Patients' Conscious Experience and Psychological Consequences of Awake Surgery for Intracerebral Lesions
Condition: Fear; Anxiety; Stress
Study type: Observational

Summary: 
      This study aims to investigate patients' experience of awake surgery of the brain. Patients
      therefore must suffer a disease that makes the technique of awake craniotomy necessary.

      In more detail, the investigators are performing this study in order to investigate the
      influence of fear on pain perception during surgery for patients undergoing awake surgery for
      lesions within the brain. In the event of finding a correlation between fear of the surgery
      and intraoperative pain perception, the investigators aim to reduce possible fear beforehand.

      An additional goal of the investigators is to identify psychological consequences of awake
      craniotomy timely and admit patients to an adequate therapy if necessary.

      There will be no changes regarding the actual treatment of the disease. In case of a consent,
      the patient will receive questionnaires at three timepoints: 1. day before surgery. 2. third
      day after surgery. 3. at 3-6 months postoperatively at the outpatient clinics.

      The benefit of participating in this study is the possibility of detecting psychological
      consequences of awake craniotomy at an early stage. If required, patients will then receive
      treatment timely.

      There are no additional risks. Theoretically there is only a data risk after analysis.

      Patients are free to decide if they want to participate within this study. There are no
      changes in the actual treatment if patients deny participation. In case of participation,
      patients have the right to quit at any time with no reasoning at all.

      During the study investigators are collecting health-related data. If patients quit before
      the study end, data will still be used in pseudonymized form. After 10 years, data will be
      destroyed.

      In case of participation the only duty for the patient is to fill out the questionnaires at
      the above mentioned three time points.

      The investigators conduct this study based on all rules of law regarding data protection.
      Investigators only use the collected data in relation to this study. All investigators are
      under obligation to secrecy.
    

Detailed description: 
      ETHICAL AND REGULATORY ASPECTS

      Ethical Conduct of Study

      The research project will be carried out in accordance to the research plan and with
      principles enunciated in the current version of the Declaration of Helsinki (DoH), the
      Essentials of Good Epidemiological Practice issued by Public Health Switzerland (EGEP), the
      Swiss Law and Swiss regulatory authority's requirements as applicable. The EC and regulatory
      authorities will be informed about project start and termination.

      The Project Leader of this Project Leader initiated Trial acknowledges his responsibilities
      as both the Investigator and the Project Leader.

      Risk categorisation

      Risk category A: Enroled patients are not exposed to additional risks, as intraoperative
      mapping of brain functions using electrical stimulation in awake patients is actually
      considered the gold standard of treatment in intracerebral lesions in the immediate vicinity
      or within eloquent brain regions.

      Ethics Committee (EC)

      Before the project will be conducted, the project plan, the proposed participant information
      and consent form as well as other project-specific documents shall be submitted to a
      competent Ethics Committee (EC). The regular end, premature end or interruption of the
      research project is reported to the EC within 90 days upon completion of the project (HRO
      Art. 22).

      Participant Information and Informed Consent

      Consecutive ongoing recruitment through investigator(s) in daily clinical practice
      (consultations). The subjects will receive the consent form with an address and phone number
      indicated where further questions regarding the study can be discussed directly with the
      project leader. This will take place at least one week before the hospitalisation.

      Participant privacy and safety

      The Project Leader affirms and upholds the principle of the participants' right to dignity,
      privacy and health and that the project team shall comply with applicable privacy laws.
      Especially, anonymity of the participants shall be guaranteed when presenting the data at
      scientific meetings or publishing them in scientific journals.

      Individual participant medical information obtained as a result of this research project is
      considered confidential and disclosure to third parties is prohibited. Participant
      confidentiality will be further ensured by utilising identification code numbers to
      correspond to medical information in the computer files.

      For data verification purposes, authorised representatives of the Project Leader, a competent
      ethics committee may require direct access to parts of the medical records relevant to the
      project, including participants' medical history.

      Early termination of Project

      The Project Leader (and any competent authority) may terminate the project prematurely
      according to certain circumstances (insufficient participant recruitment, change of project
      leader or any other reason that would prevent the project execution according to the research
      plan). The premature end or interruption of the research project would be reported to the EC
      within 90 days upon completion of the project (HRO Art. 22).

      Amendments, Changes

      Significant changes to the project plan would be communicated to relevant parties (e.g.,
      investigators, EC). The Project Leader would submit to the EC any application documents,
      which are affected by the change. At the same time, the project leader would provide
      information on the reasons for the change. Substantial amendments are only implemented after
      approval of the EC.

      BACKGROUND

      Intraoperative mapping of brain functions using electrical stimulation in awake patients has
      been proven to be a safe technique that enables increased tumor removal while preserving the
      functional status of the patients. Former studies reported that the conscious experienced
      procedure is generally well tolerated and psychological sequelae due to awake craniotomy seem
      to be rare (Milian et al., 2014). Fear, anxiety and pain are the most commonly seen phenomena
      intraoperatively (Milian et al., 2014). It is also known that fear and anxiety may aggravate
      pain perception (Keefe et al., 2001). The investigators hypothesize that patients with less
      preoperative anxiety experience less intraoperative pain.

      Rationale for the research Project

      Potential postoperative psychological sequelae could be considered and affected patients
      could benefit of early recognition and treatment.

      Risk-Benefit Assessment

      Enroled patients are not exposed to additional risks, as intraoperative mapping of brain
      functions using electrical stimulation in awake patients is actually considered the gold
      standard of treatment in intracerebral lesions in the immediate vicinity or within eloquent
      brain regions. Potential postoperative psychological sequelae could be considered and
      affected patients could benefit of early recognition and treatment.

      PROJECT DESIGN

      Type of research and general project design

      Research project in which health-related personal data is collected. Data will be
      pseudonymized. Prospective, monocentric, descriptive, cohort study. Overall study duration
      will be about one year. Patients are recruited at the investigators in daily clinical
      practice, which can be days to weeks prior to surgery. Once the surgery is started the study
      duration for each patient will last 6 months post-surgery.

      Procedures

      Standardized questionnaires will be completed by the selected patients as follows:

      1st day preoperatively: MMSE, NRS-anxiety, HADS-D, PDS-1, BPI, PHQ-D, BDI. Intraoperatively:
      NRS for anxiety and pain at three timepoints during surgery: before skin incision, after
      removal of the bone flap, after tumor resection.

      3rd day postoperatively: HADS-D, PHQ-D, PDS-1, BPI, NRS for pain. 6 months postoperatively at
      the outpatient clinics: PHQ-D, BDI, HADS-D, PDS-1, BPI.

      Recruitment and Screening

      Consecutive ongoing recruitment through investigator(s) in daily clinical practice
      (consultations). The subjects will receive the consent form with an address and phone number
      indicated where further questions regarding the study can be discussed directly with the
      project leader. This will take place at least one week before the hospitalisation.

      Methods of minimising bias

      The use of validated questionnaires. Blinding is not necessary as there are no
      randomized/different therapies offered. Additional factors to be considered as they influence
      primary and secondary endpoints: Assessment of gender and age.

      STATISTICAL METHODOLOGY

      The study is a non-interventional, monocentric cohort study. The scores which will be
      analysed as primary and secondary endpoints are in general not assumed to follow a normal
      distribution. Differences in the raw (untransformed) scores and for changes of the scores
      over time, will be described by descriptive statistics. The hypotheses of the primary and
      secondary endpoints described below, will not be examined by any statistical tests.

      Hypothesis

      The investigators hypothesize that intraoperative pain perception, measured by the NRS, in
      patients with less preoperative fear and anxiety must be lower. The scores listed as
      secondary endpoints are hypothesized not to change between pre- and post-operative
      measurement.

      As the expected sample size is not large enough to carry out a statistical test with adequate
      power, no hypothesis testing will be carried out for this study. The evidence for differences
      in the scores of the primary and secondary endpoints will be discussed based on the
      descriptive statistics.

      Determination of Sample Size

      The primary objective of this study is of descriptive nature, i.e., to assess the conscious
      experience and experience and psychological consequences of awake surgery among the patient
      collective at the Cantonal Hospital St. Gallen (Kantonsspital St. Gallen, KSSG). The number
      of included patients is governed by the duration of the study, which is planned to be one
      year. Within this year it is expected that around 20 patients, recruited at the KSSG, will be
      included in the study.

      Statistical criteria of termination of Trial

      There will be no statistical criteria, which would trigger early termination of this trial,
      as long as the data gathering process is not impaired.

      Planned Analyses

      The following measures will be reported: mean, standard deviation, 95% confidence interval,
      median, 1st and 3rd quartile, minimum, and maximum.

      Further the same descriptive statistics will be reported for patient characteristics on
      continuous scale (e.g. age) and percentages will be reported for categorical variables (e.g.
      gender). The Spearman rank correlation, which is a non-parametric measure for correlations,
      for the same scores measured at different occasions, will be reported for the scores in the
      primary and secondary endpoint.

      Datasets to be analysed, analysis populations

      The analysis population includes all eligible patients which were recruited in the study.
      Patients will be included in the analysis if they have included any of the questionnaires.
      Characteristics of patients which did not meet the inclusion criteria will be reported
      separately. If a patient has a missing value, or missed a follow-up visit, only the observed
      measurements will be included and no data imputation will be applied. This implies that the
      data will be analysed according to the intention to treat principle, which should not be
      problematic as no intervention is planned in this study.

      Essentially no subgroup analyses are planned but under the assumption of equal group sizes, a
      descriptive analysis of the examined scores for subgroups of gender and age will complement
      the analysis.

      Primary Analyses

      Descriptive statistics will be displayed for the NRS score and for the changes in the NRS
      score between the pre-operative and intra-operative and the pre-operative and post-operative
      measurements.

      Secondary Analyses

      For the measures of the secondary analysis (PHQ-D, BDI, MMSE, HADS-D, PDS-1 and BPI)
      descriptive statistics for each measurement occasion and for the changes in the measures will
      be carried out.

      Interim Analyses

      No interim analysis is planned. The duration of the study will be one year. However, interim
      analyses are possible if requested by the investigator, as the data will be analysed with
      descriptive statistics only and no intervention is planned.

      Deviations from the original statistical plan

      Deviations from the planned statistical analysis will be documented and justified in the
      final statistical report.

      Handling of missing data and drop-outs

      Patients who have not submitted any of the questionnaires will be excluded from the analysis.
      However, patient characteristics for patients submitting and not or only partially submitting
      questionnaires will be compared to determine if there are any statistically significant or
      clinically relevant differences between the two groups. This may affect how the results of
      the study should be interpreted.

      DATA AND QUALITY MANAGEMENT

      Data handling and record keeping / archiving

      All data will be recorded in an excel-file, only accessible by authorised personnel, such as
      Werner Surbeck, Hejrati Nader. The questionnaires will be saved by Werner Surbeck in his
      locked bureau during the study. On the Case Report Forms (CRF) and other project specific
      documents, subjects are not identified by their names, but by a unique subject number (UPN).

      Confidentiality, Data Protection

      Project data will be handled with uttermost discretion and is only accessible to authorized
      personnel who require the data to fulfil their duties. On the CRFs and other project specific
      documents, subjects are not identified by their names, but by a unique subject number (UPN).
      UPN will not consist of initials of the subjects or their date of birth.

      The UPN will be distributed to all subjects to whom the questionnaires will be given and used
      from this moment on exclusively. Subject identification list will be compiled and stored by
      Dr W. Surbeck in an Excel sheet only on his personal laptop secured by a strong password. A
      regular backup of the subject identification list will be stored on a Universal Serial Bus
      (USB) device by Dr Surbeck and locked securely in his office. All alterations in the list
      will be done by Dr W. Surbeck exclusively.

      Coding

      On the CRFs and other project specific documents, subjects are not identified by their names,
      but by a unique subject number (UPN).

      Archiving and Destruction

      All trial data, including documents necessary for patient identification and post-trial care,
      will be archived for a minimum of 10 years upon premature- or trial termination.

      ANNNOUNCEMENTS AND REPORTS

      In the event of serious announcements, they will be performed according to Art. 21 (HFV).

      PUBLICATION AND DISSEMINATION POLICY

      Publication of results

      Publication of the study results is planned. An acknowledgement to the Clinical Trials Unit
      (CTU) St. Gallen is enclosed in any publication that will result from this study. The study
      will be registered at clinicaltrials.gov.

      FUNDING AND SUPPORT

      No funding necessary.

      INSURANCE

      In the event of study-related damage or injuries, the public liability insurance of the
      Sponsor (i.e. the Kantonsspital St. Gallen) provides compensation, except for claims that
      arise from wilful misconduct or gross negligence.
    

Intervention name(s): Screening through questionnaires
Intervention type(s): Other
Intervention description(s): Distribution of Questionnaires to every participant within the single existent Arm at three times.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Consecutive ongoing recruitment through investigator(s) in daily clinical practice
        (consultations). The subjects will receive the consent form with an address and phone
        number indicated where further questions regarding the study can be discussed directly with
        the project leader. This will take place at least one week before the hospitalisation.
      
Keywords: Awake craniotomy; Psychological consequences; Fear and Anxiety