Interpretation of response categories in patient-reported rating scales: a controlled study among people with Parkinson's disease.

BACKGROUND: Unambiguous interpretation of ordered rating scale response categories requires distinct meanings of category labels. Also, summation of item responses into total scores assumes equal intervals between categories. While studies have identified problems with rating scale response category functioning there is a paucity of empirical studies regarding how respondents interpret response categories. We investigated the interpretation of commonly used rating scale response categories and attempted to identify distinct and roughly equally spaced response categories for patient-reported rating scales in Parkinson's disease (PD) and age-matched control subjects. METHODS: Twenty-one rating scale response categories representing frequency, intensity and level of agreement were presented in random order to 51 people with PD (36 men; mean age, 66 years) and 36 age-matched controls (14 men; mean age, 66). Respondents indicated their interpretation of each category on 100-mm visual analog scales (VAS) anchored by Never--Always, Not at all--Extremely, and Totally disagree--Completely agree. VAS values were compared between groups, and response categories with mean values and non-overlapping 95% CIs corresponding to equally spaced locations on the VAS line were sought to identify the best options for three-, four-, five-, and six-category scales. RESULTS: VAS values did not differ between the PD and control samples (P = 0.286) or according to educational level (P = 0.220), age (P = 0.220), self-reported physical functioning (P = 0.501) and mental health (P = 0.238), or (for the PD sample) PD duration (P = 0.213) or presence of dyskinesias (P = 0.212). Attempts to identify roughly equally spaced response categories for three-, four-, five-, and six-category scales were unsuccessful, as the 95% CIs of one or several of the identified response categories failed to include the criterion values for equal distances. CONCLUSIONS: This study offers an evidence base for selecting more interpretable patient-reported rating scale response categories. However, problems associated with raw rating scale data, primarily related to their ordinal structure also became apparent. This argues for the application of methodologies such as Rasch measurement. Rating scale response categories need to be treated with rigour in the construction and analysis of rating scales.

Whose quality of life? Ethical implications in patient-reported health outcome measurement.

OBJECTIVES: Patient-reported health status questionnaires intend to assess illness and therapy from the patients' perspective. To provide fair and valid assessments, they should be equally relevant to major subsets of respondents. Furthermore, disease-specific measures are assumed to be perceived as more relevant than generic ones. This study assessed these assumptions among people with Parkinson's disease. METHODS: Cross-sectional data from 202 people with Parkinson's disease (54% men; mean age, 70) were analyzed regarding patient-rated relevance and predictors of patient-rated poor relevance of two generic [the 36-item Short Form Health Survey (SF-36) and Nottingham Health Profile (NHP)] and one disease-specific [Parkinson's Disease Questionnaire (PDQ-39)] health status questionnaire. RESULTS: There were no differences in relevance ratings across the questionnaires. Poorer overall quality of life [odds ratio (OR), 2.459] and mental health (OR, 1.023) were associated with poorer patient-rated relevance of the SF-36, and higher age was associated with poorer patient-rated relevance of the PDQ-39 (OR, 1.040). No significant predictors were found for the NHP. CONCLUSIONS: The PDQ-39 failed to meet the assumption that disease-specific scales are more relevant than generic ones. Nevertheless, the most important implication of this study is an ethical one. Because the relevance of the SF-36 and PDQ-39 is perceived as poorer by those who fare least well and by older people, these scales may not reflect the perspectives of these groups. This challenges bioethical principles and threatens scientific validity. Perceived relevance of patient-centered outcomes needs to be considered, or the voice of vulnerable groups may be silenced, fair inferences prohibited, and opportunities for improved care lost.

A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction.

A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.

Measuring fatigue in Parkinson's disease: a psychometric study of two brief generic fatigue questionnaires.

This study evaluated and compared the measurement properties of the 13-item Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and the 9-item Fatigue Severity Scale (FSS) in 118 consecutive Parkinson's disease (PD) patients, using traditional and Rasch measurement methodologies. Both questionnaires exhibited excellent data quality and reliability (coefficient alpha>or=0.9), and acceptable rating scale functionality, and both discriminated between fatigued and nonfatigued patients. Factor and Rasch analyses provided general support for unidimensionality of both FACIT-F and FSS, although they do not appear to measure identical aspects of fatigue. No signs of differential item functioning (DIF) were found for the FACIT-F, whereas potential age DIF was detected for two FSS items. These results support the measurement validity of both questionnaires in PD, although the FACIT-F displayed better measurement precision and modest psychometric advantages over the FSS. Availability of psychometrically sound fatigue measures that are applicable across disorders provides a sound basis for advancing the understanding of this common and distressing complaint.

Estimating the value of novel interventions for Parkinson's disease: an early decision-making model with application to dopamine cell replacement.

A long-term cost-effectiveness model for early decision-making and estimation of outcomes of novel therapeutic procedures for Parkinson's disease (PD) was developed based on the Hoehn and Yahr (HY) stages of PD. Results provided support for model validity. Model application to a future dopamine cell replacement therapy indicated long-term cost offsets and gains in quality-adjusted life years (QALYs) in early onset PD (HY III-IV), as compared to standard drug therapy. The maximum price premium (i.e., profit or compensation for developmental costs) for the intervention to remain cost-effective was estimated to euro12000-64000 according to cost-per-QALY thresholds of euro38000-70000 and depending on whether all or only medical direct costs are considered. The study illustrates the value of early health economic modeling and the described model shows promise as a means to estimate outcomes and aid decision-making regarding novel interventions for PD.

Factors affecting the clinical outcome after neural transplantation in Parkinson's disease.

Intrastriatal grafts of embryonic mesencephalic tissue can survive in the brains of patients with Parkinson's disease, but the degree of symptomatic relief is highly variable and some cases develop troublesome dyskinesias. Here we explored, using clinical assessment and 18F-dopa and 11C-raclopride PET, factors which may influence the functional outcome after transplantation. We observed increased 18F-dopa uptake in the grafted putamen, signifying continued survival of the transplanted dopaminergic neurons, in parallel with a progressive reduction of 18F-dopa uptake in non-grafted regions for the whole patient group. The patients with the best functional outcome after transplantation exhibited no dopaminergic denervation in areas outside the grafted areas either preoperatively or at 1 or 2 years post-operatively. In contrast, patients with no or modest clinical benefit showed reduction of 18F-dopa in ventral striatum prior to or following transplantation, which may have limited graft-induced improvement. We obtained no evidence that dyskinesias were caused by abnormal dopamine (DA) release from the grafts. As has been observed for intrinsic dopaminergic neurons, there was a significant correlation between 18F-dopa uptake and methamphetamine-induced change of 11C-raclopride binding (as a measure of DA release) in the putamen containing the graft. Furthermore, we observed no correlation between 11C-raclopride binding in anterior, posterior or entire putamen under basal conditions or after methamphetamine, and dyskinesia severity scores in the contralateral side of the body. Withdrawal of immunosuppression at 29 months after transplantation caused no reduction of 18F-dopa uptake or worsening of UPDRS motor score, indicating continued survival and function of the graft. However, patients showed increased dyskinesia scores, which might have been caused either by growth of the graft or worsening of a low-grade inflammation around the graft. These findings indicate that poor outcome after transplantation is associated with progressive dopaminergic denervation in areas outside the grafts, a process which may have started already before surgery. Also, that the development of dyskinesias after transplantation is not associated with excessive DA release from the grafts. Finally, our data provide evidence that long-term immunosuppression can be withdrawn without interfering with graft survival or the motor recovery induced by transplantation.

Resource use and costs in a Swedish cohort of patients with Parkinson's disease.

We estimated resource use and costs in patients with Parkinson's disease (PD), thereby providing baseline data for future economic evaluations of therapeutic interventions. Data were collected from medical records of a South Swedish cohort of 127 PD patients during 1 year (1996) and a mailed questionnaire inquiring about cost-related consequences and resource use in 1996 and in 2000. Annual costs were calculated based on prevalence and expressed in SEK (monetary value of the year 2000). Direct health care costs averaged approximately SEK 29,000 ( approximately USD 2,900; EUR 3,200) per patient per year, of which drugs were the most costly component. Nonmedical direct costs were higher than direct health care costs, averaging approximately SEK 43,000 ( approximately USD 4,300; EUR 4,800) per patient per year, and costs due to lost production were approximately SEK 52,000 ( approximately USD 5,200; EUR 5,800) per patient per year. The mean total annual cost for PD in our sample approximated SEK 124,000 ( approximately USD 12,400; EUR 13,800) per patient. These findings are roughly within the same range as estimates from other countries and show that PD causes a considerable societal burden. In addition to other outcomes, evaluations of the economic implications of new therapeutic interventions are highly warranted. In this perspective, the present study provides valuable baseline data.