NHS Digital Data Release Register - reformatted
Medical Research Council Clinical Trials Unit
Project 1 — DARS-NIC-37191-P5S9S
Opt outs honoured: No - consent provided by participants of research study (Reasonable Expectation, Consent (Reasonable Expectation))
When: 2017/12 — 2020/01.
Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 – s261(2)(c)
- MRIS - Flagging Current Status Report
- MRIS - Cause of Death Report
- MRIS - Cohort Event Notification Report
The RADICALS clinical trial protocol contains two clinical trials for men who have chosen surgery as their primary treatment for prostate cancer. These trials are RADICALS-RT, testing whether a certain subgroup of men should or should not have radiotherapy after their surgery; and RADICALS-HD testing whether men should have hormone therapy (and, if so, how long) with post-operative radiotherapy. The first consent for the trial was taken in November 2007. A total of 2,863 patients were recruited in England & Wales. The primary outcome measure for RADICALS-RT is freedom-from-distant-metastases. The primary outcome measure for RADICALS-HD is survival without death from prostate cancer. These patients, overall, will do well and most men will survive a long time without any failure. The Medical Research Council Clinical Trials Unit (MRC CTU) at University College London (UCL) is concerned that sites will not be able to follow patients as intensely as required over this full period. Flagging data from NHS Digital will allow MRC CTU to ensure that most deaths are captured and included and will also help with cause of death review. MRC CTU is aware that flagging data has been very valuable in previous RCTs. Furthermore no man should die from prostate cancer without prior progression so a reported death will allow MRC CTU to check that events are not being missed on the Case Report Forms that clinicians are directly completing for these consenting patients. MRC CTU will also, for the purposes of survival analysis, be able to assume that patients are alive at a set point in time if not reported dead, thereby increasing reliability of data. Finally, based on previous discussions with ONS statisticians MRC CTU will make assumptions about the survival of patients not reported as dead. For information, there is intention to request HES data to be linked to this request at a later date which would allow MRC CTU to further understand the treatment patterns for the cohort. This will be subject to a new application to NHS Digital.
Comparison of ONS data with deaths of patients reported by study sites has shown that in most cases the study sites have reported deaths in a timely and accurate manner. A small number of discrepancies in cause of death have been identified and corrected through liaison with staff at sites, in each case so far these have been patients who died outside hospital and hospital staff had been uncertain about cause of death. The reassurance of well-reported data coming from study sites has helped the trial management group in planning the future of the trial.
The RADICALS trial will define standard-of-care for men with localized prostate cancer who have chosen surgery. The results are keenly awaited by the uro-oncology community. In no way will the results of the analysis or the dissemination of findings be influenced by MRC CTU's funding organisations. The trial is looking to see whether particular treatment approaches improve long-term disease-based outcomes, notably based in survival or distant spread of the disease. The trial will standardise the use (or otherwise) of immediate post-operative radiotherapy and the use (and duration, or otherwise) or hormone therapy with any post-operative radiotherapy. This patient group will generally do very well and it is key that MRC CTU do not have missing event data. However, long-term follow-up is very difficult in trials; MRC CTU anticipate that some centres will not be able to follow patients adequately. Therefore, connection to flagging data will ensure that MRC CTU do not miss deaths from the analyses. Knowing the status of patients will help MRC CTU to better tailor requests to centres for current information. Furthermore, attributing cause of death is notoriously difficult for men with prostate cancer. Having death registry information will help with MRC CTU's review of causes. Also , if patients are reported to have died from prostate cancer without a prior report of metastases MRC CTU can ensure sites providing this missing information (no man should die from prostate cancer without it first spreading). Regardless of the findings for any of the three main comparisons, MRC CTU will be asked about treatment(s) at relapse(s). MRC CTU have deliberately collected little information on this from sites, preferring to seek this information from central sources. RADICALS is expected to define standard of care in two aspects of prostate cancer treatment where differing practice has arisen in the absence of definitive randomised evidence. International coordination with other large trials is already in place and a meta analysis has been planned in which RADICALS will play a central part.
Intermediate trial reports will be produced for review by the Independent Data Monitoring Committee (IDMC) which is an independent group of experts who monitor patient safety and treatment efficacy data. The IDMC usually meets annually. Reports to the committee are confidential and the IDMC are the only people to see data by randomised group while the trial is in progress. They may recommend changes to the trial, for action by the trial steering committee. For clarification, no data supplied by NHS Digital would be shared with the IDMC. Peer reviewed publications and high impact medical journals -either cancer-specific journal (like JCO or Lancet Oncology) or a general medical journal (like Lancet, JAMA, NEJM). MRC CTU will look to general journals first but will review the results and whether they might or might not appeal to a general audience. It is hoped that the two comparisons for RADICALS-HD will be ready to be reported in Autumn 2017 and 2018 for short-term hormone therapy versus long-term hormone therapy, and no hormone therapy versus short-term hormone therapy respectively. RADICALS-RT should be ready for reporting in Autumn 2020. MRC CTU will communicate the RADICALS results using at least: • Presentation at major international and national scientific conferences • Publication in high-impact peer-reviewed journals • A written summary of results distributed to participants • News articles on MRC CTU website • Tweets on the @MRCCTU Twitter account MRC CTU will also communicate the results to the wider patient population via articles in the Tackle Prostate newsletter, Prostate Matters. MRC CTU will also inform Prostate Cancer UK of the results, building on the relationship MRC CTU have with them for other trials in MRC CTU's prostate cancer portfolio. If appropriate, MRC CTU will work with the MRC and UCL press offices to develop press release(s) about the results. Depending on what the results show, MRC CTU may also look at other methods of communication. For previous prostate cancer trials MRC CTU have used films, briefing papers and events to communicate the results to health-workers and patients. All outputs will be aggregated will small numbers suppressed and in line with the HES Analysis Guide.
The data will be used for the long-term assessment of men in both the RADICALS-RT and RADICALS-HD comparisons of the RADICALS trial protocol. The main outcome measures involved survival and cause of death, which are predefined in both the protocol and the Statistical Analysis Plan. This data will be joined with the data that are requested on the study Case Report Forms and will be linked to those records already held on consenting trial participants. The number of participants and the rationale for their inclusion will always be included in all presented results. 1. The trial team will supply a list of cohort identifiers to NHS Digital containing Trial Number, NHS Number, Date of Birth, full names and postcode. 2. NHS Digital will use the supplied information to extract death information and send back reports using the specified transfer method. The reports will contain the Trial Number, Date of Death if applicable and no other identifiers. 3. Using the secure PID database, the Head of DMS will link these records back to the study-specific trial number and prepare an output file for trial statisticians containing no identifiers other than the full date of death. 4. This output file is placed in a secure directory with access limited only to people listed in the Data Sharing Agreement, all of whom are substantive employees of UCL. 5. Trial statisticians undertake data cleaning/validation activities. 6. The data extract received from NHS Digital then serves three aspects: -i. Deaths already reported to MRC CTU by site – MRC CTU would use NHS Digital data to verify and corroborate date and cause; -ii. Deaths not reported to MRC CTU by site – MRC CTU then follow up with site to corroborate date and cause, to add to study database; -iii. Deaths not reported by site that sites are not aware of (died elsewhere) – in these cases, NHS Digital data becomes the date and cause for entry into MRC CTU’s study database. All processing of ONS data is in accordance with standard ONS terms and conditions. Only substantive employees of UCL will access record level data or aggregated data containing small numbers. No data provided by NHS Digital will be shared with any third parties, including members of the IDMC, except in the form of aggregated data with small numbers suppressed in line with the HES Analysis Guide.