Related Posts
Why do clinical trials?
Over the past couple of years, clinical trials are coming on line for people with Gorlin Syndrome. Clinical trials are usually used to test new treatments (for example, patidegib) or older treatments that are being tried for the first time in Gorlin Syndrome (for example itraconazole). The information here offers some guidance for people thinking about trials.
Positive results from trials are required before a drug can be ‘licenced’. Up to now, drug licensing has been done by European Medicines Agency (or the Food and Drug Administration in the US). Trial results are also studied by organisations that evaluate value for money, for example NICE in the UK. Doctors will evaluate trial results before recommending drugs.
Of course, most importantly, people with Gorlin Syndrome will also want to know a bit more about trials. This is important if you’re thinking about going into a trial or if you want to start a new treatment.
What information do we get from clinical trials?
• Trials can confirm whether or not the drug works (in the case of Gorlin syndrome it could work at treating BCCs some a person already has or prevent future BCCs from coming along.
• Confirm whether or not the drug also meets the individual’s personal needs. For example, the trial could confirm that the drug enables an individual to attend school or go to work more often, that they can enjoy day to day activities or simply that they feel happier. These are sometimes called Health Related Quality of Life or Patients Related Outcome Measures (PROMs).
• See how often side effects happen. This is most successful for trials that include many people and take place over a long period because some side effects only happen occasionally or after a long time on treatment.
• See how well a drug is ‘tolerated’. This means – how convenient is a drug to use. For example, if a drug is a cream applied to the face – it won’t be use if you can’t apply sunscreen on top of it, and If a treatment causes distress: pain, nausea, unsightly inflammation then people are unwilling to continue to use it. Drugs which have to be given in hospital are obviously much less convenient than drugs which you can use at home.
• Work out how much the drug will cost to meet these aims. this is called Health Economics. This is obviously affected by the price of the drug. However, it is also affected by how well a drug works. If a drug works really well in 100% of people, it effectively costs less to achieve its aim than a drug which only works a bit, in only 50% of people. It was for this kind of reason that vismodegib (Erivedge) worked out to be too expensive to be approved by NICE in the UK.
How are clinical trials done?
Clinical trials must be carefully designed and include several different components. Various types of trials have been done, but over the last 30 years or so it has become clear that the best trials are Double Blinded Controlled Randomised Clinical Trials (RCTs)
RCTs are designed to take all the chance out of trials and to stop the trial team from ‘cheating’. A trial team may deliberately cheat because they want to make money from the new drug. But, more often, they can subconsciously cheat because they want the treatment, they have spent their lives developing to work. RCTs can prevent this from happening.
Researchers planning a new trial will have to get permission from a Research Ethics Committee. Once this permission has been given, the research team can start selecting people to invite into the trial. The team will use inclusion and exclusion criteria to work out who they can invite.
If you are invited and you decide to join, you’ll be asked to give informed consent before anything else can happen. Next, you’ll be randomised to either the new drug or a control. RCTs compare the new drug with a control – either a placebo or an existing drug. Neither the trial participant nor the researcher will know who is on which, whilst the trial is running. Each of these steps and features is described in the next sections.
Double – blinded trial
Neither the person in the trial or the trial team can know who is on which. Otherwise, it would be possible for the trial team to cheat and change the results so that the group receiving the new treatment do better. In a single blinded trial, the reserach team knows who is on what.
Controlled trial
The new drug has to be compared to something. Often, it can be compared to an existing treatment which is widely available. Sometimes, there is no existing treatment available and in this case the trial has to be compared to a placebo. For example, because there are no drugs designed for people with Gorlin Syndrome, most of the trials coming on line now use placebos. (A Placebo – this is a substance that looks and feels like the drug being tested, but does not contain the active ingredient, for example, it may be a sugar pill.)
Uncontrolled trials consist of simply giving a few patients the new treatment. Uncontrolled trials are not helpful because they do not compare improvements in BCCs that would have taken place any way.
Randomisation
The people taking part in the study have to be divided up at random, as to who gets the active treatment and who gets the standard treatment or the placebo. This has to be done at random because otherwise it would be possible for the team to cheat and put all the people on the they think will get better in the treatment group.
Inclusion & exclusion criteria
Inclusion criteria define who can join a trial. For example – ‘people with confirmed Gorlin Syndrome’. Usually they will also state how active your Gorlin Syndrome i,s for example that you must have had 10 BCCs over a two year period. In general, trials need people with active disease.
On the other hand, exclusion criteria define who can’t join the trial. Sometimes these are obvious, for example women of child bearing age not using contraception are often excluded from a trial, to reduce the risk to an unborn baby. Sometimes the criteria are subtler, for example excluding people with mental illness. This would be a real problem for Gorlin Syndrome because about half of us have a history of depression or anxiety.
Informed consent
When you have any treatment, you should be asked to give informed consent. Often this is given verbally, for example if you have a urinary infection and your GP recommends antibiotics, the GP should check with you that you agree. The GP should tell you what the common side effects are. Most of us are used to signing consent forms when we go for operations, confirming we understand what the intended benefits and potential risks are. The same applies for any treatment which has not been thoroughly investigated – it should only start after informed consent has been given. The same is true for clinical trials.
Usually, clinical trials will invite you to give informed consent after talking to your specialist doctors, reading some material and after being given some time to consider whether you really want to join the trial. It should also be clear that you can withdraw the consent at any time you choose, without giving a reason and without this affecting your regular treatment.
Ethics Committee.
Ethics Committees are committees run by hospitals which oversee clinical trials. They include doctors and nurses, but also lay people. A trial can only go ahead if the Ethics Committee approves. In the US, Research Ethics Committees are sometimes called Institutional Review Boards.
I want to make the best possible choices? How will looking at trials help me?
There are a few things you can consider. Double Blinded Controlled Randomised Clinical Trials provide the best evidence of how effective a treatment is. Trials that are not controlled or not blinded are inferior and, many doctors would argue, should not be used to state how safe or effective a treatment is.
The best trials are also conducted at several different centres at once – so called multi centre trials. The more trials the better, especially if they have been conducted by different groups in different places. Sometimes, data various trials can be combined in a meta analysis, which gives a very powerful way of measuring how effective a treatment is.
It is also helpful to look at which patients recruited to a trial. For example, the data from a trial which was done in people who had only ever had a single BCC may not apply fully to people with Gorlin Syndrome. And most trials are done in adults – and so the information gained from the trial may not apply to children.
I’ve heard of a new treatment, but there is no information on it from clinical trials. Why is this?
Most treatments used for BCCs in Gorlin Syndrome have been through clinical trails . For example, imiquimod, 5 -fluorouracil, and several forms of PDT have been through good trials. The newer hedgehog inhibitors (vismodegib, sonidegib, patidegib, itraconazole) are either going through trials or have been trialled.
There are a few reasons a treatment may be available even if no trial data are available.
Old treatments were not always tested in the same way as modern treatments are. For example, most types of surgical treatment have been around for a long time. We know how effective and what the side effects are through long experience. This applies to the different types of treatments when the BCC is cut out from the skin.
Sometimes a trial was done but the drug was found to be unsuccessful. These results are obviously very important. However, sometimes the pharmaceutical company will not publish negative results. This is a good reason to avoid any treatment where there are no good trials to support it.
Some treatments are described by the manufacturers as nutritional supplements. In many countries nutritional supplements do not need to have been through a clinical trial. However, any nutritional supplement that claims to benefit BCCs should have been through a proper trial. If it has not been through a trial, you are risking taking something that may not work or could do you harm.