Ultimately, the fate of a molecule is in the hands of the FDA, which may seem like a monolithic bureaucracy but is an organization just like any other, composed of thousands of physicians, nurses, pharmacists, scientists, and, yes, bureaucrats. Each decision to approve or not approve an application is made by humans who follow guidelines and precedents, along with other definable and undefinable factors, while applying their own judgment.
From the point of view of those who are eagerly awaiting their drug's approval, it helps to understand how regulators think, what they care about, what they worry about, what are deal-breakers, and how they balance benefits and risks. Of course, these are basic questions the Regulatory Affairs department is always mulling over, but other contributors, including medical writers, may also find this knowledge useful in their work.
So where do we find clues to regulators' thinking? Besides the codified regulations and official guidances to industry, FDA posts on its website the reviews of each new drug that has been approved. With a little digging, you can access the opinions of the medical, pharmacological, and statistical reviewers. In a document labeled "summary review," the division director outlines his or her final decision with detailed rationale. All these reviews are available in the searchable FDA drug database.
Some of these reviews are fairly straightforward, but occasionally they reveal internal debates and some reviewers' bottom line. An interesting example is pimavanserin, an antipsychotic approved in 2016 for the treatment of psychotic symptoms associated with Parkinson's disease. In the summary review, we see that the medical reviewer recommended not to approve this drug because its safety concerns outweighed the "minimally clinically significant" efficacy. Nevertheless, the division director overruled the medical reviewer and approved this drug, citing a placebo-subtracted 13% of patients with no symptoms after treatment as one of the reasons for his decision. Another company developing a similar treatment can gain quite a bit of insight from this short document.
While different reviewers and divisions may have their own opinions and quirks, FDA tries to maintain a level internal consistency in the review process. In addition, the review staff and division management tend to be fairly stable over time. Thus, these reviews, at least for recent approvals, can be very informative when you are putting together an NDA, BLA, or an SPA (special protocol assessment) request.