Watch for visual splices, clicks/pops/skips in audio, and checking for the use of cheating techniques. Check nick token counts. At start of game, the token count must be 0, and life count 4 (except NG+). Each level should have a consistent token count and life count from then on. Between level transitions and upgrades, ensure the count never changes inexplicably. Make sure that they get every upgrade (except NG+) and that the upgrades seen in gameplay match those that were gotten thru menus.
Brief pauses and hangups happen. These occur on console, and are normal.
Re-time the run. Do not use their split timer unless you have made sure it is accurate. Use visual cues: the screen's initial cut to black, and the last pixel of green in calamitous' health bar disappearing for full game.