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One solution to reduce invalid clicks is to remove publishers who have zero content and 100% Advertisements. Also one more popular advertising format is to have the top fold of the page filled with ads with content at the bottom (which is not visible untill you scroll down). This should also be banned.
What works best is to provide content on your own site, more than what the user expects, so they stay on your site longer and then create links to funnel them into a purchase or lead. In order to do this you need an analytics program loaded with features. (Google Analytics works very well).
Tip: Add keywords that always appear on 'parked domains' to your negative keyword list. The content network takes into account your negative keywords. Some examples on the top of my head:
-buy this domain
-domain for sale
-domain may be for sale
-domain names for sale
There is a chance where group of people may form a ring and click on other's parked domains.
If you think about it it makes sense - if someone is going to the trouble of both typing in a relevant domain like widgets.com and then secondly clicking an ad for that kind of product, then they definitely are interested in buying.
But I guess there is a wide variation of domains, not all are so well targetted to running specific commercial ads.