The detectives have interviewed 442 people over the last couple of years and have identified 41 potential suspects, although no arrests have been made.
In the BBC Crimewatch program on Monday night, e-fits of men seen in and around Praia da Luz at the time will be published in a bid to identify the men and eliminate innocent sightings.
"Primarily what we sought to do from the beginning is try and draw everything back to zero,'' said the chief investigating officer, Detective Chief Inspector Andy Redwood, in a clip from the program released to the media.
"Try and take everything back to the beginning and re-analyse and reassess everything, accepting nothing.''
He said detectives were focused on the time between 8:30pm on May 3, 2007, when Kate and Gerry McCann left the apartment to dine at a nearby tapas restaurant with friends, to when Kate McCann found Madeleine was missing at 10pm.
"Our work to date has significantly changed the timeline and the accepted version of events that has been in the public domain to date,'' Redwood added.
The appeal will be shown in Germany and the Netherlands after Monday's British broadcast, in a bid to widen the search for new information.
Last week the McCanns said they were "greatly encouraged by new information coming to light'' and said they hoped the BBC appeal would take them closer to find Madeleine.
- AFP