Clinical research is an organized method of acquiring knowledge about the cause and course of a disease and the outcome of treatment. The types of clinical research for Chiari I malformation and/or syringomyelia can be divided into 1) natural history (observational), and 2) treatment (interventional) studies.
Natural history studies. This type of study acquires general information about a disease. This research includes epidemiologic studies that provide a summary of information about a large number of patients with the disease. Such studies in the field of Chiari I malformation and syringomyelia can identify the proportion of the general population (prevalence) that have Chiari I malformation and syringomyelia, and the proportion of these that have serious manifestations including pain, paralysis, loss of sensation, sleep apnea, and cloudy thinking that impair quality of life. They can also identify other health factors that might influence the development and severity of manifestations of Chiari I malformation and syringomyelia.
Genetic studies. These are natural history studies that explore the influence of genetic factors on the development of Chiari I malformation. Clinical genetics research may provide insight into how small variations in genes (mutations) may favor development of Chiari I malformation and the risk of other family members having the malformation (https://clinicaltrials.gov).
Diagnostic studies. Clinical research based on MRI and diagnostic studies are also common. Research based on MRI CSF flow studies is another type of natural history study that explores factors that may foster the development or severity of syringomyelia. Non-invasive CSF flow studies may increase understanding of the pattern and effects of CSF flow disruption in patients with Chiari I malformation and syringomyelia. Taking knowledge gained from these studies, strategies can be designed that target key abnormalities that influence the development or severity of Chiari I malformation and syringomyelia. Treatment can potentially be instituted that reduces the risk of developing the disease, reduces its severity, and/or improves its treatment.
The quality and amount of knowledge gained about a condition such as Chiari I malformation and syringomyelia is largely dependent on the amount of forethought and organization devoted to a research project. Prospective research describes, before the study begins, what type of patient will be included, what research questions will be asked, and what research tests will be performed. This type of study provides more reliable information than retrospective studies, which decide after the fact, what type of patient will be included, and which acquire medical information from review of medical records of patients that have already received standard medical care. Retrospective natural history studies of syringomyelia patients have documented that without treatment, most patients will experience gradual, stepwise neurological deterioration (increasing weakness, sensory loss, chronic pain, or other symptoms) over many years.1,2
A prospective treatment study in children with Chiari I malformation and syringomyelia is currently underway. This prospective study will be able to provide more accurate information than past retrospective studies. The researchers will compare surgical outcomes from posterior fossa decompression (PFD) and posterior fossa decompression with duraplasty (PFDD). These are the two most common surgical interventions for Chiari I with or without syringomyelia. Currently, this surgery is performed in equipoise, which means doctors do not know which treatment method is better. The research is fair because based on current knowledge, patients in the study have an equal chance of having a favorable outcome regardless of which type of decompression they receive. This study will help determine, once and for all, which surgery is better—or if there really is no difference.
All prospective (and some retrospective) clinical research studies require approval by an Institutional Review Board (IRB) before they start enrolling patients. The purpose of the IRB is to protect subjects of clinical research by assuring that risks are minimized, that benefits are maximized, and that risks are reasonable in terms of the anticipated benefits of the study. Institutional Review Board (IRB) oversight of the research protocol (document describing the research) continues throughout the life of the protocol. The IRB assures that participation in clinical research is voluntary and not a condition of receiving standard healthcare. Patients must give their informed consent before they participate in IRB-regulated research, which means that they 1) are informed in writing of the risks and possible benefits of the protocol, 2) are given time to ask questions, 3) sign the Consent document, and 4) receive a copy of their signed Consent document. The Consent document should describe if the benefit of research is limited to acquisition of knowledge about the patient’s condition or if there is the prospect of direct benefit (improved health) to the patient. Only patients that meet specific scientific requirements known as Inclusion and Exclusion Criteria may enroll in the research study. Continued participation in the study remains voluntary, with the subject being free to withdraw from the study at any time. Clinical research studies are reviewed at least annually by the IRB. Although oversight of clinical research may sometimes appear to be unnecessarily cumbersome and burdensome, clinical researchers realize that the system ensures that subjects of research are protected and that research can provide scientifically valid results (https://jama.ama-assn.org/cgi/content/abstract/283/20/2701).
Many (but not all) federally and privately supported clinical trials are registered with ClinicalTrials.gov https://clinicaltrials.gov and trials of interest can be found using appropriate search terms such as “Chiari” or “syringomyelia.” https://circ.ahajournals.org/cgi/content/full/circulationaha;111/10/1337.
Patients are encouraged to speak with their healthcare providers before enrolling in clinical research protocols.