SEARCH

SEARCH BY CITATION

Keywords:

  • disease-related;
  • kidney cancer;
  • renal cell cancer;
  • signs and symptoms

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

Objectives:  Using patient and expert provider input, we previously developed a 15-item index of the most important symptoms and concerns of people being treated for advanced kidney cancer, the Functional Assessment of Cancer Therapy—Kidney Symptom Index (FKSI). These 15 concerns are a mixture of disease-related symptoms and treatment-related side effects. As a result, it may be difficult to assign an informative label to the score defined as the summation of these 15 most important concerns. Because one of the primary goals of treating advanced kidney cancer is the relief of disease-related symptoms, we set out to differentiate from the list of 15 symptoms those that are predominantly attributable to kidney cancer itself rather than its treatment, and to evaluate this abbreviated FKSI—Disease-Related Symptoms (FKSI-DRS).

Methods:  Survey results from 18 experienced clinical experts were summarized to separate DRS from other concerns more arguably attributable to treatment side effects. This nine-item FKSI-DRS was then validated on a sample of 141 people with kidney cancer.

Results:  The FKSI-DRS is reliable (internal consistency range = 0.75–0.78; test–retest reliability intraclass correlation = 0.85), and valid, separating groups by performance status and the patient's own global rating of change. The likely minimally important difference in the FKSI-DRS is in the range of 2–3 points.

Conclusions:  The FKSI-DRS is a reliable, valid, and responsive brief index of the most important symptoms associated with advanced kidney cancer.


Introduction

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

Patients with many types of advanced cancer, including kidney cancer, face a reduced life expectancy and no cure for their disease, making relief of physical symptoms and maintenance of function the primary objectives of medical intervention [1–3]. This highlights the need for a symptom index that can provide a clinically appropriate and precise evaluation of symptomatology and increased sensitivity to the impact of drug therapy. The availability of such an instrument would allow for the assessment of symptom benefit, a potentially important end point in clinical trial evaluations. Such indexes may also be valuable when monitoring treatment adherence, an increasingly important issue with the expansion of oncology into oral chemotherapy.

Disease-specific symptom assessment has potential to play a key role in evaluating patient-related end points in clinical trials. The use of global quality of life scores may obscure important and significant changes in disease-related symptoms when those symptoms are embedded in a larger instrument [4], which underscores the importance of targeting assessment toward prespecified, priority disease-related symptoms. Furthermore, a scale comprised of symptoms that clinicians have determined to be disease-related could function in support of a new drug approval for indication or label claim regarding benefit to disease-related symptoms.

We previously used patient and physician input to develop and validate a 15-item scale to assess the most important targeted symptoms and concerns related to evaluating treatment effectiveness in advanced kidney cancer, the Functional Assessment of Cancer Therapy—Kidney Symptom Index-15 (FKSI-15) [5]. The FKSI-15 demonstrated good internal consistency, convergent validity, successful differentiation of patients known to differ in clinical status, andresponsiveness to change in clinical status over time. We also computed a minimally important difference (MID) range of 3–5 points for the FKSI-15.

In regulatory review of the FKSI-15 and similar scales, concern is often raised about the fidelity of the questions asked with regard to the label claim being sought. For example, if one seeks to evaluate symptoms of disease that are important to patients, one must ensure that those symptoms being measured are not merely important, but also likely to be caused by the disease process being treated. We therefore initiated a project to differentiate disease-related from treatment-related symptoms in this scale using input primarily from clinical experts and secondarily from kidney cancer patients, which resulted in the FKSI—Disease-Related Symptoms (FKSI-DRS). The objective was therefore to derive a brief index of disease-related symptoms from the longer list of symptoms known to be important to patients. Because the FKSI-DRS is comprised of a subset of items from the FKSI-15, we used patient data from the FKSI-15 validation study to validate the FKSI-DRS.

Methods

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

Participants

Physician sample: FKSI-DRS development and validation.  Experts who treat kidney cancer were selected as the appropriate group to help differentiate disease-related symptoms and concerns from treatment-related or other concerns. Although patients unquestionably are expert at identifying what is most important or valued to them, they are not objective evaluators of the extent to which a symptom or problem is disease- versus treatment-related. It is common (and arguably an adaptive coping mechanism) for patients to interpret their disease symptoms as caused by treatment or other nonthreatening factors. Thus, asking experienced physicians who are more objective about the attribution of cause to a given priority symptom seems necessary. After receiving approval from the institutional review board, we identified 37 eligible experts who were in national clinical cooperative groups, recognized key opinion leaders (based on publications and presentations over the past 3 years), and medical advisors to the Kidney Cancer Association (KCA); email addresses were located for 35 of these experts. A second reminder e-mail resulted in overall participation within a 10-day follow-up period of 18 physicians (51.4%). We also distributed the survey to a group of 13 physician experts in kidney cancer who were participating in an industry-sponsored kidney cancer investigator meeting, for a total of 31 experts.

Sociodemographic information was collected on the sample of 18 physicians but not on the remaining 13 (see Table 1). Of the 18 experts, the mean age was 47.7 (SD = 9.4) years and 89% were male. The mean number of years in practice was 16.1 (SD = 7.8) and ranged from 4 to 29 years. Physicians indicated their medical specialty as either medical oncology (n = 15, 83%) or surgical urologic oncology (n = 3, 17%). Over a third of the physicians (n = 6, 33%) reported experience treating over 1000 patients with kidney cancer, with over half of the sample of 18 (n = 11) experienced at treating 200–999 patients.

Table 1.  Description of patient and physician samples
 FrequencyPercent
  1. ECOG, Eastern Cooperative Oncology Group.

Partial physician sample (n = 18)
 Age (years)
  Mean (SD)  47.67 (9.4)  
  Range  34–62  
 Sex
  Male1688.9
  Female211.1
 Number of patients treated
  <20015.6
  200–499422.2
  500–999738.9
  1000+633.35
Patient sample (n = 141)
 Age (years)
  Mean (SD)  59.57 (9.8)  
  Range  37–82  
 Sex
  Male9567.4
  Female4632.6
 Race/ethnicity (includes reports of multiple ethnicities)
  White139 
  African American1 
  Asian0 
  American Indian/Alaskan native2 
 Patient-rated ECOG performance status
  Normal activity, without symptoms6546.4
  Some symptoms, no bed rest5035.7
  Some amount of bed rest2517.9
 Prior chemotherapy
  No9164.5
  Yes5035.5
 Prior radiation therapy
  No9668.1
  Yes4531.9
 Currently receiving therapy
  No9366.0
  Yes4834.0

Patient sample: FKSI-DRS validation.  Patient data from the FKSI-15 validation study was used for analyses of the FKSI-DRS. Patients were constituents of a national patient support and advocacy organization, the KCA, who responded to information about the study provided at a national conference, by postal mailing, electronic mailing, or the KCA monthly electronic newsletter. Of 318 patients inquiring about the study, 157 patients were eligible and were mailed a consent form to be signed and returned along with study materials. Interviews were scheduled with 143 patients; 14 were not enrolled because of: illness or death (n = 2), declined participation (n = 6), failure to return consent forms (n = 4), or invalid consent forms (n = 2). One hundred forty-one patients with kidney cancer ultimately participated in the validation phase of this study (one patient who had consented died, one could not be reached). There was good compliance with the study assessments: 100% at time 1, 96% at time 2 and 93% at time 3. Twelve patients went off-study because of: death (n = 4), inability to contact (n = 6), illness (n = 1), and administrative error (n = 1). Complete data from all three assessments were available from 126 patients (89% of sample). A convenience sample of 15 of these patients also participated in a semistructured interview to obtain additional patient input about priority kidney cancer symptoms.

The sociodemographic characteristics of the patients are also summarized in Table 1. Participants had a mean age of 60 (SD = 9.8) years, were mostly male (67%) and predominately White (99%). Eighty-two percent had an Eastern Cooperative Oncology Group Performance Status Rating (ECOG PSR) of 0–1 at baseline, with a majority reporting a history of treatment with chemotherapy (65%) or radiation therapy (68%) and most currently receiving treatment (66%).

Measures

FKSI-DRS development.  We constructed a survey to enable expert physicians to indicate on a per-item basis whether each of the FKSI-15 items was exclusively disease-related, predominantly disease-related, too close to determine, predominantly treatment-related, exclusively treatment-related, or neither disease- nor treatment-related (see Table 2). Respondents were asked to indicate one of the six possible response options for each symptom/concern. In addition, the first 18 respondents were asked to provide descriptive information including age, sex, medical specialty, years in practice, and estimated total number of kidney cancer patients treated. We used a predefined scoring system to tabulate results. Ratings of “exclusively disease-related” or “exclusively treatment-related” were given more weight (±2 points) than those rated “predominantly disease-related” or “predominantly treatment-related” (±1 point). Ratings of “too close to determine” were assigned a score of “0.”

Table 2.  Frequency of physician responses to FKSI items: disease- versus treatment-related
 Exclusively disease-relatedPredominantly disease-relatedToo close to determinePredominantly treatment-relatedExclusively treatment-relatedNeither
  1. FKSI, Functional Assessment of Cancer Therapy—Kidney Symptom Index.

I have a lack of energy1818301
I am bothered by side effects of treatment00415120
I have pain12180001
I am losing weight21512001
I have bone pain17111001
I feel fatigued1818200
I am able to enjoy life02133011
I have been short of breath4176001
I worry that my condition will get worse15104001
I have a good appetite03113012
I have been coughing9172001
I am bothered by fevers41114001
I am able to work (include work at home)01152110
I have had blood in my urine17101002
I am sleeping well02143011

FKSI-DRS validation.  Patients participating in the validation of the FKSI-15 (and FKSI-DRS) completed the Functional Assessment of Cancer Therapy—General (FACT-G) [6], the ECOG PSR [7], and the Global Rating of Change Scale (GRCS; adapted from Jaeschke et al. [8]).

The FACT-G is a multidimensional health-related quality of life (HRQL) instrument with established reliability, validity and responsiveness to change [6]. The FACT-G contains 27 items divided among four general subscales: Physical Well-Being (PWB), Social/family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB) using a five-point Likert-type scale ranging from 0 (“not at all”) to 4 (“very much”). Scores are obtained for each of the specific domains as well as a total HRQL score.

The ECOG PSR [7] is a single-item rating of the degree to which patients are able to participate in typical activities without the need for rest. The PSR ranges from 0 (“normal activity without symptoms”) to 4 (“unable to get out of bed”). In this study, the PSR was obtained from patients themselves and served as ameans of classifying patients for known-group comparisons.

The GRCS [8] is a series of questions that ask patients to rate the change in their health status over a specified period of time. Questions about perceptions of change in health status are specific to the domains of interest (e.g., PWB, FWB). For each domain, patients specify whether they are worse, about the same, or better. If worse or better, patients then quantify the magnitude of the recognized change using a rating scale ranging from +7 (very great deal better) to −7 (very great deal worse).

Procedure

FKSI-DRS development.  The surveys were distributed to the expert clinicians via email (n = 18) and paper-and-pencil (n = 13). Data were analyzed using two methods. We first examined the distribution of physicians who endorsed each response category for each of the FKSI-15 items. We then examined the means and 95% confidence intervals (CIs) for each of the 15 FKSI items.

A convenience sample of 15 patients from the FKSI-15 validation sample was interviewed and queried about the initial list of 18 potential FKSI-DRS items, and their responses were qualitatively summarized.

FKSI-DRS validation.  The validation study used a pre-post design to assess a patient's experience of symptoms and concerns associated with advanced kidney cancer. Patients were assessed at three time points: enrollment (baseline, or time 1), 3–7 days post baseline (time 2), and 2–3 months post baseline (time 3). The FKSI-DRS is a subsample of items from the FKSI-15. Data on the items comprising the FKSI-DRS were extracted from the FKSI-15 validation data set and analyzed to evaluate the validity of the FKSI-DRS.

Upon receipt of the signed consent form by the research assistant, the patient completed the time 1 questionnaire battery via computer-assisted telephone interview (CATI). A small number of patients attending the national conference were enrolled and completed the first assessment in-person at the conference. Although these two modes of administration might produce different responses, available evidence suggests essential comparability of in-person versus telephone interview [9]. Three to 7 days after the baseline assessment, all patients completed only the FKSI-15 by CATI (time 2). To examine the FKSI-15's responsiveness to change over time, patients completed the same battery of questionnaires 2–3 months after the baseline administration (time 3) by CATI.

Analysis plan.  The FKSI-DRS was analyzed for internal consistency, test–retest reliability, convergent and discriminant validity, and responsiveness to change in clinical status. In addition, we estimated MIDs, which have been defined as the smallest score difference on a HRQL questionnaire that is clinically significant and therefore likely to be meaningful to both patients and clinicians [8,10,11].

Internal consistency analyses were performed at each assessment for the FKSI-DRS using Cronbach's alpha coefficients. Test–retest reliability was evaluated by calculating an intraclass correlation (ICC) for the FKSI-DRS at baseline and time 2 (3–7 days post baseline). Cross-sectional analyses were conducted to determine the ability of the FKSI-DRS to differentiate definable (“known”) groups according to ECOG PSR. Analysis of variance (ANOVA) techniques were used to compare mean FKSI-DRS scores between ECOG PSR categories. Effect sizes were calculated for group comparisons to provide an indication of the clinical significance of group differences. The associations between FKSI-DRS, FACT-G and subscale scores were evaluated using correlational techniques. To examine responsiveness to change, longitudinal data were used to calculate FKSI-DRS change scores (baseline to time 3) for each patient. Patients were categorized as “worse,”“same,” or “better” according to the global rating of change scale. ANOVA techniques were used to compare mean change scores on the FKSI-DRS between categories of change in the anchor variable (GRCS). As previously described [5], both distribution- and anchor-based methods were used to identify MIDs for the FKSI-DRS.

Results

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

FKSI-DRS Development

Physician ratings of the extent to which 15 FKSI items were believed to be treatment- or disease-related were examined for missing data. Less than 1% of the total expected physician responses to the survey were missing. Any responses of “neither” (54 of 465, 11.6% of total) were excluded from the analyses. Table 2 and Figure 1 summarize the physician ratings of the degree to which items are disease- versus treatment-related.

image

Figure 1. Expert ratings of disease- versus treatment-related attribution by symptom: Means and 95% confidence intervals per FKSI Item. Items rated by experts as “exclusively disease-related” received a score if (+2); “exclusively treatment-related” (−2); “predominantly disease-related” (+1), “predominantly treatment-related” (−1), and ratings of “too close to determine” were assigned a score of 0. FKSI, Functional Assessment of Cancer Therapy—Kidney Symptom Index.

Download figure to PowerPoint

Using the first method of analyses, we identified seven items that were categorized as either exclusively disease-related (i.e., +2) or predominantly disease-related (i.e., +1) by more than 50% of all respondents (i.e., at least 16 of 31). These items assessed pain, weight loss, bone pain, dyspnea (“shortness of breath”), worry, cough, and hematuria (“blood in urine”). Seven other items, although not clearly rated by the majority as disease-related, were quite frequently rated as “too close to determine.” This list included lack of energy, fatigue, ability to enjoy life, appetite, bothered by fevers, ability to work, and sleep. Only the item “I am bothered by side effects oftreatment” was clearly rated as predominantly treatment-related.

Using the second method of analyses, we identified nine items whose 95% CI did not fall below zero (i.e., representative of the “too close to determine” category). These items included all seven items identified as more disease-related by the first method of analyses, plus fever and fatigue. “Lack of energy” came close to significance, with the 95% CI touching zero. This process produced a candidate set of 10 questions from the FKSI for consideration as likely candidates for designation as FKSI-DRS: lack of energy (borderline), pain, weight loss, bone pain, fatigue, shortness of breath, worry that condition will get worse, coughing, bothered by fevers, and blood in urine. Of this list of 10 items, nine are physical symptoms. One is psychological (“I worry that my condition will get worse”), and not likely to be caused directly by disease activity in any physical sense. On the basis that it was highly unlikely that worry as a symptom could be directly attributed as a symptom of kidney cancer, it was deleted from further consideration in the FKSI-DRS, resulting in a nine-item scale (see Appendix I).

Because the reduction of the FKSI-15 to the nine-item FKSI-DRS was based primarily on expert clinical input, we obtained additional patient input during the course of the FKSI-15 validation study. Specifically, we interviewed 15 people with advanced kidney cancer and asked them to respond to eight items that were rated most associated with disease rather than treatment, based on interim results of the expert survey study (n = 18): pain, weight loss, bone pain, shortness of breath, worry that condition will get worse, coughing, bothered by fevers, and blood in the urine. Patients were asked five questions: 1) whether the list of eight expert-derived symptoms represented the most important set of symptoms relative to their condition; 2) the relative importance of fatigue, sleep, and appetite (which were missing from the short list); 3) whether they had experienced significant fatigue since their diagnosis, and if so, whether they thought their fatigue was more physical or mental, and what percentages they would assign to these attributions; 4) whether they thought “fatigue” was different from “lack of energy”; and 5) whether there were any other symptoms they felt were associated with their condition that we should be asking about.

In response to the first question, a majority of the 15 patients (n = 10, 67%) endorsed the list of items as the most important symptoms relative to advanced kidney cancer. Patients volunteered symptoms that were not on the list, including fatigue/lack of energy (n = 3), reaction of loved ones/concern about family relationships (n = 3), and depression/worry (n = 1). Responses to the second question revealed clear endorsement of fatigue (n = 11) from patients and mixed endorsement of appetite (n = 7) and sleep (n = 6) as problems associated with advanced kidney cancer. Consistent with the prior question, a majority of patients (n = 11, 73%) reported experiencing significant fatigue since their diagnosis, and most (n = 7, 64%) thought of their fatigue as a physical manifestation as opposed to mental (n = 1, 9% mental; n = 3, 27% both). Patients' estimates of the extent to which they thought of their fatigue as physical averaged 72% (range 40–99). Two-thirds reported that fatigue was different than lack of energy, but patients were unable to offer any consistent distinction between the two concepts. When asked to volunteer symptoms that were not on the list, patients failed to generate any new candidate disease-related symptoms.

Validation of FKSI-DRS

The mean of the FKSI-DRS scores was similar at all three time points: 29.1 (SD = 5.4) at time 1, 29.5 (SD = 4.7) at time 2, and 29.2 (SD = 5.3) at time 3.

Reliability

The FKSI-DRS showed high internal consistency at the baseline assessment (Cronbach's alpha [α] = 0.78), time 2 assessment (0.75), and time 3 assessment (0.78). Cronbach's alpha at all time points exceeded 0.70, which is a common minimum standard for internal consistency reliability, and suggestive that the FKSI-DRS can be used as an independent measure of disease-related symptoms and functioning. The stability of the FKSI-DRS over time was high, with an ICC of 0.85 between time 1 and time 2 (range of possible values = 0.0–1.0). Thus, the symptom index shows high test–retest reliability between baseline and 3–7 days post baseline.

Convergent validity.  The associations between FKSI-DRS, FACT-G and subscale scores were evaluated using Spearman correlations. Because it captures physical symptoms of disease, the FKSI-DRS was expected to be most highly correlated with the PWB subscale of the FACT-G, and correlated to a slightly lesser extent with the FWB domain compared with psychosocial (EWB and SWB) scores. Indeed, this was the case at both time 1 and time 3, with very high correlations between FKSI-DRS and PWB scores (r range = 0.84–0.85) and FWB scores (r range = 0.69–0.71). As would be expected because of its content of disease-related physical symptoms, correlations between FKSI-DRS and EWB and SWB were low to moderate (r range = 0.30–0.52). The FKSI-DRS contains two PWB items. Therefore, these correlations were inflated by redundancy. Nevertheless, even after redundancy was removed and the FKSI-DRS was correlated with an abbreviated PWB score, removing all overlap, correlations remained comparable. The FKSI-DRS correlation with the five-item PWB at both time 1 and time 3 was 0.78. In all cases, including those corrected for overlap, correlations between FKSI-DRS and FACT-G scales were significant at P < 0.0001 with the exception of SWB at time 3, which was significant at P < 0.001.

Discriminant (known-groups) validity.  The ECOG PSR was trichotomized into PSR = 0, PSR = 1, and PSR > 1. For the FKSI-DRS, all scores across PSR groups were in the appropriate direction, that is, patients with the lowest PSR (i.e., best performance status) had the highest FKSI-DRS scores (i.e., greater well-being and symptom status), and those with higher PSR had FKSI-DRS scores reflecting poorer well-being and symptom status (Table 3). Based on cross-sectional analyses, the FKSI-DRS differentiated patients grouped by PSR (P < 0.0001). Effect sizes were calculated for group comparisons to provide an indication of the clinical significance of group differences. Following Cohen's guidelines for effect sizes [12], effect sizes for adjacent PSR groups were moderate to large for the FKSI-DRS (e.g., 0.69–1.01).

Table 3.  Effect sizes of FKSI-DRS: cross-sectional (baseline) scores by ECOG performance status and longitudinal scores by GRCS
ScaleECOG PSRnMean (SD)Common SDGroup comparisons
GroupMean differenceEffect size*P-value
  • *

    Calculated for adjacent categories.

  • Difference is between GRCS Worse versus Same and Better; no difference between Same and Better. Worse: GRCS < −1; Same: GRCS −1 to +1; Better: GRCS > 1.

  • FKSI-DRS score change: score at time 3 minus score at time 1 (baseline).

  • ECOG PSR, Eastern Cooperative Oncology Group Performance Status Rating; FKSI-DRS, Functional Assessment of Cancer Therapy—Kidney Symptom Index: Disease-Related Symptoms; GRCS, Global Rating of Change Scale.

FKSI-DRS06532.70 (2.91)5.400–15.481.01<0.0001
15027.22 (4.16) 0–29.221.71 
22523.48 (6.02) 1–23.740.69 
FKSI-DRS changeWorse13−3.15 (3.18)3.9Worse vs. same−3.11−0.800.0024
Same108−0.04 (3.72) Same vs. better−2.34−0.60 
Better102.30 (4.74) Worse vs. better−5.45−1.40 

Responsiveness to clinical change.  Changes in FKSI-DRS scores were calculated by subtracting patients' time 1 scores from the time 3 scores. Patients' GRCS scores were categorized as “worse,”“same,” or “better” by collapsing GRCS domain scores that were rated on a 15-point scale (−7 through 0 to +7). As a result of sample size restrictions at the extremes of change, all gradations of change were collapsed into one “changed” category for worse and one category for better. GRCS scores were categorized as “worse” if they were rated <−1, “same” if rated −1 to +1, and “better” if rated >+1. ANOVA techniques were used to compare mean change scores on the FKSI-DRS between categories of change (better, same, worse) in each anchor variable (GRCS domain). It is important to note that the practice of pooling all globally changed patients into one group will extend the magnitude of change beyond “minimal,” because itincludes categories of change that exceed minimal by the patient's own judgment.

Changes in FKSI-DRS scores were in the anticipated direction, such that patients who rated themselves as worse on the GRCS had worsening scores on the FKSI-DRS (Mean [SD] = −3.15 [3.18]), patients who rated themselves as improved on the GRCS tended to have improvements in the FKSI-DRS (2.30 [4.74]), and patients who reported remaining the same on the GRCS tended to have change scores for most subscales scores that were in between the two other groups (= −0.04 [3.72]) (see Table 3). In addition, changes in FKSI-DRS scores were significantly different between the “worse” versus “same” and “better” groups (F2,128 = 6.34, P = 0.0024).

Estimating important differences.  Distribution- and anchor-based methods were used to estimate FKSI score changes that represent “clearly” important differences (CIDs) and that might approximate MIDs. Distribution-based estimates included 1/2 SD, 1/3 SD, and 1 standard error of measurement (SEM). Anchors used were the PSR and the GRCS. Because of the course nature of the clinical anchors and the collapsing of changes of any magnitude into one group, we considered them to provide conservative estimates of CIDs rather than being MIDs. Table 4 displays the distribution-based estimates of these differences at baseline, time 3 and change from baseline to time 3. The full range of distribution-based MIDs for the FKSI-DRS was 1–3 points, with most estimates in the 2–3 point range.

Table 4.  Distribution-based estimates of minimally important differences (MIDs) for FKSI-DRS
 n1/3 SD1/2 SDCriterion SEMLikely range of MID
  1. SEM = σx (1 − rxx)1/2.

  2. σx = the standard deviation of the scale/aggregate score.

  3. rxx = the reliability (internal consistency) of the scale/aggregate score.

  4. FKSI-DRS, Functional Assessment of Cancer Therapy—Kidney Symptom Index: Disease-Related Symptoms.

FKSI-DRS
 Baseline1411.802.702.112–3
 Time 31311.762.652.07 
 Baseline to time 3 change1311.301.95  

Cross-sectional (PSR) anchor-based criteria yielded larger estimates, again not necessarily reflecting MIDs. As displayed in Table 3, effect sizes for baseline scores of adjacent PSR groups ranged from 0.69 to 1.01 (approximately 4–5 points) for FKSI-DRS. The GRCS was analyzed as a longitudinal clinical anchor to determine MIDs. The longitudinal anchor-based criteria yielded estimates closer to the distribution-based estimates, with effect sizes for adjacent GRCS groups ranging from 0.60 to 0.80 for FKSI-DRS (approximately 2–3 points).

The effect sizes for the cross-sectional and longitudinal anchor-based CID estimates using PSR for FKSI-DRS are in the moderate to large range [12]. Change scores associated with effect sizes >0.50 (moderate) exceed what would be considered minimal. Reconciling the rather large effect sizes of the anchor-based comparisons with the smaller distribution-based estimates, it is reasonable to suggest 2–3 points as the MID range for the FKSI-DRS.

Discussion

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

The objective of this study was to develop and validate the FKSI-DRS, a brief scale to assess kidney cancer-related symptoms. The FKSI-DRS was derived from the FKSI-15, which is comprised of symptoms and concerns rated by patients and clinicians to be the most important to monitor when treating advanced kidney cancer.

Fourteen of the 15 FKSI items rated by expert providers as primarily disease-related were accepted by patients as such, and patients added fatigue to the eight-item list they were shown based on the interim (n = 18) results of the expert survey. Interestingly, results from the completed (n = 31) expert survey also included fatigue and, marginally, lack of energy. Because this is an important area to kidney cancer patients, and people differ on how they might distinguish fatigue from “lack of energy,” we have retained both fatigue-related items in the FKSI-DRS. The other symptom area that allocates two items in the FKSI-DRS is pain, which also seems fitting based on a survey of National Comprehensive Cancer Network providers indicating these are the two most important symptoms in advanced solid tumors [13]. Appetite loss might arguably have a place on the list; however, experts failed to rate appetite as any more disease-related than treatment-related in this disease. In contrast, weight loss was seen as more clearly disease-related. One of the surveyed patients also indicated that having weight loss on the list covers appetite to a significant degree. Finally, we decided to remove the “worry” item even though experts stated almost unanimously that it is related to disease and not treatment. Worry is clearly a very important concern to people with cancer. Nevertheless, unlike all of the other symptoms selected, it is unlikely that worry is caused by tumor invasion or metastasis in a direct biological way. Rather it is an emotional reaction to symptoms or concern over one's condition or outlook. New therapeutics are unlikely to be approved because they make people worry less, and indeed it is usually the case that people feel some relief from worry when they embark on any new and hopeful treatment course. We wish to minimize in this index the recording of the emotional boost one gets from starting and proceeding through a course of chemotherapy for advanced disease. As we are unable to locate in the literature a direct link between worry (a psychological concept) and tumor invasion or metastases, we felt it most appropriate to exclude the question.

The FKSI-DRS performed well psychometrically. The internal consistency reliability coefficients at all time points exceeded acceptable standards. There was evidence of convergent, divergent and known-groups validity. The FKSI-DRS demonstrated responsiveness to change in clinical status over time, and it successfully differentiated patients who reported improvement, no change or worsening in their status across multiple FACT-G domains. Cross-sectional and longitudinal distribution-based criteria suggested estimates of MIDs for the FKSI-DRS of 2–3 points. Cross-sectional and longitudinal anchor-based criteria were suggestive of larger clinically important differences, reflecting large effects in excess of the likely MID. We suggest 2–3 as the MID range for the FKSI-DRS. This study was limited in the sense that the FKSI-DRS scale analyzed was administered as a full FKSI-15 scale rather than as a simplified FKSI-DRS. We therefore assume that extraction of FKSI-DRS item responses from the FKSI-15 administration accurately reflects what people would answer had they only reported the FKSI-DRS. Interested investigators can either administer the full FKSI-15 or extract FKSI-DRS scores as we did, or re-evaluate the FKSI-DRS in a second validation effort with only these nine questions.

In conclusion, the nine-item FKSI-DRS appears to be a reasonably concise list of symptoms caused by kidney cancer. The FKSI-DRS is an index to gauge treatment impact on the most important symptoms, from the perspective of both patients and clinical experts.

Source of financial support: Supported in part by unrestricted grants from Pfizer and Bayer Pharmaceuticals.

References

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  8. Appendix
  • 1
    Coons S, Kaplan R. Assessing health-related quality of life: application to drug therapy. Clin Ther 1992;14:8508.
  • 2
    Fish L, Lewis B. Quality of life issues in the management of ovarian cancer. Semin Oncol 1999;26(Suppl. 1):S329.
  • 3
    Sutherland H, Lockwood G, Boyd N. Ratings of the importance of quality of life variables: therapeutic implications for patients with metastatic breast cancer. J Clin Epidemiol 1990;43:6616.
  • 4
    Chang V, Hwang S, Feuerman M, Kasimis BS. Symptom and quality of life surveys of medical oncology patients at a Veterans Affairs Medical Center: a role for symptom assessment. Cancer 2000;88:117583.
  • 5
    Cella D, Yount S, Du H, et al. Development and Validation of the Functional Assessment of Cancer Therapy—Kidney Symptom Index (FKSI)©. J Supp Oncol 2006;4:1919.
  • 6
    Cella D, Tulsky D, Gray G, et al. The Functional Assessment of Cancer Therapy (FACT) Scale: development and validation of the general measure. J Clin Oncol 1993;11:5709.
  • 7
    Zubrod C, Schneiderman M, Frei E, et al. Appraisal of methods for the study of chemotherapy of cancer in man: comparative therapeutic trial of nitrogen mustard and triethylene thiophosphoramide. J Chronic Dis 1960;11:733.
  • 8
    Jaeschke R, Singer J, Guyatt G. Measurement of health status: ascertaining the minimal clinically important difference. Controll Clin Trials 1989;10:40715.
  • 9
    McHorney C, Kosinski M, Ware J Jr. Comparisons of the costs and quality of norms for the SF-36 health survey collected by mail versus telephone interview: results from a national survey. Med Care 1994;32:55167.
  • 10
    Lydick E, Epstein R. Interpretation of quality of life changes. Qual Life Res 1993;2:2216.
  • 11
    Guyatt G, Osoba D, Wu A, et al. Methods to explain the clinical significance of health status measures. Mayo Clin Proc 2002;77:37183.
  • 12
    Cohen J. Statistical Power Analysis for the Behavioral Sciences (2nd ed.). Hillsdale, NJ: Lawrence Erlbaum Associates, 1988.
  • 13
    Cella D, Paul D, Yount S, et al. What are the most important symptom targets when treating advanced cancer? A survey of providers in the National Comprehensive Cancer Network (NCCN). Cancer Invest 2003;21:52635.

Appendix

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

Appendix I

FKSI—Disease-Related Symptoms (FKSI-DRS)

Below is a list of statements that other people with your illness have said are important. By circling one (1) number per line, please indicate how true each statement has been for you during the past 7 days.

 Not at allA little bitSomewhatQuite a bitVery much
I have a lack of energy01234
I have pain01234
I am losing weight01234
I have bone pain01234
I feel fatigued01234
I have been short of breath01234
I have been coughing01234
I am bothered by fevers01234
I have had blood in my urine01234