The PediQUEST Study: Evaluation of Pediatric Quality of Life and Evaluation of Symptoms Technology
Condition: Pediatric Neoplasm; Quality of Life; Outcome Assessment; Palliative Care
Study type: Interventional

Summary: 
      Over 50% of children dying from cancer still suffer from symptoms that could be effectively
      alleviated. The purpose of the Pediatric Quality of Life and Evaluation of Symptoms
      Technology (PediQUEST) Study was to evaluate whether providing feedback to families and
      providers about how the child is feeling improved child distress and quality of life (QoL) in
      children with advanced cancer.

      PediQUEST is a computerized survey that asks the child and/or parents how the child has been
      feeling, i.e. whether the child had any physical or emotional symptoms, as well as how other
      aspects of life, such as school and friends, are going. After the survey is complete a report
      that summarizes patient/parent answers is printed. When a child reports moderate to high
      distress from any symptom an email is automatically sent to the primary providers
      (oncologist, nurse, and psycho-social clinician as well as the pain and palliative care
      services) alerting them about the child's distress.

      In this study we evaluated whether using PediQUEST and providing printed reports to parents
      and providers reduced distress and improved quality of life in children with advanced cancer.
      In addition, we wanted to understand whether it was feasible to carry out a randomized
      controlled trial in children with advanced cancer. Finally, the data collected, will be used
      to describe the natural history of symptoms and quality of life as reported by the children.

      Children enrolled in the study (or their parents) were asked to complete a PediQUEST survey
      at most once a week. A random half of the children received the feedback intervention, i.e.
      patients, parents, and providers received printed reports (and emails if the child was in
      distress). The other half only completed the PediQUEST surveys and did not receive reports.
      We analyzed data collected over 20 weeks of follow-up to see whether receiving PediQUEST
      reports had any effect on child distress and quality of life.
    

Detailed description: 
      Introduction: Cancer is the leading cause of nonaccidental death in childhood.(Arias et al.
      2003) In spite of significant scientific progress, one quarter of children with cancer still
      do not survive(Greenlee et al. 2000), and over 50% experience substantial suffering that
      could be alleviated.(Wolfe et al. 2000a) Pediatric palliative care is now an expected
      standard of care and research in this field has been established as a national priority by
      the Institute of Medicine (IOM).(Field et al. 2003) Earlier work by our group suggested that
      when parents and physicians recognized at an early stage that a child had no realistic chance
      of cure, they were more likely to integrate elements of effective palliation into the child's
      care. However, this early stage concordance about prognosis was rare.(Wolfe et al. 2000b)
      Communication and delivery of optimal care in the advanced stages of illness is especially
      challenging in children.(Shelton 1999) The anticipation of losing a child and physicians' own
      difficulties(Saunders 1979-80; Hilden et al. 2001) may hinder discussions about poor
      prognosis and impact on decision-making and integration of palliative care. Thus attention to
      symptom management and quality of life (QoL) in children with advanced cancer may be limited.

      The collection of standardized symptom and QoL data has shown to enhance physician's
      recognition, knowledge and accuracy in the assessment and palliation of symptoms, and to
      increase patient-provider discussions about QoL issues and directly improve patient's
      QoL.(Detmar et al. 2002; Taenzer et al. 2000; Velikova et al. 2004) Whether these findings
      are applicable to children remains to be established.

      One of the obstacles to routine symptom and QoL assessment in children is the need of
      developmentally adapted(Eiser et al. 2001b; Eiser et al. 2001c; Hain 1997) and parent-proxy
      tools(Eiser et al. 2001a), making the paper and pencil format extremely impractical.
      Computerized surveys offered a potential solution. Patient acceptance of such devices has
      been found to be high.(Buxton et al. 1998; Velikova et al. 2002; Velikova et al. 1999;
      Velikova et al. 2001) Our current project -the PediQUEST Study- consists of a pilot for a
      randomized controlled trial (RCT) aimed at assessing the effect of routinely reporting
      symptom and QoL data. We will use an innovative data collection strategy: a hand-held
      computer devise, the Pediatric Quality of Life and Evaluation of Symptoms Technology
      (PediQUEST) that readily administers a user-appropriate survey instrument and generates
      reports summarizing how the patient feels.

      As far as we are aware of, this will be the first RCT conducted in children with advanced
      cancer to evaluate a palliative care intervention. Given the challenges with doing research
      in this population, we propose to simultaneously focus on several goals.

      Aims: Aim 1: (Feasibility study) Assess the feasibility of conducting a randomized controlled
      supportive care trial (RCT) in children with advanced cancer. Aim 2: (PediQUEST Evaluation)
      Preliminarily assess the effect of routinely feeding back QoL and symptom data to families
      and primary oncologists, and alerting supportive care teams about highly distressing
      symptoms. Aim 3: (Descriptive study) Prospectively explore determinants of child's suffering
      and parental-physician discordance regarding prognosis and treatment goals in children with
      advanced cancer.

      Design: Aim 1: Cohort survey study; Aim 2: Pilot prospective RCT; Aim 3: Cohort study
      embedded in an RCT.

      Setting: Three large US pediatric cancer centers. Subjects: 104 children 2-years old and
      above with advanced cancer and their parents were enrolled between December 2004 and June
      2009.

      Follow-up: Patients were initially followed up for 9 months or until death whatever occurred
      first. However, an interim analysis of the first 29 patients showed that 75% were alive at
      nine months, suggesting the enrollment of a healthier cohort. We therefore changed the
      follow-up period to 3 months with the option of multiple re-enrollments until the end of data
      collection (December 2009) or death.

      Methods:

      Feasibility study: All subjects approached for enrollment were invited to complete a one-time
      paper and pencil "Consent survey" regardless of their decision about whether to participate.
      All enrolled subjects were asked to complete a paper and pencil "Participation survey" after
      completing the study or dropping-out in order to explore determinants of attrition.

      PediQUEST Evaluation and Descriptive studies: Symptom and QOL scores were tracked up to once
      a week. Surveys were embedded in the PediQUEST system and administered through tablet
      computers.

      Participants' recruitment: Eligible children were identified through daily review of clinic
      roster with clinic staff including nurses, oncologists and/or nurse practitioners and
      verified with the patient's primary oncologist using a checklist sent over email. If after
      being introduced to the study and having had the opportunity to ask questions, child and
      parent(s) were willing to participate, parent(s) were asked to review and sign the informed
      permission/assent document covering the parent(s) and child's participation. A provider's
      completion of the eligibility checklist will indicate informed consent of providers.

      Study Instruments:

        1. PediQUEST survey (PQ-Survey): assessed symptoms, quality of life, and overall sickness.
           Nine survey versions were developed to allow for consistent measurement across the age
           ranges and respondents. Self-report started at 5 years of age; children aged 5 to 12
           years answered shorter, age-adapted questionnaires which were complemented with
           additional parental questionnaires; teens answered a full self-report questionnaire.
           Parents of children between 2 and 4 years old answered a full survey on their child's
           behalf. If a child did not feel well, parents could complete the full questionnaire on
           their behalf. PQ-Surveys were pilot tested in 15 patients showing good acceptability and
           comprehensibility. PQ-surveys used four tools: 1) PQ-Memorial Symptom Assessment Scale
           (MSAS), adapted from previously validated child(Collins et al. 2000; Collins et al.
           2002) and proxy(Drake et al. 2003) MSAS, measures frequency, severity and distress for
           24 symptoms; 2) Pediatric Quality of Life Inventory (PedsQL), a 22-item health related
           quality of life instrument;(Seid et al. 1999; Varni et al. 2002; Varni et al. 2003) 3)
           Faces Pain Scale Revised (a faces pain scale, used to measure current pain
           intensity);(Hicks et al. 2001) 4) Sickness VAS scale (overall sickness measure created
           ad hoc).

        2. Survey about Caring for Children with Cancer (SCCC): In addition, parent and physician
           perspectives regarding prognosis and treatment goals were collected at baseline and then
           every 3 months using a paper-and-pencil survey SCCC, adapted from our survey for
           bereaved parents.(Wolfe et al. 2000b)

        3. Post death survey: If patients died within the study period parents were invited to
           complete a post-death survey at least four months following the death to assess distress
           during the last month of life and retrospective perspectives regarding the overall
           quality of care.

        4. Satisfaction Surveys: Child and parent surveys were adapted from existing
           questionnaires.(Grogan et al. 1995; McCusker 1984; Weaver et al. 1993) Satisfaction with
           PQ technology was assessed using seven items for children eight years old and above and
           11 items for parents. Surveys were embedded in the PediQUEST system and administered at
           fourth and eighth PediQUEST administration. A survey evaluating participant's
           satisfaction with the PediQUEST intervention (see below) was administered concurrently
           (eight items (parents), five items (children eight years old and above)) to all
           intervention participants. Provider satisfaction with the PQ intervention, and perceived
           usefulness of the PQ-system was assessed through an online survey administered at the
           end of data collection.

      Intervention: Patients were randomly allocated to receive routine feedback about symptoms and
      QOL. The feedback intervention had two components: (i) PQ-reports: printed reports were made
      available to providers (inserted in charts before the visit) and families (handed immediately
      after survey completion at clinic or ward). PQ-reports consisted of bar plots of PedsQL and
      MSAS symptom scores from current and four prior administrations, a summary highlighting
      changes since last report, and a list of available resources for symptom control (for
      families), or generic pain management recommendations (for providers). Training on how to
      interpret PQ-reports was offered to families at enrollment and on an annual basis to
      providers; (ii) PQ emails: were automatically generated if PQ-MSAS individual symptom scores
      were ≥70, or if on two consecutive administrations the patient or parent reported a score of
      ≥70 for any frequency, severity or distress item, or a PedsQL total score ≤ 40. E-mails were
      sent to primary providers (oncologist, nurse, and psychosocial clinician), the local
      palliative care service, and, when pain was reported, the pain service (or equivalent). No
      instructions were imparted on how to respond to emails. Families and providers of patients in
      the control arm of the study did not receive feedback reports. The allocation process was
      embedded in PediQUEST and blinded to investigators until the patient completed the first
      survey. Because of the nature of the intervention this was an open label study. As a token of
      our appreciation, small non-monetary incentives were provided to children, parents, and
      providers.

      Outcomes: This study explores the feasibility of conducting an RCT assessing a supportive
      care intervention in children with advanced cancer (aim 1). It also provides estimates of
      consent and attrition rates, its determinants, and the burden associated with repeated
      measurements. In addition, this pilot study will preliminarily assess the impact of feedback
      on child's distress and quality of life. Main outcomes of this efficacy study (aim 2) are
      presented below. This pilot study will render sufficient data for accurate sample size
      calculation for future studies and serve to explore determinants of suffering in children
      with advanced cancer (aim 3).

      Statistical Analysis:

      PediQUEST Evaluation (Aim 2): To assess the effect of PediQUEST, the proportion of patients
      with unrelieved symptoms in each arm will be compared using odds ratios and associated
      chi-square tests. To assess the progression of reported levels of child's distress and QOL
      trends, we will run a mixed effects model that assumes a linear trend in the outcome over 20
      weeks of follow up for each subject. The model will examine the difference in the average
      trend over time (slope) between the intervention and control group by including a fixed
      effect term that represents the interaction of treatment status and time since study entry.
      Lack of difference between slope coefficients will support the null hypothesis of no effect
      by the intervention. Single point secondary outcomes will be analyzed by comparing both arms
      with a t test or Wilcoxon rank-sum test for continuous outcomes and odds ratios and
      associated chi-square tests for proportions.

      Sample Size and Power Calculations A formal sample size estimation was not possible given the
      lack of data on distribution of scores in an advanced cancer population or their variation
      over time. For this reason we originally proposed to recruit 120 patients and their parents,
      a sample size driven by practical rather than statistical considerations that would serve as
      a basis for future sample size calculations. We estimated that 60 subjects per arm would
      allow for an adequate balance between arms and likely provide sufficient power to detect
      large clinical effects for single point measurements.
    

Intervention name(s): Routine Data collection; Feedback of patient-reported outcomes
Intervention type(s): Other; Other
Intervention description(s): Patients assigned to the control arm answered PediQUEST (PQ) surveys at most once a week and at least once a month. PQ-surveys were administered through a tablet computer if patient was at the clinic or ward or over the phone if patient was primarily at home. PQ-survey had 9 age- and respondent- adapted versions.
Control arm participants reported their satisfaction with the PediQUEST technology twice 4th and 8th PediQUEST administration. These surveys were embedded in PediQUEST.; Patients, parents and primary providers received printed reports summarizing patient/parent reported outcomes for last five visits. When child reported moderate-severe distress an email was automatically sent to primary providers (oncologist, nurses and psychosocial clinicians), as well as to the pain and palliative care services.
Other intervention name(s): Control arm; Feedback; Intervention arm
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Pediatric Advanced Cancer; Children; Quality of Life; Health Information technology; Patient reported outcomes