diversion of products; more difficult to justify randomization to experimental arm with a known effective control arm	Negative: Possible false positive results in non-inferiority designs; cannot detect efficacy of products less efficacious than control arm	Negative: increase in sample size to detect difference between arms and establish non-inferiority or superiority; increased trial size, duration and cost;	Negative: Regulators may not accept trial design for marketing approval; policy decisions based on false positive result could waste health funds, increase risks; products with lower efficacy than control, but still with public health value (for example more feasible or acceptable), may not be considered for implementation