In a new interview BioWare's Mike Gamble revealed that Commander Shepherd can 'lose' in Mass Effect 3. Without going into details he explains that,

"In Mass Effect 3, the theme is literally galactic extinction, so the choices that you make can have that much larger consequences, and because of that, you think a little bit harder before making them."

Confirming that it is the decisions the player makes that will effect your eventual out come he added,

"A lot of the satisfaction comes out of the choices that you made, so when a story concludes a certain way, the way it concluded was in part because of the choices you made."

A video of the interview can be seen here, [1]

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