An Interactive Advance Care Planning Intervention to Facilitate a Good Death for Cancer Patients
Condition: End Stage Cancer
Study type: Interventional

Summary: 
      The purpose of this 5-year interventional study is to design, implement, and evaluate the
      effectiveness of an intervention aimed at facilitating prognosis communication and
      end-of-life care decision-making to increase the extent of congruence between the patient's
      preferred and actual EOL care received and patients' and family caregivers' QOL and
      psychological well-being, reduce futile aggressive healthcare resources utilization at
      end-of-life, and facilitate bereavement adjustment.
    

Detailed description: 
      A randomized controlled trial with a tailored, multifaceted intervention will be conducted on
      a convenience sample of 231 dyads of terminally ill cancer patients and caregivers with the
      same number of attention controlled group to evaluate the intervention's effectiveness.

      Sample size calculation: There was no interventional study directly investigating the
      effectiveness in increasing the extent of congruence between patient preferred and actual
      end-of-life (EOL) care received by terminally ill cancer patients; therefore sample size
      estimation will be based on the effectiveness of holding EOL care discussions between
      patients and physicians on the extent to increase congruence between the patient's preferred
      and actual EOL care received. Patients who reported having EOL care discussions with their
      physicians significantly more likely to receive EOL care consistent to their preferences
      (OR=2.26; p<.0001) and received significantly fewer aggressive medical interventions near
      death, with lower rates of CPR (0.8% vs 6.7%; AOR, 0.16; 95% CI, 0.03-0.80), mechanical
      ventilation support (1.6% vs 11.0%; AOR, 0.26; 95% CI, 0.08-0.83), and ICU care (4.1% vs
      12.4%; AOR, 0.35; 95% CI, 0.14-0.90), respectively. A sample size of 124-195 dyads per group
      achieves 80% power to detect a difference between the interventional and control group by a
      two-sided hypothesis test with a significance level of 0.05. In compensating the 18.5% of
      attrition rate found in our previous longitudinal study, 147-231 dyads per group are needed.
      The proposed sample size will be targeted on 231 dyads per group to ensure adequate power to
      detect the hypothesized effects of the proposed intervention.

      Approximately 8-10 new dyads of terminally ill cancer patients and their family caregivers
      were recruited in each month. In order to recruit the targeted 462 dyads (231 dyads in each
      treatment group) of subjects, after development of detailed study protocol, subjects will
      start to enter into the study at the beginning of the 6th month of the study through the 54
      th month and be followed through the 5th year of the proposed study period. We will enroll
      and randomly assign eligible dyads of terminally ill cancer patients and their family
      caregivers into intervention or attention controlled group in a 1:1 fashion without
      stratification.

      Data collection procedures: Assessments will be performed prospectively and continue until
      patient death, loss to follow-up, study withdrawal, or when the patient can no longer be
      interviewed. An every-3-week time frame will be used in this study for repeated QOL and other
      outcomes assessments for both patients and their family caregivers bases on the review of
      literature to cover the most rapid change of patient physical conditions and demanding period
      of caregiving until the death of the patient. After each patient's death, a chart review and
      postmortem interview with patients' caregivers will be performed to confirm the type of
      medical care received at the EOL. Bereavement interviews will be conducted 1, 3, 6 and 13
      months after the time of death in order to avoid contamination on the basis of anniversary
      grief reactions.1

      Several strategies will be taken to ensure research fidelity.

        1. The proposed intervention requires professionals skilled in the content, techniques, and
           delivery of the intervention. Built on her previous oncology and hospice care
           experiences, a competency-based educational approach will be used to train the
           facilitator. The training will include an overview of the study protocol and procedures,
           a review of the developed workbook and video, and instructions in motivational
           assessments. The principal investigator (PI) will serve as a role model for the
           facilitator to coach her how to assess and motivate participants at different stage of
           the readiness for engagement in ACP and cooperate with physicians in coordinating and
           facilitating EOL care discussions. The facilitator needs to successfully demonstrate
           predefined competencies and consistency to delivery of the ACP intervention after
           training and receipt of individual feedback from the PI before formal interventions can
           be conducted. Thereafter the study team will meet biweekly to review the facilitator's
           notes on interventional sessions and to provide feedback on difficult subject management
           issues.

        2. Interventions provided to subjects assigned to the intervention group will be compared
           with those received by those who assigned to the control group every 3 months. Randomly
           selected dyads of terminally ill cancer patients and their family caregivers in each
           treatment group will be interviewed by the PI to check the extent to which treatments
           provided to them consistent with the protocol for each group.

        3. To avoid bias, separate data collectors will be hired and trained for the study to
           collect data for the intervention and the control group independently. Training will
           include screening subjects, obtaining consents, and administering the project
           instruments without offering information; research assistants (RAs) will be blinded to
           treatment conditions. Procedures will be implemented to insure the standardization of
           data collection. RAs reliability will be established by comparing data collected by the
           RAs with that recorded by the PI on five pilot cases. Ninety-five percent agreements
           will be required before data collection for main study can begin. Failure to reach this
           agreement rate will require additional training until the acceptable reliability level
           is reached. Intermittent reliability checks will be carried out by the PI throughout the
           study to maintain a 95% agreement.

        4. An independent Data and Safety Monitoring Board (DSMB) will be organized to ensure
           continuing patient safety as well as the validity and scientific merits of the trial.
           The DSMB will constitute a biostatistician experienced in statistical methods for
           clinical trials, a nursing researcher experienced in conducting RCTs, and a
           physician-scientist experienced in cancer care.

      The DSMB will monitor and address the following issues: (1) sufficient and appropriate
      enrollment of subjects, including compliance with the eligibility criteria for each dyad of
      terminally ill cancer patients and family caregivers enrolled in the trial, (2) appropriate
      implementation of randomization, (3) comparability of baseline data between treatment groups,
      (4) protocol compliance, including treatments delivered to each treatment group and the data
      collection schemes,(5) adverse events (AEs), quality assurance for data validation and
      registry procedures for Clinical Trial registration at ClinicalTrials.gov.

      A databet that records number of recruitment each month and the baseline information will be
      maintained to ensure sufficient and appropriate enrollment of subjects.

      A dataset that captures the values the personnel used to randomize participants will be
      maintained, thereby allowing the process of treatment allocation to be reproduced and
      verified later. The DSMB will monitor the appropriate implementation of randomization by
      reviewing this dataset.

      Interventions delivered to subjects assigned to the intervention and the attention-controlled
      group will be compared every 6 months by interviewing randomly selected dyads of terminally
      ill cancer patients and their family caregivers in each treatment group to check treatments
      provided to them.

      AEs will be recorded and submitted by the study team in written to the DSMB monthly, with
      immediate reporting of serious AEs to the DSMB and an oncologist with expertise in cancer
      care. Site reports AEs/SAEs to its IRB will be dictated by local requirements.

      No data will be analyzed before the study ended. Access to interim results, including results
      according to study arm will be limited to the DSMB members and the statistician who prepared
      the reports only. The DSMB will review study data every 6 months and the DSMB' summary
      recommendations will be directed to the PI. A summary of the review of reported AEs/SAEs will
      be sent to the local IRB to ensure that the participating center will be informed of any
      pertinent safety issues.

      The biostatistician will be responsible for ensuring quality of data submitted to the
      registry against the predefined range of each independent and dependent variable and
      assessing the accuracy and completeness of registry data by comparing the submitted data to
      the original data.

      Data analysis and interpretation:

        1. All data will be scored and entered into a computer spreadsheet by an administrative
           assistant blinded to the group allocation of the participant.

        2. In order to test for baseline group equivalence, differences between study groups in
           baseline characteristics and identified outcomes will be assessed with the use of
           two-sided Fisher's exact tests and chi-square tests for categorical variables and
           independent-samples Student's t-tests for continuous variables.

        3. Intention-to-treat regression analyses will be performed with generalized estimating
           equations (GEE) to examine the effectiveness of intervention. In the intention- to-treat
           regression analyses, all participants will be analysed in the treatment group to which
           they are initially allocated regardless of whether they complete or withdraw from the
           treatment until the patient dies.

        4. The extend of congruence of the terminally ill cancer patients' preferred and actual EOL
           care received will be obtained by comparing the agreement between the preferences of EOL
           care elicited at the last assessment and actual EOL care received by the patient by the
           percentage of overall agreement and kappa coefficients to assess the extent of
           congruence to correct for the amount of agreement that can be expected to occur by
           chance alone.

        5. Multivariate logistic regression by the GEE will be used to examine the impact of
           intervention on improving the extend of congruence between terminally ill cancer
           patients' preferred and actual EOL care received, and secondary outcomes, namely
           increasing prognosis awareness, EOL care discussion, and the extent of patient-family
           agreement on preferences of EOL care, decreasing use of futile aggressive EOL care, and
           facilitating hospice use and early hospice referral, with simultaneously adjusting for
           confounding factors. The moderation effects of prognosis awareness, EOL care discussion,
           and patient-family agreement on preferences of EOL care on extend of congruence between
           terminally ill cancer patients' preferred and actual EOL care received, decreasing use
           of futile aggressive EOL care, and facilitating hospice use and early hospice referral
           between interventional group and the attention controlled group also will be examined in
           the GEE model.

      7. Multivariate multiple regression by the GEE will be used to test the effectiveness of
      intervention in improving patients' and family caregivers' QOL and psychological well-being
      (anxiety and depression), and family bereavement outcomes (including QOL, depression, and
      grief reactions), with simultaneously adjusting for confounding factors. The moderation
      effects of prognosis awareness, EOL care discussion, and patient-family agreement on
      preferences of EOL care on the differences in patients' and family caregivers' QOL and
      psychological well-being before the patient's death, and family bereavement outcomes between
      intervention group and the attention controlled group also will be examined in the GEE model.
      How limiting futile aggressive EOL care and the extent of congruence between terminally ill
      cancer patients' preferred and actual EOL care received will moderate the intervention's
      effectiveness on improving patients' and family caregivers' QOL and psychological well-being
      before the patient's death and family bereavement outcomes also will be examined in the GEE
      model.
    

Intervention name(s): Interactive advance care planning; Attention usual care
Intervention type(s): Behavioral; Behavioral
Intervention description(s): The facilitator will begin each course of intervention by assessing the patient's and his/her family caregiver's readiness for engagement in ACP independently.
Providing participant-centered care tailored to the specific needs of participants at each stage of readiness for engagement in ACP.
Facilitating EOL care discussions throughout the dying process.
A workbook and a video decision aid that briefly describes ACP to enhance participants' understanding of the essential elements in ACP.; a consistent master prepared nurse on the study team will provide the attention portion of the care. The initial meeting will occur before the patient discharges from hospital and the usual care nurse will give patients and family caregivers a workbook and a video with educational materials on how to manage common symptoms and a comprehensive list of resources available, including patient support organizations, support and financial assistance through the social work department..
Other intervention name(s): Interactive ACP
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: End-of-life care; Preference of end-of-life care; RCT; Terminally ill cancer patients