A senior PSNI officer has told the Policing Board that while the Omagh bomb investigation remains open, progress is unlikely.
Twenty-nine people, including a woman pregnant with twins, were killed in the Real IRA attack in 1998.
On Tuesday, the prosecution of 45-year-old County Armagh man Seamus Daly for the bombing collapsed.
Deputy Chief Constable Drew Harris said there were currently no new lines of inquiry in the investigation.
"Police profoundly regret that we have, to date, been unable to secure a conviction for the Omagh bombing and that individuals and families in Omagh and beyond who deserve justice have yet to secure it," he said.
"As we have said before, what is needed is for those people who know who did this to come forward and tell us what they know.
"Police need people to make statements and give evidence. Without this assistance, any prosecution is highly unlikely but police will not give up."
The Public Prosecution Service decided there was no reasonable prospect of conviction in the Daly case. He was released from Maghaberry Prison on Wednesday.
The prosecution case was withdrawn after a key witness gave inconsistent evidence and contradicted his previous testimony.
The Omagh bomb was the biggest single atrocity in the history of the Troubles in Northern Ireland.
It happened just four months after the Good Friday Agreement was signed.