Postoperative Outcomes Within an Enhanced Recovery After Surgery Protocol
Condition: Perioperative Care; Postoperative Complications; Colorectal Surgery; Critical Pathways
MeSH terms: Postoperative Complications
Study type: Observational [Patient Registry]

Summary: 
      Short title POWER Audit

      Methods 60 days national (Spain) audit of postoperative complications following elective
      gastrointestinal surgery within an enhanced recovery after surgery (ERAS) protocol.

      Research sites Hospitals undertaking elective lower gastrointestinal surgery. Objective To
      provide detailed data describing post-operative complications and associated mortality; and
      length of stay.

      To provide detailed data describing adherence to ERAS protocol and its association to
      morbidity.

      Number of patients Not specified. All eligible patients undergoing surgery during the study
      month. Inclusion Criteria All adult patients (aged ≥18 years) undergoing lower
      gastrointestinal elective surgery within an ERAS protocol during the 60 day study period.

      Statistical analysis Univariate analysis will be used to test factors (patient, surgical, and
      ERAS related) associated with surgical complications, length of stay (LOS) and in-hospital
      death. Single and multi-level logistic regression models will be constructed to identify
      factors independently associated with these outcomes and to adjust for differences in
      confounding factors. A stepwise approach will be used to enter new terms. A single final
      analysis is planned at the end of the study.

      Summary statistics with post hoc Bonferroni corrections will be used to assess possible
      dose-response dependence in percentage of patients with postoperative complications and LOS.

      Proposed Start Date A 60 day period between 2017

      Proposed End Date

      Data collection will end by September 2017

      Study Duration Six months
    

Detailed description: 
      Study data Data will be collected on all eligible patients who undergo elective lower
      gastrointestinal surgery within any compliance of an ERAS protocol during the study months.
      Only routine clinical data will be included and where this is unavailable the domain will be
      left blank e.g. patients who do not require blood tests. It is possible that regional groups
      may supplement their core data set with a very limited number of additional variables if
      these can be accommodated within the two page case record form (CRF) and they comply with
      regulations applied to this study.

      Data collection Data will be collected in individual hospitals on a paper CRF for each
      patient recruited. Paper CRFs will be stored within a locked office in each centre. This will
      include identifiable patient data in order to allow follow-up of clinical outcomes. Data will
      then be pseudo-anonymised by generating a unique numeric code and transcribed by local
      investigators onto an internet based electronic CRF. Each patient will only be identified on
      the electronic CRF (eCRF) by their numeric code. Thus the co- ordinating study team cannot
      trace data back to an individual patient without contact with the local team. A patient list
      will be used in each centre to match identifier codes in the database to individual patients
      in order to record clinical outcomes and supply any missing data points. Once the local
      co-ordinator confirms data entry is complete for their hospital they will receive a
      spreadsheet of raw (un-cleaned) data, allowing further checks for data completeness and
      accuracy.

      Audit organisation

      POWER will be led by the study management group who will be responsible for study
      administration, communication between project partners, data collation and data management.
      Regional co-ordinators will lead the project in each Spanish region and:

        -  Identify local co-ordinators in participating hospitals

        -  Assist with translation of study paperwork as required

        -  Ensure distribution of study paperwork and other materials

        -  Ensure necessary regulatory approvals are in place prior to the start date

        -  Ensure good communication with the participating sites in his/her region

      Local co-ordinators in individual institutions will have the following responsibilities:

        -  Provide leadership for the study in their institution

        -  Ensure all relevant regulatory approvals are in place for their institution

        -  Ensure adequate training of all relevant staff prior to data collection

        -  Supervise daily data collection and assist with problem solving

        -  Act as guarantor for the integrity and quality of data collected

        -  Ensure timely completion of eCRFs by supervising local data entry

        -  Communicate with the relevant national co-ordinator

      End of Study Definition The end of the study is defined as the end of the 30-day follow-up
      for the last patient included. Data analysis shall follow this.

      STATISTICAL ANALYSIS

      Sample size calculation Our plan is to recruit as many centres as possible on an
      international basis and ask them to include all eligible patients in the study. Only centres
      including 10 valid patients will be included in the data analysis. We do not have a specific
      sample size and statistical models will be adapted to the event rate provided by the sample
      recruited.

      However, a minimum sample size is estimated, expecting 50% of patients with at least one
      complication, which is the data that requires a higher sample-size with a confidence level of
      95% and an accuracy of 3%, a total of 1068 patients. A larger sample size, greater accuracy
      will be achieved.

      Statistical analysis Hospitals including data describing less than 10 valid patients will be
      excluded in the data analysis. Data will be presented in individual regions. All regional and
      institutional level data will be anonymised prior to publication. Categorical variables will
      be described as proportions and will be compared using chi-square or Fisher's exact test.
      Continuous variables will be described as mean and standard deviation, if normally
      distributed, or median and inter-quartile range, if not normally distributed. Comparisons of
      continuous variables will be performed using one-way ANOVA or Mann-Whitney test as
      appropriate. Univariate analysis will be performed to test factors associated with
      post-operative complications, LOS and in-hospital death. Single-level and hierarchical
      multi-level logistic regression models will be constructed to identify factors independently
      associated with these outcomes and to adjust for differences in confounding factors. Factors
      will be entered into the models based on their univariate relation to outcome (p<0.05),
      biological plausibility and low rate of missing data. A stepwise approach will be used to
      enter new terms. Results of logistic regression will be reported as adjusted odds ratios (OR)
      with 95% confidence intervals. The models will be assessed through the use of sensitivity
      analyses to explore possible interacting factors and examine any effect on the results. A
      single final analysis is planned at the end of the study.

      Overall compliance will be calculated as the average of all pre- and intraoperative ERAS
      adapted elements, as specified in the ERAS society colon and rectal guidelines. For
      exploratory purposes, post-ERAS patients' guideline compliance will be categorised into
      quintiles: compliance <45% (compliance 1), compliance 45-55 % (compliance 2), compliance
      55-65 % (compliance 3), compliance 65-75 % (compliance 4) and compliance >75 % (compliance
      5). Summary statistics with post hoc Bonferroni corrections will be used to assess possible
      dose-response dependence in percenctage of patients with postoperative complications and LOS.

      The data set will be analyzed using the percentage of patients with postoperative
      complications and LOS the main and secondary outcome variables. The influence of the
      following factors was assessed: sex, age, American Society of anesthesia (ASA) status, body
      mass index (BMI), preoperative hemoglobin, comorbidity, including hypertension , diabetes
      mellitus, coronary arterial disease , chronic obstructive pulmonary disease, and chronic
      renal disease; surgical approach (open, laparoscopic), duration of surgery, intraoperative
      fluid administration and first 24 hours fluid balance; and individual components of the ERAS
      protocol. Univariate analysis will be initially undertaken to assess the relationship between
      each factor and the outcome variables. Comparisons will be made using the χ2 test for all
      categorical variables and the t test and Kruskal-Wallis test will be used to evaluate
      differences between continuous normally and non-normally distributed variables, respectively.
      Owing to its non-normal distribution, LOS will be analyzed by log-normal transformation and
      independent t tests with back exponentiation. Multivariate analysis, using binary logistic
      regression for development of complications and linear regression of log transformed length
      of LOS, will be then performed for all variables in the univariate analysis with a
      significant or near-significant difference (P < 0.1). P < 0.05 will be considered
      statistically significant.

      Primary outcome measure

      The percentage of patients who developed pre-defined mild-moderate-severe postoperative
      complications in the 30 days after surgery, including complications that occurred before
      hospital discharge and those that happened after discharge and required ambulatory or
      in-hospital care. Postoperative complications are defined according standards for definitions
      and use of outcome measures for clinical effectiveness research in perioperative medicine
      (EPCO).

      Secondary outcome measures

        -  In-hospital all-cause mortality (censored at 30 days following surgery)

        -  Adherence to ERAS items (within 30 days following surgery)

        -  Duration of hospital stay (duration of primary hospital stay after surgery)

      ETHICS The principal investigator must ensure that the study will be carried out in
      accordance with the ethical principles in the Research Governance Framework for Health and
      Social Care, Second Edition, 2005 and its subsequent amendments as applicable and applicable
      legal and regulatory requirements. Research ethics approval may not be required in all
      participating nations. Regional and local investigators will be responsible for clarifying
      the need for ethics and other regulatory approvals and for ensuring these are in place prior
      to data collection. Centres will not be permitted to record data without providing
      confirmation that the necessary ethics or other regulatory approvals are in place. There will
      be no requirement for individual patient consent as all data will be anonymised and are
      already recorded as part of routine clinical care.

      SAFETY CONSIDERATIONS There are no safety considerations relating to the POWER Audit . There
      is no risk of harm to either patients or investigators.

      DATA HANDLING AND RECORD KEEPING All identifiable data collected, processed and stored for
      the purposes of the project will remain confidential at all times and comply with Good
      Clinical Practice for research (GCP) guidelines and the principles of the Data Protection Act
      1998 (UK). Each centre will maintain a trial file including a protocol, local investigator
      delegation log, documentation of the relevant regulatory approvals and patient list. POWER
      data collection sheets will be stored securely in a locked cupboard and handled only by
      clinical staff familiar will handling personal data and with Good Clinical Practice for
      research. Data will be anonymised prior to transfer to the POWER Audit management group
      except where the patient has given written informed consent to allow transfer of identifiable
      data. Access to the data entry system will be protected by username and password, delivered
      during the registration process for individual local investigators. All electronic data
      transfer between participating centres and the coordinating centre will be encrypted. Desktop
      and laptop security will be maintained through user names and passwords. All local
      investigators will be asked to undergo training in accordance with the Research Governance
      Framework. The study master files will be stored in an approved repository for 20 years
      following the end of the study

      SAFETY REPORTING The trial involves negligible risks to patients and investigators. Adverse
      events will not be monitored or reported.

      MONITORING & AUDITING POWER Audit master documents will be audited by the sponsor ("Grupo
      Español de Rehabilitación Multimodal", (GERM)) to ensure study activities are conducted
      according to the protocol, the sponsor's standard operating procedures, Good Clinical
      Practice and the applicable regulatory requirements. In participating hospitals, local study
      documents may be selected for audit on a local basis. However, the POWER Audit team will not
      routinely monitor data collection in individual hospitals or conduct source data
      verification.

      TRIAL COMMITTEES Trial Management Group The POWER Audit will be managed by the GERM Network
      and by the "Evidence Anesthesia Review Group (EAR)" team based at Complutense University of
      Madrid. The day-to-day conduct of the trial will be led by the trial management group,
      chaired by Javier Ripollés-Melchor.

      Trial Steering Committee The trial steering committee will be appointed with an independent
      chairperson (José Manuel Ramírez), lay representation and independent members. There is no
      role for a Data Monitoring Committee.

      FINANCE AND FUNDING The POWER Audit is funded by an unrestricted research grant from GERM
      Network ("Grupo Español de Rehabilitación Multimodal"). The funder will play no role in study
      design, conduct, data collection, data analysis, reporting or interpretation of the results.

      INDEMNITY The POWER Audit is sponsored by GERM Network ("Grupo Español de Rehabilitación
      Multimodal") who has appropriate indemnity arrangements in place.

      DISSEMINATION OF RESEARCH FINDINGS The steering committee will appoint a writing committee to
      draft the scientific report(s) of this investigation, which will be disseminated in a timely
      manner. It is anticipated that a number of secondary analyses will be performed. POWER
      investigators will be given priority to lead such analyses and are encouraged to do so.
      Participation and authorship opportunities will be based on contribution to the primary
      study. The steering committee will consider the scientific validity and the possible effect
      on the anonymity of participating centres prior to granting any such requests. Where
      necessary, a prior written agreement will set out the terms of such collaborations. The
      steering committee must approve the final version of all manuscripts including POWER data
      prior to submission. In the event of disagreement within the steering committee, the chief
      investigator will make a ruling. Any analysis incorporating POWER data from two or more study
      sites will be considered a secondary analysis and subject to these rules. The e CRF will
      provide local co-ordinators with the raw (un-cleaned) data for their centre once they have
      confirmed this to be both complete and accurate.

      Data management and ownership The study sponsor, "Grupo Español de Rehabilitación
      Multimodal", will act as custodian of the data. In line with the principles of data
      preservation and sharing, the steering committee will, after publication of the overall
      dataset, consider all reasonable requests to conduct secondary analyses. The primary
      consideration for such decisions will be the quality and validity of any proposed analysis.
      Only summary data will be presented publicly and all national, institutional and patient
      level data will be strictly anonymised. Individual patient data provided by participating
      hospitals remain the property of the respective institution. Once each local co-ordinator has
      confirmed the data provided from their hospital are both complete and accurate, they will be
      provided with a spreadsheet of the raw (un-cleaned) data for their hospital. The complete
      POWER dataset, anonymised with respect to participating patients, hospitals and nations, will
      be made freely and publicly available two years following publication of the main scientific
      report. Prior to this, the steering committee is not under any obligation to release data to
      any collaborator or third party if they believe this is not in keeping with the wider aims of
      the POWER Audit.
    

Intervention name(s): Colorectal Surgery
Intervention type(s): Procedure
Intervention description(s): Postoperative Audit
Observational model: Other
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        All adult patients (aged ≥18 years) undergoing elective lower gastrointestinal surgery
        within any compliance of an ERAS protocol (including patients with 0 compliance) in a
        participating hospital during the 60-day cohort period with a planned overnight stay.