Making Sense of MS Research

Summaries of independent,
high-quality research about multiple sclerosis treatments

Glossary

Clinically Isolated Syndrome (CIS)

Clinically isolated syndrome (CIS) is the term used to describe a single attack of MS-like symptoms that is caused by inflammation in the central nervous system. People who have experienced CIS are at risk of having a second attack and going on to develop MS.

Taken from: Understanding MS : An introduction for people living with MS, Sydney, NSW, MS Australia 2012

Confidence Interval

In studies of MS treatments, the researchers usually select only a sample of all the people with MS to take part. They use a confidence interval to help take the results in that sample of people and apply it to all people with MS.

A confidence interval presents the upper and lower boundaries of where we might expect the true effect of the MS treatment to lie. Specifically, it tells us two things:

  • If the confidence interval crosses either one or zero (depending on the statistical analysis) then the true effect of the MS treatment in the broader population could be either positive or negative. This also means that the result is not statistically significant.
  • If the confidence interval is wide, it means there is statistical uncertainty about the true size of the effect (for example it could be a large or small, or a positive or negative effect).

The confidence interval helps us to determine if the treatment is likely to be effective in the broader MS population.

Controlled Clinical Trial

A controlled clinical trial is the same as a RCT, except that the groups are not necessarily split at random.

‘Disability getting worse’

In some of the treatment summaries we report on the effect of MS treatments on disability, specifically, ‘disability getting worse’. This refers to an increase in disability (by at least one point on the EDSS) that lasts for at least three to six months.

Expanded Disability Status Scale (EDSS)

The Expanded Disability Status Scale (EDSS) is the most widely used disability measure in clinical trials of MS. It is based on the results of a neurological examination and the patient’s ability to walk. Scores range from 0 (no neurological abnormality) to 10 (death from MS). Specifically, EDSS steps 1 to 4.5 include people who can walk without an aid, but have a level of impairment in what is known as a functional system (FS), such as limb strength, coordination, sensation, bladder & bowel function and mental functions. EDSS steps 5 to 9 are based on the level of impairment to walking.

Flu-like symptoms

‘Flu-like symptoms’ is a term that is often used to describe the side effects of interferons. It can include fever, chills, cough, sore throat and body aches and pains. In the case of interferons, these symptoms tend to be short-term, happening immediately, and for several hours, after the injection. They are most common, and typically most severe, during the first few months of treatment.

Hyperbaric oxygen therapy (HBOT)

Hyperbaric oxygen therapy (HBOT) involves breathing pure oxygen in a specially designed, pressurised chamber. It gained popularity as a treatment for MS in the 1980s. HBOT is typically delivered over multiple sessions (20 sessions within a month), lasting for up to 90 minutes and may involve top up sessions after this time.

Interferons (Avonex®, Betaferon®, Rebif®)

Interferons are proteins produced naturally in the human body to help fight infections and regulate the immune system . Interferons have been shown to be partially effective in reducing the risk of relapses in MS and slowing the progression of disability. They are considered a ‘first line’ treatment of MS and are commonly prescribed for people with relapsing-remitting forms of MS.

There are three interferon treatments available in Australia that are covered under the Pharmaceutical Benefits Scheme (PBS).

  • Avonex® — given by intramuscular injection weekly
  • Rebif® — given by injection into the skin three times a week
  • Betaferon® — given by injection into the skin on alternate days
Long-term follow up studies

Long-term follow up studies are used to understand the effects and side effects of treatments over many years. This type of study is particularly important in MS because it is a condition that often progresses over 30 to 40 years and some drugs are taken for many years. RCTs, whilst considered the highest quality type of study, may only last for 2 or 3 years.

Long-term follow up studies are called ‘observational’ studies. The researchers simply observe what happens to people once the original RCT finishes. The results of observational studies are not considered as certain as the results of RCTs but they do provide some longer-term information. Talk to your health professional or your local MS Australia office to find out more about the results of these longer-term studies for MS treatments.

Multidisciplinary rehabilitation

Multidisciplinary rehabilitation refers to a therapy program that aims to reduce symptoms, increase independence and maximise participation in society. It is coordinated by a specialist doctor and delivered by a team of different therapists. These could include nurses, physiotherapists, occupational therapists, speech pathologists, orthotists, dieticians, social workers, counsellors, psychologists and neuropsychologists. Multidisciplinary rehabilitation can be conducted in hospitals, community centres and /or in the home.

The amount and type of therapy is highly variable. It is usually tailored the individual’s specific needs and goals. Rehabilitation can address things related to mobility, personal care, pain, speech and swallowing issues and problems with thinking and memory. Some programs last only a few days or weeks, whereas other programs may be once a week for a year.

Multiple Sclerosis (MS)

MS is a disease of the central nervous system which results in damage to myelin — a protective sheath surrounding the nerve fibres. When myelin is damaged this interferes with messages between the brain and other parts of the body. The symptoms of MS are different for each person. For some people, MS is characterised by periods of relapse and remission while for others it has a progressive pattern. For everyone it makes life unpredictable.

Taken from: Understanding MS : An introduction for people living with MS, Sydney, NSW, MS Australia 2012

Observational study

In an observational study, or long term follow up study, researchers simply observe what happens to people. In Phase IV clinical trials (another kind of observational study), the researchers observe what happens to people once the RCT ends.

The results of observational studies are not considered as certain as the results of RCTs. For this reason they are not usually included in Cochrane systematic reviews. But they do provide some idea about the longer–term effects of MS treatments.

For example, RCTs about MS drugs usually only last for a few years. Yet MS is a condition that can affect people for 30 or 40 years. To understand the effects and side effects of treatments over many years, researchers and health professionals will rely on long term follow up studies.

Talk to your health professional, MS nurse or your local MS Australia office to find out more about the results of these longer term studies for MS treatments.

Pharmaceutical Benefits Scheme (PBS)

The Pharmaceutical Benefits Scheme (PBS) is the way in which the Australian Government subsidises the cost of medicines. The PBS Schedule (searchable online) lists the medicines that are available to Medicare-card holders at a subsidised price. Most of the listed medicines are dispensed by pharmacists, and used by patients at home.

Phases of clinical trials

Clinical trials are conducted in ‘phases’. Each phase has a different purpose and helps researchers answer different questions.

  • Phase I trials — Researchers test an experimental treatment in a small group of people (20-80) for the first time. The purpose is to assess its safety and identify side effects
  • Phase II trials — The experimental treatment is given to a larger group of people (30-100) to assess how effective it is and look at its safety in more detail
  • Phase III trials — The experimental treatment is given to large groups of people (1,000-3,000) to confirm how effective it is, monitor side effects, compare it with standard treatments, and collect extra information to allow it to be used safely
  • Phase IV trials — Once the treatment has been approved and is made available to the public, researchers track its safety and effectiveness over time. This is a type of observational study.

Adapted from: National Institutes of Health “NIH clinical research trials and you”

Placebo

In health research, new treatments are often tested against a placebo (sham or dummy treatment). The placebo is designed to be undetectable to research participants from the treatment being tested yet it has no effect. Research participants receiving a placebo are often called the control group.

Primary Progressive Multiple Sclerosis (PPMS)

Some people diagnosed with MS will not experience clearly defined relapses. This is usually described as PPMS. People with PPMS represent about 10 per cent of all those with MS. The main feature of PPMS is a constant pattern of symptoms from the time of diagnosis. There may be periods where symptoms are stable or even improve, but overall loss of function tends to increase.

Taken from: Understanding MS : An introduction for people living with MS, Sydney, NSW, MS Australia 2012

Progressive relapsing MS

PRMS is defined as progressive disease from onset, with clear acute relapses (with or without recovery) with periods between relapses characterised by continuing progression.

Taken from: Understanding MS : An introduction for people living with MS, Sydney, NSW, MS Australia 2012

Randomised controlled trial (RCT)

To test whether a treatment works, the preferred type of study is a randomised controlled trial (RCT). In the case of MS, this would involve a group of people with MS being split into two groups at random. One group gets the treatment being tested (for example, the drug Tysabri®) and the other group gets something different. This group is called the control group. The control group might get a different drug, a dummy drug (placebo) or no treatment at all. Researchers then compare the results between the two groups. Sometimes you may see terms like “single blind” and “double blind” RCTs. This refers to whether or not the researchers and the participants know the details of the treatment.

But relying on the results of just one study may not necessarily provide an accurate picture.

Take, for example, the case of hyperbaric oxygen therapy (HBOT) in MS. Hyperbaric oxygen therapy involves breathing in pure oxygen in a pressurised chamber. An RCT conducted in 1990 showed that hyperbaric oxygen therapy was beneficial for people with MS (Oriani et al 1990). Yet a different RCT conducted in 1987 showed that it had no effect in people with MS (Barnes et al 1987). So how can we tell if it works? This is where a systematic review is helpful.

Relapse

Relapses (also called exacerbations, attacks, flare–ups or episodes) are periods when new symptoms appear or existing ones get worse and remission is when they improve. Relapses are changes in old symptoms or the appearance of new symptoms which last more than 24 hours. Some relapses resolve quite quickly, while others can take weeks or months to subside. Many relapses will fully resolve, while others may have an impact on long–term function.

Taken from: Understanding MS : An introduction for people living with MS, Sydney, NSW, MS Australia 2012

Relapsing Remitting Multiple Sclerosis (RRMS)

The majority of people with MS (approximately 85 per cent) are initially diagnosed with RRMS. The main feature of RRMS is the fluctuation in symptoms. Relapses (also called exacerbations, attacks, flare-ups or episodes) are periods when new symptoms appear or existing ones get worse and remission is when they improve. Relapses are changes in old symptoms or the appearance of new symptoms which last more than 24 hours. Some relapses resolve quite quickly, while others can take weeks or months to subside. Many relapses will fully resolve, while others may have an impact on long-term function.

Taken from: Understanding MS : An introduction for people living with MS, Sydney, NSW, MS Australia 2012

Secondary Progressive Multiple Sclerosis (SPMS)

Over time, most people who have RRMS will find they have fewer relapses. At this time, their disease may be categorised as SPMS. After 25 years a portion of people initially diagnosed with RRMS will be described as having SPMS. Some people with a SPMS pattern of disease will still have relapses, others will not. The main feature of SPMS is a more constant pattern of symptoms.

Taken from: Understanding MS : An introduction for people living with MS, Sydney, NSW, MS Australia 2012

Statistical Significance

Tests of statistical significance show whether the effect of the MS treatment in the sample of people with MS is due to chance, or whether the treatment had a real effect. It doesn’t tell us if the treatment had a large or small effect, but if a result is statistically significant it suggests the effect is real.

Systematic review

A systematic review is a report that sums up the best available research on a particular topic. This allows the results from a number of studies to be pooled together. The authors follow careful procedures and look at the strength of the evidence to make informed conclusions about the overall findings. Systematic reviews help us to decide if treatments work and whether any more research needs to be done. Systematic reviews of multiple studies are generally considered more convincing than just looking at the results of single studies alone.

To learn more about the systematic reviews visit

In the case of the hyperbaric oxygen example outlined under randomised controlled trial, the authors would ideally search for and summarise all the RCTs that have investigated whether or not hyperbaric oxygen therapy is beneficial for people with MS.

In 2004, researchers at the Cochrane Collaboration did just that. They found nine RCTs in total. When considered all together, the results showed that there was no consistent evidence that HBOT is beneficial for people with MS (Bennett and Heard 2004). The authors of the review concluded that no further studies should be done in the area.

The Cochrane Collaboration

The Cochrane Collaboration is an international, non–profit organisation that produces systematic reviews about health care treatments. To read more about Cochrane Collaboration, visit the FAQ page.

Therapeutic Goods Administration (TGA)

The Therapeutic Goods Administration (TGA) is Australia’s regulatory authority for therapeutic goods, including medicines and medical devices such as wheelchairs. They carry out assessments and monitoring activities to ensure therapeutic goods available in Australia are of an acceptable standard. The TGA maintains the Australian Register of Therapeutic Goods (ARTG). The ARTG lists all medicines that are authorised for use in Australia (including those for MS) and outlines their specific indications for use.