| Parkinson's Disease |
Introduction Parkinson's disease is a disorder that affects nerve cells, or neurons, in a part of the brain that controls muscle movement. In Parkinson's, neurons that make a chemical called dopamine die or do not work properly. Dopamine normally sends signals that help coordinate your movements. No one knows what damages these cells. Symptoms of Parkinson's disease may include:
As symptoms get worse, people with the disease may have trouble walking, talking or doing simple tasks. They may also have problems such as depression, sleep problems or trouble chewing, swallowing or speaking. Disease Description Parkinson's disease (PD) belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The four primary symptoms of PD are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. PD usually affects people over the age of 50. Early symptoms of PD are subtle and occur gradually. In some people the disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of PD patients may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions. There are currently no blood or laboratory tests that have been proven to help in diagnosing sporadic PD. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases. Agency Guidelines There is no special FDA guideline for drug approvals for Parkinson's Disease. In September 2008 the EMA published a guideline Guideline on Clinical Investigations of Medicinal Products in the Treatment of Parkinson's Disease which became into effect in February 2009. Clinical Trial Endpoints from National Parkinson Foundation Parkinson’s Disease Rating Scales. Several rating scales have been developed to measure the impact of PD on a patient and family. These scales are used in research to determine eligibility to participate in a research trial or to assess severity and disease progression. Scales may also be used in clinical practice to identify and monitor problems or gauge clinical function and degree of progression. PD Evaluation Scales
Quality of Life Assessment in PD
Cognitive Assessment in PD
Sleep Assessment in PD
Mood and Behaviour
Other
Clinical Trial Design
Data Challenges Prior and Concomitant Medication One of the data challenges in the PD indication are prior- and concomitant medication. Since patients who suffer from PD are mostly elderly patients who either suffer from other diseases or have to take combinations of several other treatments for PD (e.g. Levodopa) some data challenges occur with Prior- and Concomitant medication. Especially the use of Levodopa is part of the protocol criteria in patients with advanced PD. In clinical trials patients need to be on a stable dose within a defined time interval prior to the first study treatment. One of the challenges is to well define this stability criteria. The following issues can occur and it has to be defined what stability means:
Exposure Based on the disease severeness patients who suffer from PD need to follow a dosing schedule which requires multiple tablet intakes. Often patients also have to take dosages during the night. Due to these facts the collection, cleaning and analysis of exposure data is more challenging than in indications which require once or twice daily doses. There are also treatments like once daily patches which require special attention. Since patches can detach the collection of the actual adhesiveness can be challenging as well. Patient Reported Outcomes Data Collection Recently the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institutes of Health (NIH) founded an external working group of about 70 experts to develop Common Data Elements (PD CDEs). These are now ready for feedback from the lager PD clinical research community, see Common data Elements Parkinson's Disease for more details. Like projects for other diseases like Epilepsy the CDE project strives to create content related standards for the data collection. The PD CDE is focussed on the most important elements to collect data, share it and analyze it through collaboration of the PD research community. SDTM Data Right now there is no special SDTM Domain for the indication PD. Since most of the measured efficacy data is based on findings the data should be stored in the Findings About (FA) SDTM domain. ADaM Data Most of the measured efficacy data for PD is collected in questionnaires which are stored in SDTM.QS. The combination of all CRF data from SDTM.QS with derivations for analysis in the corresponding ADaM datasets can easily lead to extremely huge datasets. It is reasonable to split the single efficacy measurements in single ADaM datasets. References
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