> This casts doubt on the pre-registry studies.

I think you mean, 'This casts doubt on the non-registered studies'.

Yes, but as noted in the article some of that may be because of other factors that have changed in the meantime. I.e. if hospital treatment for heart disease has advanced and noticeably affects outcomes at that level, it could change the overall outcome of a study about heart disease.

I myself don't anticipate that accounting for much though.

Without intimate familiarity in the field it's really hard to figure out cause and effect in something so complicated.

It's been noted that it's become much harder to find new drugs. Conventional explanations are that we're pretty good at this by now, and all the low hanging fruit has been picked (there's also fields like antibiotics where few are trying for unrelated issues).

More rigor in studies could be a cause, and/or there may be fewer successes because its become that much harder, and more iffy attempts are being made.

Yes, that's a more eloquent way of saying exactly what I was trying to express, and what I interpreted the article as alluding to. Thanks!