The aim of this pilot study was to design a multidimensional PRO assessment tool for PD patients scheduled for an invasive therapy, and then to assess its practicality in application and potential clinical utility at both group and individual level. The measure is novel in combining subjective perceptions of symptom difficulty with expectations of treatment outcome. Despite the small numbers of patients assessed, we have shown that such a scale can be pragmatic to use, even in a complex multimodal disease, such as PD, and that it is able to provide clinically meaningful information to supplement routine clinical assessment. This approach allowed us to determine for each individual a map of the patient’s perceptions of their disease and their expectation from treatment, and offer the potential to help manage patients in preparing them for therapy.
Traditionally, the measurement of improvement of parkinsonism by therapy has been by measuring motor signs and broad measures of outcome, such as health-related quality of life [13, 14], The multiplicity of symptoms in PD means that motor scores are not sufficient to describe overall quality of life [3, 9, 15]. The impact of therapies on the other aspects of PD is generally less well understood and has been explored less than motor state [15–17]. This is in line with data from others and our group that suggests that standard PD severity scales are an insufficient measure of disease burden. Indeed, the “gold standard” Unified Parkinson’s Disease Rating Scale (UPDRS) has been modified to the “new UPDRS” (MDS-UPDRS) for this reason [8]. Despite an improvement as measured by standard scales, patients may describe being unhappy after DBS [16, 18]. Conversely, patients may be very satisfied despite modest clinical gain. From our department, we have noted a patient whose main desire for treatment of her PD was the ability to “sit still and sew” [19]. Her degree of satisfaction following DBS (“very pleased”) was not matched by the minor improvement (< 10%) in the UPDRS score. It is debatable which outcome measure was the more clinically relevant. Further, the assessment of “success” from a therapy can become more complex if one were to extend analyses to include a more “complete” assessment of stage of life, which would include social dynamics including relationships/marriage [20]. Measuring treatment effects on one symptom (e.g. tremor), or set of symptoms (e.g. the ability to move), is insufficient to determine if a therapy is multi-dimensionally beneficial for a patient, cohort or population, unless it is known that it is that symptom (or set of symptoms) which is personally significant to the patient. For example, we have observed that despite “successful” DBS as determined by the patient, neurologist, neuropsychologist, neuropsychiatrist and family practitioner, a carer remained unhappy because the partner had “changed”, no longer needing such intensive support from the carer, leading to a mutually acceptable marriage breakdown. In this complex circumstance, should the treatment be considered “successful”? Should it be offered to similar patients?
The PRO concept informing the present study is a move away from assessments based on the clinical aim of “fixing” the symptom/sign, and towards selecting treatments that are best able to address a patient’s priorities across the range of PD-related problems and their impact. The concept is powerful and yet pragmatic, and is in line with trends that encourage patient inclusion in treatment decisions. This is a simple means of assessing the results of severity and expectation for individuals and its meaning to the patient [6]. Utilization of any PRO does not move away from the need to use standard severity scales, nor generic or specific quality of life scales. However, they can help clinicians and researchers, jointly with the patient, to understand better the impact of symptoms and proposed treatments (rather than the physiological effect of treatment on the sign). PRO-APD draws on three decades of experience in the assessment of other chronic multifactorial disorders (e.g. dementia [21], schizophrenia [22] and neurorehabilitation [23]). Most importantly, there is now guidance from both the FDA and European Medicines Agency for the use of PRO measures in drug development [24] and so one expects to see their increasing use over the next generation of treatments.
As a first step, we report here the preliminary use in assessing severity and expectation in a common disease, even if it is as complex as PD. A further study is required to validate this PRO-APD and demonstrate its utility, and for assessment of objective and subjective outcomes after therapy to determine whether “expected outcome” is matched to “measured outcome”, and if not what the impact of the discrepancy might be. With further extrapolation, the measure should be equally applicable to other adult or paediatric chronic movement disorders, like essential tremor and dystonia with adjustment where necessary of the problems assessed.
Unless a PRO is intended as a surrogate for traditional conventional measures (e.g. self-report version of a clinical scale for use in surveys), strong association are not necessarily expected or even necessary. In the present case, patients were asked to assess the severity of the PD-related problems and expectations of change. Given the difference in the various scales, item content and methods of assessment, we would expect only moderate associations between self-rated problem domain severity and standard scales. This was observed for motor problems (with MDS-UPDRS part 3, shown in Table 3), NMS problems (with NMSS, shown in Table 3) and psychological and cognitive problems with (HADS but not ACE-R, shown in Table 3). This latter result suggests that the Cognitive/Psychological domain may be more sensitive to measuring mood problems in the present sample. Subjective ratings of cognition have also typically been found to be unrelated to objective measurements across the age span [25].
At a group level, there was evidence for a robust association between the perceived severity of the different problems domains and the expectations for outcome, with all patients expecting improvement or, at worse, no change. We found that the associations between severity and expectations were strongest and most reliable for the motor and non-motor symptom domains, and less robust for the cognitive and psychological problems and weakest for the social and ADL domain (See Figure 1A-D). This may reflect the patient’s model of their disease and the degree to which they linked different problems to the underlying PD, and therefore amenability to treatment. For example, one can speculate that a patient who attributes memory problems to his/her age may have different expectations from a treatment targeting PD compared with a patient who sees the memory problems as an integral feature of the disease. Helping patients to understand the nature and extent of the full range of problems associated with their PD, and the potential impact of therapy, is likely to be important in helping them make informed choices and assess the possible impact of any future treatment.
Low mood might conceivably have had an impact on expectations, with depressed and anxious patients expecting a less favorable outcome. In practice, depression and anxiety as measured by the HADS was associated positively with degree of expected change, although the effect was significant only for the cognitive and psychological problems.
Clinical outcomes from advanced treatments such as DBS, Apo and IJL can produce dramatic improvements in some patients and for some symptoms, both motor and non motor. However, not all patients show a marked improvement and not all symptoms show similar responsiveness. An assumption that the most severe (and personally significant) problems are going to improve, and by the largest extent, raises the risk that patients may be dissatisfied with the outcome [18, 26]. Identifying such misperceptions in advance offers the opportunity to provide the patient with the facts to inform and possibly adjust their expectations of treatment ahead of time. Although lack of accurate information may contribute to unrealistic expectations, individual characteristics (such as optimism) may also play an important role. Optimism is recognized as a dispositional trait that is largely independent of factors such as mood [27]. Evidence from patients with other physical conditions suggest that low levels of optimism is associated with poor outcome, perhaps because patients fail to engage with treatment or to be proactive in coping with the challenges of their condition. However, high levels of optimism may also be unhelpful if they set up expectation that cannot be met or encourage a passive ‘everything will be alright’ attitude. Practically, moderate (rather than excessively high or low) levels of optimism may be the best for outcome in chronic disease such as multiple sclerosis and Parkinson’s disease [28] and something that clinicians can encourage when discussing potential treatments.
The two cases described in this study were chosen to illustrate somewhat polarized expectations with case X having extreme levels of positive expectation for the large majority of problems experienced (which may not have been achievable), while case Y had lower expectations for some and no positive expectations for other problems. Both patients might benefit from a detailed discussion about what the planned treatment can and cannot reasonably offer. Patient Y was more depressed and had a significant degree of cognitive impairment that may have biased their judgment. However, a more pessimistic and limited set of expectations is not necessarily bad and may even be closer to the likely clinical reality. A danger of low expectation is when they cause a patient to decline available treatment options.
We note several important limitations to our study. Our study is a small pilot and further research is required to demonstrate the scale validity and utility. We appreciate the current lack of accepted consistency in meaning of the term “holistic”, and of uniform guidelines on the specific selection of one treatment modality over another, although some guidance exists, e.g. significant cognitive impairment may exclude DBS, but not always exclude IJL or Apo [4]. None-the-less, this is a pragmatic first step which exemplifies the benefits of a PRO approach, and which if developed further could help guide individual patients to be offered and accept individual therapies.
In conclusion, a PRO approach encompasses a patient-driven view of care. We present a pilot study using PRO-APD as a demonstration to provide a simple and pragmatic assessment of the severity and expectation of treatment, and which is in line with increased patient participation in their management. Patients opting for invasive therapy for PD have moderately high multi-domain symptom load, and also expect substantial improvements in multiple domains. These need to be considered when assessing patients for therapy, so that individual expectations can be realistic, since unexplored expectations are more likely to lead to overall dissatisfaction following therapy. Our findings are preliminary. Further validation could lead to the use of PRO-APD as an adjunct to existing scales in clinical management.
