The European Medicines Agency (EMA) has released a draft guideline for the clinical investigation of products intended to treat multiple sclerosis (MS), a neurological disease characterized by the body attacking its own fatty myelin sheaths, disrupting and damaging the body's ability to communicate with itself.
The guideline-similar in principle to most released by EMA-establishes a set of recommended approaches to clinical development, with a particular focus on study designs, populations, primary endpoints and the duration of the trial.
Current treatment models for MS focus on alleviating its symptoms, treating acute relapses of the disease and preventing future relapses. At present, no cures have been developed and relatively little is known about the disease's underlying causes.
Because the underlying goal of treatments may be different, EMA concedes that products with different goals may well have different clinical development plans and trial designs. Studies which aim to prevent relapses, for instance, may need to last three years, while one that treats acute symptoms would only require a fraction of that amount of time to complete.
Trials Depend on the Patient
The risk-benefit balance of any product must also be taken into consideration, particularly if it is intended to be used over the long term. Explains EMA: "The reason is that so far the more effective agents also have an increased risk of opportunistic infections and malignancies, among other safety issues."
Accordingly, patients should be enrolled in studies based on the risk of the drug and their need for a particular treatment.
For example, drugs with mild safety profiles should be used in patients with a benign course of MS or early-stage MS, while treatments with the potential to disrupt the immune system should be reserved for patients in advanced stages of the disease or with severe symptoms.
Efficacy, at least, is slightly more straightforward. New compounds should be tested in a randomized, double blind-controlled superiority study using either a placebo or first-line treatment control group in parallel.
Drugs will be assessed in relation to their intended effect against MS. For instance, treatments that are intended to prevent acute relapses or reduce their severity will be assessed on their ability to do both relative to a first-line treatment or placebo. Secondary endpoints may also be considered, including general disability, cognitive impairment and fatigue.
Patient's progress will be assessed using the Kurtz's Expanded Disability Status Scale (EDSS), a scaled assessment of disabilities related to MS. Though the scale has its disadvantages, EMA said it is useful as a source of comparison to other established studies. Other scales may be used concurrently, it added. Other assessments may require more advanced tools, such as magnetic resonance imaging (MRI) to detect the presence of cognitive impairments.
Consultation on the document, entitled Guideline on clinical investigation of medicinal products for the treatment of Multiple Sclerosis, ends 9 April 2013.