For clinical researchers, the note to file, or NTF, is the mosquito that you can hear under the covers or the flat tire on the way to the interview. When left unchecked, the NTFs multiply to fill the trial master file, or TMF. When used to reduce confusion, NTFs reliably perpetuate it. When used to prevent inspection findings, NTFs often provoke them. So why do NTFs persist in clinical research when they consistently cause us so much pain?