The changes were announced in a report by chief medical officer Professor Sir Liam Donaldson at the end of a review of organisational patient safety arrangements.
The report largely backed the findings of an internal NPSA review which called for patient safety expertise to be devolved to the regions.
The review was ordered after reports from the National Audit Office and the Commons public accounts committee criticised the agency for delays in delivering the system and failing to make an impact at trust level.
The Safety First report acknowledges that while the NRLS is receiving around 60,000 incident reports a month, 'it has been very difficult to establish a timely, complete and accurate picture of the major safety problems faced by the NHS'.
But it identifies a number of barriers to progress, including: poor data in incident reports; poor engagement by senior clinicians; and a failure by NHS organisations to review and act on analyses.
In response, it says a national forum will be established to bring together key agencies responsible for patient safety, to share best practice and co-ordinate action.
It says the reporting and learning system should be easier for staff to use, that there should be a national campaign to encourage them to engage on patient safety, and action teams to provide frontline support.
And it says patient safety should be 'deeply embedded' in NHS priorities, targets and goals and that families and patients should be involved in promoting safety and given support when things go wrong.
Action against Medical Accidents chief executive Peter Walsh welcomed the report and its emphasis on a 'no blame' culture.
'There is a new sense of urgency,' he said. 'There is a genuine statement of intent and practical measures to move things forward.'
NHS Confederation chief executive Dr Gill Morgan welcomed the report's recommendation to refocus the work of the NPSA in particular. 'It is only through learning from its mistakes that the NHS will be able to improve' she said.
NPSA chair Lord Patel said: 'We recognise that we need to change our focus, and are committed to doing so.'
NPSA joint chief executives Susan Williams and Sue Osborn have been on 'extended leave' since August.