While a 50% increase is...high...to my knowledge, research costs still inflate as other techs are researched. This may be a side effect of military techs having an additional modifier in 2.0 that makes them cost more (and may also cause them to increase inflation faster, though I personally have not tested that aspect of it).
When you say third or fourth missile defense, what tech specifically do you mean? I'm unaware if you're speaking in absolute terms, i.e. three techs down the missile line (ECM?), or relative, for instance, three or four tiers down the missile line-not counting Chaff, this could put you as far as Droid Sentries. That's a fairly large difference, so would you care to elaborate?
Additionally, could you right click and verify that the cost has indeed increased by 50%? Do you have any research treaties with minors or majors? This influences your research "rate" as well, and if they decide to turn down their research output for a few turns, it can hurt-especially if you're not doing that much researching yourself.
One other thing to check that may be obvious (as it would have other, more far-reaching side effects) is to ensure that you have not somehow been hit by the plague, as this reduces all abilities to zero, and if you have/had any research bonus, it will be nullified for the duration.