Life's a trial

When I'm doing research roundups, I quite often talk about clinical trials being "Phase 2" or "Phase 3". But what do these terms mean? The development of a new drug or other intervention is a long-term process. commonly taking 12 or more years before being available to patients. The regulatory process adds another hefty chunk of time.What's happening for it all to take so long?

Research begins in the laboratory, where potential treatments are tested on animals: for instance, there is a strain of mice which have a condition very like MS. Testing drugs on them gives a reasonable idea of whether they're likely to help people with MS. Around 1000 potential drugs are tested for each one that makes it to clinical trials.

The use of animals in drug trials is a whole other question, one I might discuss in a future blog post. If the drug is helpful for the animals (and how that's worked out is again a subject for a future blog post), the researchers will look for more funding to test it out on people, in clinical trials. The clinical trial process has four phases.

Phase 0 Very low doses of the drug are given to 10-15 people to see whether the drug does what was expected in humans. Tests are carried out to check what the drug does to the body, and what the body does to the drug.

Phase I The drug is tested on usually 20-100 healthy volunteers, to check that it is safe. These volunteers are normally paid, as they won't get any health benefit from participating, and are taking the risk of being given an untested drug. Some of you may remember news coverage of a Phase 1 trial in 2006 where 6 healthy volunteers became violently ill after taking a new drug.

Phase II Designed to assess how well the drug works, and what is the best dosage. Between 100 and 300 volunteer patients take either the drug or something else - the existing treatment if there is one, or a placebo.

Phase III The drug is tested on a large number of patients over a number of sites. This phase aims to be the definitive assessment of how effective the drug is, compared with any current treatments. Sometimes a manufacturer wants to prove that their drug works for other patients or other conditions than those originally established. In that case the Phase 2 or 3 trial would be the first stage.

Phase IV This is the period of surveillance once the drug is on the market. Safety continues to be checked, and technical support is available.

Clinical trials can take a long time to run. It can be difficult to recruit the number of people needed, particularly in Phase III. For many long-term conditions, it can take several months to see any effect from the drug. I recently participated in a Phase II trial for a full year.

Most Phase III trials (and some Phase II) are randomised, double-blind and controlled.

• Randomised means that participants are randomly assigned to the treatment or placebo groups
• Double-blind means that neither the participant nor the researchers know whether they're receiving the treatment or the placebo. It's important that the researchers don't know, as they might subconsciously behave differently to people in the two groups.
• Controlled means that one group receives a placebo (or the existing treatment, if there is one).This means that the effect of the new drug can be isolated. Is it better than the existing treatment? If so, how much better?
• Some trials are designed to cross-over, This means that halfway through the trial period, the participants swap over to receiving the other treatment. Those who were gettng the active drug will change onto the placebo, and vice versa.

After the trial process, the manufacturer will apply for the drug to be licensed, which has to be done separately in different parts of the globe.Here in the UK, once it's been licensed, the action then moves to an agency called NICE, who decide whether the NHS should fund treatments.

Their decisions are based on cost-effectiveness, potentially leading to some controversial outcomes. Recently they've refused funding to the new MS drug Gilenya, and there have been several decisions where funding has been refused for expensive cancer drugs which were likely to give only a few more months of life.

In some cases, local Primary Care Trusts still have to agree to fund the treatment. There have been problems recently with Sativex, which is licensed for use in MS spasticity if other treatments don't help. Many PCTs are refusing to fund it. The MS Society is campaigning on this: if you have funding for Sativex refused, they provide advice on what steps to take.

You're most likely to find out about trials through your consultant. If you'd be interested in participating in a research project (without commiting yourself to anything!) let them know.

It can't be denied that there are some risks involved, as there are with any treatment. But I found trial participation interesting, and if the drug concerned goes on to be approved I'll feel quite proud: I was part of that!

MS research roundup February 2012

With apologies for the long gap since the last one - here, finally, is my latest research roundup. And there's some real goodies this time!

MS is conventionally seen as an auto-immune condition. For some reason, not yet fully understood, the body's immune system begins to attack the myelin sheath surrounding the nerves. This has recently been challenged by the CCSVI theory, which states that MS is caused by blockages in the veins of the neck leading to back-up of blood and consequent deposition of iron in the brain.

Now an American researcher has developed a new theory. She believes that MS is a metabolic disease, caused by the body having problems dealing with fats in the diet. The rise in the number of cases over the last few decades is due to us, as a population, moving to a diet high in carbohydrates and saturated fats. Oxidised LDL cholesterol accumulates on nerve cells and triggers an immune response, leading to scarring of the cells. Men and women metabolise fats differently, which could account for the higher prevalence of MS in women.

It's an interesting theory, but obviously needs much research done to see if it holds water. Watch this space..

I've talked about vitamin D several times before: there's a lot of research going on in the field, and there seem to be many links between vitamin D and MS. Vitamin D is created in the body following exposure to sunlight, so people tend to be more at risk of deficiencies the further they are from the equator.

An international group of researchers are now suggesting that vitamin D should be added to foods like milk and fruit juice in Scotland, which has some of the highest levels of MS in the world. The Scottish Parliament is unconvinced. Food supplementation already exists: iodine is added to table salt to protect against goitre. Should vitamin D be added to the list?

As many of us know all too well, MS can be difficult and time-consuming to diagnose. This can cause distressing uncertainty, as well as delays in commencing treatments. Israeli researchers have developed an electronic "nose" which can diagnose MS, as well as some cancers, from a person's breath. They identified organic compounds in the breath that are a sign of MS, then produced sensors to detect them. They hope that their device will allow MS to be diagnosed at an early stage and without using invasive techniques like lumbar punctures. Still early stages for this research, but a very exciting development!

On to treatments. At least 80% of people using interferon-b eventually develop antibodies to it, meaning treatment has to be stopped. Instead, German researchers tried injecting mice with an MS-like disease with a type of RNA which stimulates the body to produce its own interferon-b. The results were excellent. This could prove to be an excellent way round the antibody problem.

As people with MS age, the rate of remyelination of nerve fibres slows, resulting in the loss of more nerves. A research group in the UK have managed to reverse this decline in mice by exposing them to stem cells from young mice. Stem cells show great promise in remyelination, and this is a great discovery.

Finally, research on treatments for MS symptoms.

The MS International Federation have released the results of a survey on fatigue. 86% of those who responded said that fatigue was one of their main symptoms, and 46% that fatigue has a high impact on their lives. For those of us with MS fatigue, this will come as little surprise. Interesting data, showing how important it is for healthcare providers to recognise the problem of fatigue. Important to remember, though, that those who responded had chosen to participate in a survey on fatigue, and might therefore be those for whom it's an important consideration. People unaffected by fatigue might not have been interested in participating.

An Israeli research group did a trial involving three groups of patients. One group received electrical stimulation of the left prefrontal cortex, one of the motor cortex, and the final, control, group received a sham stimulation. After 18 treatments, the group receiving stimulation in the motor cortex had less fatigue and less depression. There was a tendency towards less fatigue in the prefrontal cortex group. The control group had no signnificant improvement. Further research is planned to investigate the effect of the stimulation on metabolic and neural activity.

Many of us with MS also experience cognitive problems - short term memory loss, lack of concentration, and so on. Italian researchers used computer-based rehabilitation programmes to help with attention and information processing. One programme, for instance, is a train driving simulation: you have to observe the control panel of the train and the surrounding countryside while encountering increasingly difficult distractions. After a 12-week programme of treatment, patients had improved attention and information processing skills, although no changes were seen on MRI. It seems training can help, but it's no cure.

I hope you agree that there were some really promising bits of research this time. Let's see what happens next!

Back on the chain gang: the WRAG and #workfare

There's been a lot of indignation on the internet this week.It was partly down to an error by Tesco, who advertised a "work experience" job as if it was a normal vacancy, but paying only Jobseeker's Allowance plus expenses. I have no doubt that their advertising mistake was genuine, but it highlighted the practice of big companies increasing their already huge profits by using taxpayer-funded labour.

This type of social welfare system is known as workfare. Under the system that previously operated in the UK, receiving benefits was conditional on things like searching for work and being available for work. Under workfare, you are expected to undertake training, work experience or community work. If you do not complete these satisfactorily, your benefits are reduced.

Workfare became a political headline-grabber in the UK about a month ago, after geology graduate Cait Reilly refused to take up a placement at Poundland, because it was unpaid: she argues that young people need jobs, not fake "work experience" schemes.

Now, the latest. The Guardian has received documents revealing secret DWP plans. If you're on Employment and Support Allowance (ESA), in the Work Related Activity Group (WRAG), it's been decided that you might be able to work at some time in the future. The documents reveal that those in the WRAG, too, may be placed on workfare, even though it's acknowledged that at that point in time they are not fit for work. For some of us, fitness to work may be years or decades away, while others of us will never be fit for work.

So, will we be forced out to work when we're not fit? Forced back to the chain gang?

Well, many issues have been raised about the policy since the Guardian's story. Here are a few thoughts of my own.I'll talk about "I", though I've not been transferred onto ESA yet.

• Suppose I agree to take part in a workfare scheme. What happens if (when) I'm not well enough to go? What happens if I arrive late, or have to leave early, due to my disability? Or have a medical appointment? After all, the DWP have acknowledged I'm sick and/or disabled by putting me in the WRAG in the first place.
• My doctors may have said it would be dangerous to my health to work. Where do I stand? (Or, more probably, sit)
• According to the Guardian documents, the "host employers" have to make "reasonable adjustments", as with the Disability Discrimination Act. Is this really likely if I'm only there for a few weeks? Funding under Access to Work is no longer available, having been withdrawn by this government.
• The Health & Safety at Work Act is still in force, and protects me, all other employees, and any members of the public visiting the workplace. Could be expensive for the "host employer" if anything goes wrong.
• The Employers' Liability Act also applies. As long as I'm certified as "not fit for work" by my doctor, I will not be covered by an employer's insurance.

At the time of writing, several large companies have dropped out of the workfare scheme for people on JSA, including Waterstones, Sainsbury's, TK Maxx, and Matalan. Hopefully workfare for people in the WRAG will be quietly dropped before the government shows itself up yet again.

Reply to email to my MP re the #WRB (with comments)

I emailed my MP, James Clappison, with some of my concerns about the Welfare Reform Bill. I'm going to copy out his response below, with some comments by me in brackets. It's long, and addresses both the points I raised and some I didn't. I therefore believe it to be a form letter. Mr Clappison is a Conservative.

Dear Ms Milne,

Thank you for contacting me about the Welfare Reform Bill.

 I believe the bill makes the tough decisions that will restore fairness to the benefits system, support the vulnerable and provide the right incentives and support for people to find work. This is why the Government overturned the amendments that the House of Lords made. Having read your concerns about the legislation, I would like to take this opportunity to reassure you about aspects of the Bill which you have raised.

(Oh, so they didn't oppose the Lords' amendments because they had financial implications then? Well just fancy that!)

The one year time limit on the length of time that people can receive contribution-based Employment & Support Allowance (ESA) is an important measure designed to ensure that people make the journey back towards work. It strikes the right balance between restricting access to contributory benefits and allowing those with longer-term illnesses to adjust to their health condition and surrounding circumstances, and it is double the time allowed for contribution based JobSeeker's Allowance in recognition of that fact. The one year time limit is not an arbitrary time limit. It is in line with similar limits in other countries around the world including France, Spain and Ireland. It should also be noted that it is only the contributory element of ESA that will be time-limited, not income-related ESA.

(You could double, triple, or multipy by ten the JSA time limit. Many with sickness and disability would still not be fit for work. The Government's own figures show that people with learning difficulties, for instance, take over 2 years to gain employment. Those of us with progressive conditions know that if we're not fit for work now, we never will be again.)

Members of the House of Lords also rejected Government plans to remove the automatic qualification that children with disabilities receive to contribution-based Employment & Support Allowance 'Youth'. However, this change was not made with the intention to reduce the support available to children with disabilities when they progress to adulthood.

The three principal reasons why the Government has instituted this change is because it simplifies the benefit system by abolishing a category where the majority of claimants would be entitled to income-related ESA. This is paid at the same or a higher rate for many people. Second, this measure aligns the treatment of ESA 'Youth' with other groups claiming contributory ESA to create a consistent system in the run up to the introduction of Universal Credit. Third, entitlement to income-related ESA will help ensure those recipients automatically qualify for passported benefits, such as free NHS prescription charges, instead of having to make a separate claim.

(Now, it's entirely possible I've misunderstood this second paragraph completely. But it seems to me they're saying income-related when they mean contributory, and vice versa. And, of course, these individuals won't be entitled to income-related ESA, to passport them to things like free prescriptions, if they're still living with their parents, or with a partner who's earning. They'll have no income of their own at all.)

One of the other measures that Peers voted on was a proposal to exempt cancer patients from any time limit on contribution-based ESA, which is unnecessary as the vast majority of cancer patients would be placed in the ESA support group and or choose to be in work.

(With recent decisions including a man in a coma being found fit for work (due to a clerical error), and a terminally ill man with dementia being called to a Return To Work interview, I wouldn't be so sure.)

The evidence put forward by various oncologists and other experts shows that for some people, being able to continue working or getting back into work after diagnosis is an important part of the recovery process. People should not be confined six months out of work if that is not appropriate for them. Similarly, there is also a need for some patients to have full financial assistance at what is a very difficult time for them and their families. In those cases, the Government has been quite clear, people shall continue to receive all the help that they need. You should also be aware that the Government's changes to the criteria for the support group mean that more people will be able to access the support because the (sic) certain treatments, including oral and chemo-irradiation therapies are now recognised.

(I know that for some people work is an important part of their recovery. For some, not all. And I don't believe that anyone is suggesting sick leave should be compulsory, except in the rare situations where healthcare professionals believe that returning to the workplace could cause danger to yourself or others.)

I realise you are concerned by the Government's proposal to place a cap of £26,000 on the amount of benefits that a workless household can receive but I believe that the cap has been set at an appropriate level. It is right to include Child Benefit in the cap disappointed by the decision in the House of Lords to exempt Child Benefit (sic). This is because the cap would be set so high that it would become meaningless as well as undermining the key principles of fairness that our welfare system is based on.

There has to be a limit on the amount of money benefit claimants can receive and Minimsters believe that the limit is currently set at a fair rate of £26,000, which it is worth noting, is the equivalent to someone earning £35,000 before tax. This is a salary that many working families would be happy to receive and underlines the point that hard working people should not pay their taxes in order to support people who refuse to work.

(The benefit cap has received much of the media attention over the WRB, in spite of affecting far fewer households than other provisions of the Bill. Those it does affect mostly live in central London, with the bulk of the benefit concerned being paid to rapacious landlords. The figures quoted are not comparing like with like: another example of Government misdirection. This excellent post by Declan Gaffney explains in detail. And "people who refuse to work"? Again, the government pushes its "scrounger" rhetoric. Over half the households which will be affected by the benefits cap contain at least one disabled member. And in the current economic climate, to be jobless most certainly doesn't mean you "refuse" to work!)

With regard to the under occupation of social housing, I believe that when there are 250,000 social housing tenants living in overcrowded accommodation and over 5 million people on social housing waiting lists, it is unacceptable for the Government to subsidise people to live in accommodation that is too big for their actual needs. Many ordinary people are not in a financial position to be able to afford to have a spare room. There is also a fundamental misallocation of resources in that there are over 1 million spre rooms that are paid for by the taxpayer.

(Wow. If only there was more social housing. If only some Government hadn't sold it all off and banned councils from using the proceeds to build more social housing. Uh, what Government was that again? By the way, we don't seem to know yet what'll happen about disabled people who need a second bedroom for equipment storage, or to allow a carer to sleep over.)

I know that the issue of charging has alarmed people but it should be recognised that this is a principle that all parties support and was originally set out in Sir David Henshaw's review of the CSA in 2006. The charge itself will act as an incentive for parents to establish their own arrangement. The £100 charge will cover only a proportion of the costs of an application and those on out of work benefits will pay only a (sic) £50 with an upfront charge of £20.

It should also be noted that 50 per cent families (sic) believe that with the right support, they could develop their own arrangements. The Government is spending £20 million improving support to families at this stage and it should also be noted that some people will be exempted from charges if for example, they are the victim of domestic violence.

(Only £50. Only. There speaks someone who's never been on benefits. And frankly, I don't care if this policy is supported by the Dalai Lama. I believe it's discriminatory.)

I hope this clarifies why the Government is making the changes that it is and that it reassures you that this will not undermine the support available to the disabled and people who genuinely need support.

(Well, frankly, no. And calling us "the disabled" doesn't help.)

Thank you again for taking the time to contact me.

(My pleasure)

Yours sincerely

(Love and kisses)

James Clappison

(Margo xx)

Defining doctoring

The General Medical Council wants to find out what is good medical practice today, and what makes a good doctor. They ran debate and discussion throughout 2011, and now they're having a public consultation.

They want to hear from everyone - doctors, organisations, and members of the public.There are separate online questionnaires for each, and you can type in comments as well as ticking boxes.

One subject they ask about is whether doctors should be encouraging patients to return to (or take up) work - interesting in view of the current welfare reforms!

All the links you'll need are here. The consultation closes on 10th February.

Please do take part. This is an important subject, that will affect us all.