Common Reasons for Delays in CTA Applications

Good Practices in Trial Design Stages

Applications to the MHRA for a Clinical Trial Authorisation (CTA) are the result of a long and intensive consultative process involving the sponsor, principle investigators, the trial administrator and other researchers involved in organising the clinical trial. It is therefore not uncommon for a CTA to be submitted late in the trial design stage, with little time to spare for unplanned contingencies, before a trial is scheduled to begin.

Although the MHRA receives over 1,200 CTA applications a year it has one of the fastest response times in the EU with regards to assessing valid CTA applications. However, it will not assess invalid CTA applications until all deficiencies are rectified. Furthermore, once an application is considered to be valid, delays can be incurred if the MHRA has to issue a ‘request for further information’ to clarify one of more aspects of the application. In a recent MHRA statistic, of all letters sent to request further information, 42% were to request basic information which should have been included in the initial application. In most cases, such delays are down to the quality of the CTA application and therefore avoidable by the research team. In an attempt to address the issue, the MHRA has published a list of (a) common causes of applications being considered invalid as well as (b) common grounds for request for further information.

Common causes for invalid CTA applications

In practice, the MHRA validates every CTA on receipt and only valid applications are further processed for assessment (note that the 30 day limit only starts from the date of receipt of a valid application). However, if the application is not valid then the person making the application will be told of the deficiencies and nothing will happen to the application until the missing components are provided. The most common and avoidable causes are:

  1. Failure to supply an XML file of the completed clinical trial application form: the XML file is required to enable the MHRA to enter the details of the trial into the EudraCT database.
  2. Failure to complete sections C1 of the Clinical Trial Authorisation Form or section D1 of the Notification of Amendment Form: the MHRA requires this information in order to be able to communicate with the applicant.
  3. Failure to supply a letter of authorisation from the sponsor: a letter of authorisation is required by the MHRA for the person or organisation named as the applicant to act on behalf of the sponsor.
  4. Failure to provide PDF documents for the protocol, investigator’s brochure, IMP dossier and Summary of Product Characteristics (where appropriate) that have undergone optical character recognition (OCR): all PDF documents should be created directly from Word or undergo Adobe Acrobat optical character recognition at the time of creation.
  5. Password protection on disks: avoid password protecting documents or disks.

Common errors seen on valid CTA applications

According to the MHRA, commonly seen basic deficiencies in CTA applications, requiring the MHRA to issue a request for further information, are as follows :

  1. Manufacturers Authorisation missing or clarification required
  2. Sample labels missing (without justification) or requires revision
  3. QP declarations missing or incomplete, particularly in the case of IMP imports from outside the EU/EEA
  4. SUSAR/ADR provisions missing from the protocol
  5. Protocol inaccuracies
  6. Application form inaccuracies

Further information on validation of CTA applications can be obtained on the MHRA website