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Parkinson's Disease Questionnaire - 39 (PDQ-39) as the Primary Outcome Measure Quality of life (QoL) has become an important construct in the assessment and treatment of Parkinson’s disease (PD). QoL has been recognized as an important aspect of determining the effectiveness of interventions and treatment. In other words, the medical and scientific community has validated the importance of assessing not only the physical and neurological aspects of change and improvement affected by a treatment, but are interested in knowing how the intervention impacts patients’ and caregivers’ lives as well. The importance of the patient’s perspective has been recognized, and increasingly, the spouse or caregiver’s perspectives as well. Quality of life can incorporate a number of specific variables which can be subsumed under several domains such as physical functioning, emotional well-being, and social support. Health-related quality of life is more specific as it refers to the impact of health conditions on overall functioning (Kaplan, Anderson, Wu, Mathews, Kozin, & Orenstein, 1989). In clinical medicine, QoL refers to the patient's own perception and self-evaluation regarding the effects of an illness and its consequences on his or her life (Martinez-Martin, 1998). The assessment of QoL can be done using general or disease-specific measures. Considering QoL is also important in determining whether adjunctive treatments may be helpful for patients and families coping with PD. If quality of life is “poor” in spite of the best neurological care and adjustment of medications, medical personnel may want to consider what can be done to improve the patient’s situation. The assessment of QoL can be done using general or disease-specific measures. Several criteria for good measurement of quality of life in patients with PD have been suggested. These include reliable, valid, and simple instruments that are easily administered and interpreted. Measures should reflect areas that are important to the patient, include measurement of physical and psychological health, and the presence of summary scores which are appropriate for statistical analyses (de Boer, Wijker, Speelman, & de Haes, 1998). A growing number of measures have been created and utilized to assess medical patients’ perspective of the impact of medical diseases, including Parkinson’s disease, on quality of life. These particular types of measures are critical to the medical treatment and outcome of patients as they incorporate the individuals’ own perceptions of their health (Schrag, Jahanshahi, & Quinn, 2000). There are primarily two types of quality of life measures, generic and disease-specific, which may be used depending on the population and investigation purposes. Generic measures are intended to be applicable for a wide range of health problems and diseases, while disease-specific measures assess quality of life aspects for a given disease, population, or condition of interest (Martinez-Martin, 1998). Instruments which contain items specific to a particular disease are more likely to be relevant to areas that clinicians may wish to monitor and obtain higher levels of responsiveness from patients because their content is particularly important to patients (Guyatt, Feeny, & Patrick, 1993). Several criteria for acceptable measurement of quality of life in patients with PD have been suggested. These include reliable, valid, and simple instruments that are easily interpretable, with questions or content that reflects important areas to the patient, measurement of physical and psychological health, and the presence of summary scores which are feasible for statistical analyses (de Boer, Wijker, Speelman, & de Haes, 1998). In addition to reliability and validity, responsiveness and reproducibility should also be evaluated. Responsiveness refers to how sensitive the measure is to changes in health status. Statistical procedures can be used to determine if a particular measure is capable of detecting such changes (Jenkinson, Fitzpatrick, & Peto, 1999). As opposed to the focus on “motor” related outcome measures as contained in the gold standard of PD scales, the Unified Parkinson’s Disease Rating Scale (UPDRS). There is a growing consensus that the “non motor” manifestations of the disease play a bigger role in detrimentally impacting a patient’s QoL. Non-motor symptoms vary from person to person, but can include sleep abnormalities, fatigue, behavioral and cognitive impairments, anxiety, depression, autonomic dysfunction, gastrointestinal problems, and pain. Speech, which is a motor function, is often included in the context of non-motor manifestations, since it responds differently than limb movement to pharmacologic and/or neurosurgical intervention. The clinical community also recognizes psychosis as a non-motor complication of PD, although it is believed to be a complication of PD medications, rather than of the disease itself. (NINDS: 2006 Parkinson’s Disease Research Plan: 12-13). Accordingly, an instrument that purports to contain a comprehensive measure of a PD patient’s QoL must employ domains across many more areas than the standard “motor symptoms” of the UPDRS. In response to the rising evidence for the importance and significance of evaluating HRQoL and considering patient reported outcomes (ie PRO’s) in clinical observations, the FDA issued a Guidance for Industry document titled: FDA: Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. 2/06. (www.fda.gov/cder/guidance/5460dft.pdf). The information set forth in this guidance document has been applied in the development of this clinical study protocol. Specifically, one factor in the decision to utilize the PDQ-39 as the primary outcome measure for this clinical study is its ability to satisfy the HRQoL assessment criteria specified in the FDA reference document including reliability, validity, ability to detect minimally meaningful change and interpretability.” This FDA reference document is contained in full in Appendix D of this document. A disease specific, 39-item QoL instrument for use with patients with PD, the Parkinson’s Disease Questionnaire (PDQ-39), has been shown to not only have good reliability and validity, but to also demonstrate consistent responsiveness and reproducibility (Fitzpatrick, Jenkinson, Peto, 1997; Fitzpatrick, Peto, Jenkinson, 1997). In addition to its impressive psychometrics, the PDQ-39 is uncomplicated to interpret and provides the ability to assess the overall impact of the illness. Consequently, the PDQ-39 is the most widely used disease-specific patient completed rating scale in PD and has been widely used in many trials to assess the effectiveness of treatment (Fitzpatrick, Jenkinson, Peto, 1997; Hagell & Nygren, 2007; Schrag, Jahanshahi, & Quinn, 2000). Additionally, the NINDS in its NET-PD project is utilizing the PDQ-39 to standardize outcome measures that it hopes will prove more inclusive in terms of QoL and non motor aspects of PD, than the UPDRS scale. (NINDS: 2006 Parkinson’s Disease Research Plan: 12-13) The PDQ-39 was developed following exploratory, in-depth interviews with patients attending PD neurology outpatient clinics in the UK, where patients were asked to describe areas of their lives that have been adversely affected by their PD (Peto, Jenkinson, & Fitzpatrick, 1998). Based on these interviews and discussions with patients, items were created and a questionnaire was developed. Factor analyses revealed the presence of eight discrete factors, or dimensions: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, and communication (Peto, Jenkinson, & Fitzpatrick, 1998). The PDQ-39 has been used as an outcome measure in numerous clinical trials to test effectiveness and clinical significance of many surgical, pharmacological and psychological treatments (Deuschl, et al., 2006; Martinez-Martin, et al., 2002). And is currently the primary outcome measure for a phase III conversion study involving Pramipexol to Ropinirole Controlled Release (CR) sponsored by the University of Kansas (clinicaltrials.gov identifier NCT00275275). PDQ-39 Item Domains and Questions:
Mobility
Activities of daily living
Emotional well-being
Stigma
Social support
Cognition
Communication
Bodily discomfort Although statistical significance of changes in quality of life is important in clinical trials, determining the clinical significance or meaning of these changes is somewhat more challenging. Such a problem can be overcome if the minimal important differences between times points are known. Minimally important differences are the smallest change of scores that are subjectively meaningful to the patient. For example, Peto, Jenkinson & Fitzpatrick (2001) suggested the importance of assessing the minimum magnitude of change across time points in the PDQ-39 that should be sought when studies and clinical trials seek to evaluate change in QoL over time in Parkinson’s disease. In their anchor based study, significant mean change scores on the PDQ-39 subscales ranged from 11.4-1.6 at follow-up and included six of the subscales (i.e., Mobility, ADL’s, Emotional well-being, Stigma, Social Support, and Communication) and the Overall score (Peto, Jenkinson, & Fitzpatrick, 2001). In sum, the level of change required differs greatly across the dimensions and the primary QoL variable of interest should be determined when designing trials and determining appropriate sample size calculations (Peto, Jenkinson, & Fitzpatrick, 2001). As opposed to the above described “anchor based” approach to determining minimal clinically significant changes, we may look to a couple of distributional approach methods. The first is the level of effect size that reflects such meaningful change on the PDQ-39. Traditionally, effect sizes of 0.2 are often regarded as small, but research suggests that such changes appear to be subjectively meaningful to patients (Peto, Jenkinson, & Fitzpatrick, 2001). A more conservative approach is that of “Standard Error of Measurement” or (SEM). In a recent PD review authors utilized a convergence across both samples and methods (anchor based and distributional) in identifying minimal meaningful changes for the PDQ-39, and its subscales. Accordingly, for the Summary Index Score and subscales particularly appropriate for this trial, a one SEM value would reflect
a. Summary Index: 3.98 Based on its rigorous development, outstanding psychometric qualities, and its ability to accurately assess the impact of PD from the point of view of the patient, the PDQ-39 is one of the most widely used and validated QoL outcome measures available and rapidly becoming the QoL questionnaire of choice for PD research (Hagell & Nygren, 2007; Peto, Jenkinson, & Fitzpatrick, 1998). Not only has the PDQ-39 been shown to be more sensitive to the specific concerns of individuals with PD, it has also been found to correspond to clinicians’ judgments of change over time (Fitzpatrick, Peto, & Jenkinson, 1997). And has been found to be significantly correlated with the UPDRS score, Hoehn & Yahr index, and Columbia Rating scale (Martinez-Martin, Frades Payo, 1998). The PDQ-39 has consistently demonstrated its utility and appropriateness for the use in clinical trials (Jenkinson, Fitzpatrick, & Peto, 1999).
The authors conclude and suggest that another assessment category should be added to all future trials in PD, the effect of an intervention on the Health Related Quality of Life emphasis added ( Martinez-Martin, Deuschl, 2007). We agree with the above, and propose that the Summary Index score of the PDQ-39 is an appropriate primary outcome measure for this clinical trial. References de Boer, A.G., Wijker, W., Speelman, J.D., de Haes, J.C. (1998). Quality of life in patients with Parkinson’s disease: Development of a questionnaire. Journal of Neurology, Neurosurgery & Psychiatry, 61, 70-4. |
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Patients who have been diagnosed with Parkinson’s disease, and are able to travel to Novi, Michigan, northwest of Detroit, should be aware of the clinical trials that are currently being conducted there. As part of these clinical trials, Parkinson’s patients will undergo a form of magnetic pain therapy, which requires the body to be surrounded by a low strength magnetic field. These trials will be used to test the ability of a new Resonator® device in diminishing the effects of Parkinson’s disease. Once the patient qualifies for and completes the clinical trial, they will be compensated. Novi, Michigan is located in Oakland County and just 30 minutes northwest of Detroit. This office also serves the counties of Wayne and Macomb. Interested parties can contact Pico-Tesla for more information. |
