Background
Methods
Eligibility
RCT identification
Data collection and analysis
Patient and public involvement
Results
Results of the search
RCT characteristics
Trial characteristic | Summary extraction: 2013–16, n (%) n = 69 | Detailed extraction: 2017–18, n (%) n = 91 | Total, n (%) n = 160 |
---|---|---|---|
Purpose | |||
Screening | 6 (9%) | 10 (11%) | 16 (10%) |
Treatment | 51 (74%) | 65 (71%) | 116 (73%) |
Primary prevention | 12 (17%) | 16 (18%) | 28 (18%) |
Feasibility/Pilot trial | |||
Yes | 6 (9%) | 11 (12%) | 17 (11%) |
No | 63 (91%) | 80 (88%) | 143 (89%) |
Recruitment setting | |||
Primary care | 23 (33%) | 18 (20%) | 41 (26%) |
Secondary care | 46 (67%) | 73 (80%) | 119 (74%) |
Disease category | |||
Cancer | 17 (25%) | 30 (33%) | 47 (29%) |
Cardiovascular and stroke | 21 (30%) | 25 (27%) | 46 (29%) |
Pregnancy and childbirth | 4 (6%) | 5 (5%) | 9 (6%) |
Mental/neurological health | 6 (9%) | 6 (7%) | 12 (8%) |
Infection | 5 (7%) | 3 (3%) | 8 (5%) |
Endocrine and diabetes | 1 (1%) | 3 (3%) | 4 (3%) |
Inflammatory disorder | 2 (3%) | 3 (3%) | 5 (3%) |
Other | 13 (19%) | 16 (18%) | 29 (18%) |
Intervention | |||
Drug | 38 (55%) | 38 (42%) | 76 (48%) |
Surgical | 5 (7%) | 8 (9%) | 13 (8%) |
Other | 26 (38%) | 45 (49%) | 71 (44%) |
Primary outcome | |||
Survival related | 33 (48%) | 39 (43%) | 72 (45%) |
Other | 36 (52%) | 52 (57%) | 88 (55%) |
Randomisation | |||
Individual | 61 (88%) | 75 (82%) | 136 (85%) |
Cluster | 8 (12%) | 16 (18%) | 24 (15%) |
Trial size | |||
Median | 1103 | 2611 | 1590 |
Range | 41–170,432 | 53–6,000,000 | 41–6,000,000 |
1–500 | 21 (30%) | 20 (22%) | 41 (26%) |
500–5000 | 31 (45%) | 43 (47%) | 74 (46%) |
>5000 | 17 (25%) | 25 (27%) | 42 (26%) |
Unclear | 0 (0%) | 3 (3%) | 3 (2%) |
International accrual | |||
Yes | 13 (19%) | 19 (21%) | 32 (20%) |
No (UK only) | 56 (81%) | 69 (76%) | 125 (78%) |
Unclear | 0 (0%) | 3 (3%) | 3 (2%) |
Coordinated by registered clinical trials unit | |||
Yes | 40 (58%) | 63 (69%) | 103 (64%) |
No | 10 (14%) | 12 (13%) | 22 (14%) |
Unclear | 19 (28%) | 16 (18%) | 35 (22%) |
Highest profile journal (if primary report published) | |||
BMJ | NA | 2 (2%) | 2 (1%) |
JAMA | NA | 6 (7%) | 6 (4%) |
Lancet | NA | 16 (18%) | 16 (10%) |
Lancet-specialty | NA | 2 (2%) | 2 (1%) |
NEJM | NA | 3 (3%) | 3 (2%) |
Other | NA | 6 (7%) | 6 (4%) |
Not yet published | NA | 56 (62%) | 56 (35%) |
Not captured | 69 (100%) | NA | 69 (43%) |
RCTs accessing RCHD (n = 160) | HRA in 2015a (n = 963b) | |
---|---|---|
Recruitment setting | ||
Primary care | 41 (26%) | 48 (5%) |
Secondary care | 119 (74%) | 846 (95%) |
Unclear/missing | 0 | 69 |
Therapeutic area | ||
Cancer | 47 (29%) | 168 (17%) |
Cardiovascular and stroke | 46 (29%) | 121 (13%) |
Pregnancy and childbirth | 9 (6%) | 30 (3%) |
Infection | 8 (5%) | 55 (6%) |
Inflammatory disorder | 5 (3%) | 72 (7%) |
Drug trial | 76 (48%) | 515 (53%) |
Randomisation | ||
Individual | 136 (85%) | 934 (97%) |
Cluster trial | 24 (15%) | 29 (3%) |
Feasibility/pilot | 17 (11%) | 177 (18%) |
Sample size (median, range) | 1590 (41–6,000,000) | 275 (6–30,000) |
Unclear/missing | 0 | 440 |
Recruitment location | ||
UK only | 125 (78%) | 450 (50%) |
International trials | 32 (20%) | 443 (50%) |
Unclear/missing | 0 | 70 |
RCHD access and use
Registry | Total trialsn = 160 | Total trials (2017–2018) n = 91 | Datasets accessed Total trials (2017–2018) n = 91 | |||
---|---|---|---|---|---|---|
Death n = 69 | Hospital visits n = 50 | Cancer registration n = 29 | Other n = 26 | |||
NHS Digital | 108 (68%) | 59 (65%) | 58 (84%) | 34 (68%) | 22 (76%) | 4 (15%) |
ISD-Scotland | 35 (22%) | 25 (27%) | 16 (23%) | 13 (26%) | 7 (24%) | 2 (8%) |
PHE | 15 (9%) | 11 (12%) | 3 (4%) | 6 (12%) | 10 (34%) | 1 (4%) |
SAIL | 9 (6%) | 6 (7%) | 2 (3%) | 5 (10%) | 2 (7%) | 1 (4%) |
ICNARC | 7 (4%) | 4 (4%) | 1 (1%) | 0 (0%) | 0 (0%) | 4 (15%) |
NWIS | 7 (4%) | 6 (7%) | 1 (1%) | 6 (12%) | 1 (3%) | 0 (0%) |
PICANet | 6 (4%) | 2 (2%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (8%) |
CPRD | 4 (3%) | 1 (1%) | 0 (0%) | 1 (2%) | 0 (0%) | 1 (4%) |
NHSBT | 3 (2%) | 3 (3%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (8%) |
TARN | 3 (2%) | 2 (2%) | 1 (1%) | 1 (2%) | 0 (0%) | 2 (8%) |
NELA | 2 (1%) | 2 (2%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (8%) |
NNRD | 2 (1%) | 2 (2%) | 1 (1%) | 1 (2%) | 0 (0%) | 2 (8%) |
PHW | 2 (1%) | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (4%) |
UKRR | 2 (1%) | 2 (2%) | 0 (0%) | 1 (2%) | 1 (3%) | 0 (0%) |
ResearchOne | 2 (1%) | 2 (2%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (8%) |
DOH | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
FFFAP | 1 (1%) | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (4%) |
HBS | 1 (1%) | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (4%) |
NICOR | 1 (1%) | 1 (1%) | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) |
NICR | 1 (1%) | 1 (1%) | 0 (0%) | 0 (0%) | 1 (3%) | 0 (0%) |
OHCAO | 1 (1%) | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (4%) |
UKCFR | 1 (1%) | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (4%) |
Data use category | Description | Example | All trials N = 91 | Primary N = 74 | Long-term follow-up N = 52 | Both N = 36 |
---|---|---|---|---|---|---|
1 | The RCHD alone is used as trial data, and there is no cross-checking or comparison against any other data. | One of the included RCTs was a cluster-randomised trial of GP practices. Outcome data specific to the trial were extracted at the level of the cluster (GP practice) from CPRD. | 52 (57%) | 33 (45%) | 34 (65%) | 15 (42%) |
2 | RCHD is used to cross-check against or verify known trial data, namely data already being collected on CRFs as part of the trial (arising from clinical observations and measurements). | In one case, death and cause of death of participants are captured on CRFs at each site. NHS Digital also sends the trial team quarterly reports of all new deaths. The trial team then compares the events and cause of death from both sources. | 27 (30%) | 24 (32%) | 6 (12%) | 3 (8%) |
3 | RCHD is used to cross-check against or verify self-reported trial data, namely data already being collected from participants, such as by questionnaire. | In one trial, participants are asked to complete a questionnaire every 3 months which asks whether they had any unexpected stays in hospital. This information is cross-checked against Hospital Episode Statistics data obtained from NHS Digital. | 28 (31%) | 22 (30%) | 11 (21%) | 5 (14%) |
4 | RCHD is used to alert or flag trial teams to a potential outcome/event, prompting medical note review to confirm the outcome/event. The specific outcome/events being flagged are not otherwise being captured as trial data. This may be accompanied by clinical end-point review or adjudication of events and outcomes. | In one RCT, participants were flagged in the UK Transplant Registry for notification of transplant rejection and failure. When participants were identified as having a transplant rejection or failure, study staff sought extra information from hospital records. The collated information was redacted and used for central adjudication by trained clinicians. | 22 (24%) | 19 (26%) | 9 (17%) | 6 (17%) |
5 | RCHD from one source is used to cross-check against or compared with RCHD from another source. | One of the included RCTs accessed RCHD from NHS Digital, ICNARC and OHCAO, and all had provided the same fields, such as length of stay in intensive care. | 9 (10%) | 7 (9%) | 6 (12%) | 4 (11%) |
6 | RCHD is being used for health economic analysis or cost-effectiveness purposes, rather than a clinical outcome. | In one study, Hospital Episode Statistics data were used to calculate the cost of secondary resource use within 90 days of randomisation. | 25 (27%) | 21 (28%) | 12 (23%) | 8 (22%) |
7 | RCHD is not used directly for trial purposes but to evaluate the quality of these data compared with trial data or other RCHD, or RCHD is used to generate an algorithm or equation that hopes to predict or replicate the frequency of events/outcomes. | In a breast cancer trial, cancer data from NCRAS were accessed and compared against the trial data to assess the completeness, validity and consistency of the two data sources. | 11 (12%) | 11 (15%) | 1 (2%) | 1 (3%) |
Unclear | – | – | 13 (14%) | 9 (12%) | 9 (17%) | 5 (14%) |
Discussion
Conclusion
Barrier | Example/explanation | Potential solution |
---|---|---|
Lack of comprehensive list of RCHD sources and the data they hold | There is no one point where you can find out about all sources of RCHD. | A searchable database – HDR UK or NHS Digital is responsible for update. |
Clear terminology to describe data from registries | The source of the trial data is not always mentioned in trial publications. | Publication of consensus terminology and a description of the way in which RCHD can be used. |
Publications of trials using RCHD did not make mention of it. | In methods section, details of the sources of RCHD should be stated. | Soon-to-be-released EHR CONSORT extension for routinely collected health data should improve this. |
Lack of awareness by trialists of the availability and utility of RCHD | Shown by a small percentage of trials using RCHD | More publicity on available RCHD and the use of RCHD |
Poor accessibility of data | Registry name change invalidating consent Long delays of several years in application process RCHD not provided despite agreement | Streamline the RCHD application process and render it efficient. |
Poor data retention and no possibility of onward sharing | Time limit to keeping the data is shorter than the data storage time limit for the trial. Data sharing is often necessary to achieve funding for a trial. | RCHD needs to align with trial data retention rules and data-sharing requirements. |
Data quality and timeliness | Trial data are monitored and checked and a lot of registry data are not. | Registry data need a validation process to ensure that their RCHD can be used as a verifiable GCP-compliant data source. A comparison of trial and registry data in several trials, facilitated by a SWAT, is required to educate all about the accuracy and completeness of registry data. |
Regulator ready RCHD | Trial data require underlying source data whilst registry data are not source data and do not often have checked underlying source data. | Regulators and registries need to agree a solution to underlying source data. |