Trial Title:
Predicting Incidental Gallbladder Cancer
NCT ID:
NCT06531408
Condition:
Gallbladder Cancer
Conditions: Official terms:
Gallbladder Neoplasms
Conditions: Keywords:
Incidental Gallbladder Cancer
Diagnostic Modelling
Study type:
Observational
Overall status:
Not yet recruiting
Study design:
Time perspective:
Cross-Sectional
Summary:
The goal of this observational study is to identify risks factors for incidental
(unexpected) gallbladder cancer in adult patients undergoing routine gallbladder surgery
(cholecystectomy) for conditions such as gallstones or infection. The main question it
aims to answer is:
Can the investigators use risk factors for incidental gallbladder cancer to develop a
diagnostic score which could be used to stratify the risk of gallbladder cancer in
patients undergoing routine cholecystectomy? Participants undergoing gallbladder surgery
will be identified by surgical trainees and data will be collected about the patients,
their tests and the findings at their operation. The surgical trainees will also collect
the result of any laboratory tests on their gallbladder.
The study will occur in two stages - the first stage, called a feasibility phase, will
test the study design and make sure that it is possible to collect the necessary
information. If this stage is a success then information will be collected from as many
as 30,000 patients.
There will also be an interview-based study running alongside the feasibility phase,
which will explore perceptions of the risk of incidental gallbladder cancer in routine
gallbladder surgery, and whether - with a good diagnostic score - it could be acceptable
to only send high-risk gallbladder's for histopathology.
Detailed description:
This is a cross-sectional study of prospectively identified (identified in advance)
patients undergoing routine gallbladder surgery in the United Kingdom (UK). It will be
undertaken in two phases and has an adaptive design. This means that the results of the
first phase could affect the design of the second phase.
The first phase includes a parallel, interview based study which will explore the risk of
incidental Gallbladder Cancer (iGBC) and establish whether Selective Histological
Analysis (where gallbladders are chosen for post-operative tests based on their
individual risk of iGBC) is acceptable to a representative cohort.
The primary objective of this study is to develop and validate a diagnostic scoring
system for iGBC in UK patients undergoing routine gallbladder surgery. There are two
similar scores in existence, however they have been conducted in a way which means that
their data may be skewed, because they were conducted in countries which already use
selective histological analysis and have very different pathways to cholecystectomy when
compared to the UK. The investigators therefore need to build a new, UK dataset, and the
most reliable way to do this is to intentionally collect all of the required data from a
new set of patients. Often this can be done using patients who have already been treated
- called retrospective (looking backwards) data collection. However, to be a high-quality
dataset requires each patient to consistently have a complete set of data, and the
investigators know that retrospective studies often lead to missing data points.
Additionally, intraoperative findings are always recorded on an operation note, but not
always in a consistent way. By collecting data on patients who will be treated during a
future study period (prospective data collection), the investigators can ask for these
findings to be recorded in a way which is standardised, so they can be reliably compared
between surgeons and hospitals. The investigators have therefore elected to undertake a
prospective study of patients undergoing routine gallbladder surgery.
To identify risk factors for a disease, a sample size which would be expected to give
rise to ten "events", or diagnoses, of interest is typically felt to be required. As iGBC
is thought to be present in about one in every 500 gallbladder operations, this gives a
sample size of 5,000 patients to identify risk factors. However, to develop a model of
the factors which cause the disease, from which a diagnostic scoring system can be
produced, the expected number of diagnostic parameters needed, which may be included in
the scoring system, has to be considered. A diagnostic parameter is a variable, for
example the biological sex of a patient, and each variable is counted at least once. When
a variable has more than two potential options, for example a patient's ethnicity, each
additional option is counted as an extra parameter. The previous diagnostic scores have
used 3-4 diagnostic parameters, however they have lacked the nuance required of the test.
Several of the known and suspected risk factors have more than one potential option, and
after discussion, it was felt that allowing for 20 diagnostic parameters was realistic.
With their statistician, the investigators have calculated a minimum number of fully
completed patient records of just under 21,000. It is unrealistic to expect that every
record will be fully completed, and in line with convention the investigators have
planned for 80% of records to be fully completed. They provisionally, therefore, expect
to require 26,245 patient records to achieve statistical power and will provisionally
target 30,000 to allow expansion as the result of necessary variation from expected
findings which may become evident after the feasibility phase.
Attempting to conduct a study of up to 30,000 patients without proof of concept could
result in a lot of effort without success. Therefore, the investigators have designed a
two-stage study. The first stage will test the feasibility of the whole study and will
consist of a pilot, or "dry run" of the proposed methodology. This dry run will be
conducted across 8 surgical units, from within 7 organisations, and over 6 months will
collect data from as many as 500 patients. This will allow the investigators to assess
whether they can recruit enough patients, quickly enough from the number of participating
sites which are involved to be able to conduct the full study within the proposed
timeframe. It will also establish whether the data which is being collected is
sufficiently complete (i.e. high quality) to be useful if collected from all the patients
needed to develop the diagnostic score. Finally, the investigators will be able to
confirm whether the population they are testing has rates of incidental cancer and other
changes which are in line with published and previously observed rates. Alongside this
pilot study, the investigators will conduct an interview based study to establish how
patients and relevant professionals think about the risk of incidental cancer in routine
cholecystectomy, and what the participants perceive the barriers to and acceptability of
selective histological analysis is.
After the information from the feasibility phase has been collected and analysed, the
outcomes will be assessed and any necessary adaptations made to the study. The study will
only continue beyond this "feasibility" phase if the outcomes show that it can
successfully collect the required data, in the required time frame. This assessment will
be made based on how complete the data returned is, how quickly patients were recruited
to the study, whether there have been difficulties collecting information on important
risk factors (and whether those difficulties can be resolved) and, importantly, whether
the investigators are able to obtain enough funding to collect the data.
Patients in either stage of the main study will be identified on or before the day of
surgery. All of the information which will be collected about them will normally be
gathered in the course of routine care and can be used even when fully de-identified.
Patients will not undergo any changes to their normal care as the study will simply
observe details about them, their operation, their tests, and the result of their
histopathology test. As the study requires so many patients, it is felt that consenting
them will be both highly impracticable and prohibitively expensive. The data will
therefore be collected without specific patient consent, in line with current guidance,
but measures will be taken to inform the patients that the study is ongoing. As the
patients do not need to do anything for the study, the burden on them, or risk to them
will be minimal. A trainee collaborative of surgical doctors will collect the data before
and after the operation and will enter it into a specially designed data collection tool
on a secure platform called REDCap. The REDCap data collection tool allows de-identified
information to be transferred safely between the participating hospital and the central
research team at University Hospitals Plymouth NHS Trust. Data entered will regularly be
reviewed by a researcher from the central team of investigators to identify any outlier
data points early, in order that they can be reviewed before data collection ends. In
order to further confirm the integrity of the data being collected, separate trainees
will be recruited by the principal investigator for each site to act as "data
validators". These trainees will be asked to input duplicate information on a random
selection of the patients recruited at their hospital. This reassessment of the patient
records will help to confirm whether the data being inputted is sufficiently reliable to
be used for the development of a diagnostic test. For the feasibility phase, 10% of
patients will be reassessed, but the percentage of patients undergoing further evaluation
could be reduced in the full study if initial data validation is reassuring.
During the feasibility phase, a doctoral student (who is also a surgical trainee at
University Hospitals Plymouth NHS Trust) will conduct an interview based study, as
mentioned previously. Patients and professional participants will be identified in
participating sites or by direct approach and will be invited to contact the student
using the study email address. Alternatively, at the potential participant's request, the
clinician who identified them may make the initial contact on their behalf. The potential
participant will then be provided with information about the study to consider, and will
have a (usually telephone) conversation with an investigator about what is required of
them and what will happen to the information which the participant provides. The
participant will be invited to sign a consent form, which will preferably be e-consent
(but will have the same content as the paper consent) before they undertake an interview.
The interview will either happen face-to-face or online, and will be recorded. The
recording will be transcribed (turned into a written document) and the transcript will be
de-identified. These transcripts will be analysed using a "pragmatic methodology" in
specialist software. The analysis will break the comments of the participant up into
coded phrases which are then organised into "themes", which can then be analysed between
participants, and participant groups.
Finally, after the feasibility stage is completed, assuming that it shows that the full
study can progress, further funding and site recruitment will be undertaken. The full
study will be carried out much as the pilot study will be carried out. It is important
that the pilot study replicates the full study as closely as possible, so that the rates
of patient recruitment and data completeness are likely to be replicated throughout.
After the full study has been completed, the data generated (including from the pilot
study, unless major alterations have been required) will be analysed in depth, to look
for risk factors for incidental gallbladder cancer. Significant risk factors will be
combined to make a model of the predictive (diagnostic) factors for incidental
gallbladder cancer, and finally a score which could predict the risk of incidental cancer
could be produced. This will be provisionally checked (validated) against the dataset as
"proof" of its quality.
Criteria for eligibility:
Study pop:
Adult patients undergoing cholecystectomy for benign gallbladder diseases (most often
gallstone disease), who do not have a risk of gallbladder cancer which is significantly
higher than the typical patient.
Sampling method:
Probability Sample
Criteria:
Inclusion Criteria:
All adult patients (>=18 years of age) undergoing cholecystectomy (including subtotal and
remnant cholecystectomy) for benign indications:
- Symptomatic Gallstone Disease (includes Gallstone Pancreatitis)
- Biliary Dyskinesia
Exclusion Criteria:
Participants may not enter the study if ANY of the following apply:
- Imaging suspicious for/confirming type III/IV Mirizzi syndrome.
- History of gallbladder or biliary tree malignancies
- Any pre-operative clinical suspicion of Gallbladder or biliary tree malignancy,
(even if subsequently dismissed or disproven)
- Presence of Gallbladder polyps ≥5mm
- Biliary tree abnormalities, including Primary Sclerosing Cholangitis and Choledochal
Cysts
- Patients undergoing cholecystectomy as a part of, or incidental to, another
procedure.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
Accepts Healthy Volunteers
Start date:
September 1, 2024
Completion date:
September 2029
Lead sponsor:
Agency:
University Hospital Plymouth NHS Trust
Agency class:
Other
Collaborator:
Agency:
University of Plymouth
Agency class:
Other
Collaborator:
Agency:
Royal Devon University Healthcare NHS Foundation Trust
Agency class:
Other
Collaborator:
Agency:
Royal Cornwall Hospitals Trust
Agency class:
Other
Collaborator:
Agency:
Torbay and South Devon NHS Foundation Trust
Agency class:
Other
Collaborator:
Agency:
University Hospitals Bristol and Weston NHS Foundation Trust
Agency class:
Other
Collaborator:
Agency:
North Bristol NHS Trust
Agency class:
Other
Collaborator:
Agency:
Gloucestershire Hospitals NHS Foundation Trust
Agency class:
Other
Source:
University Hospital Plymouth NHS Trust
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06531408
