Wednesday, 12 March 2014

My Tomorrows...for access to investigational new cancer drugs

New promising cancer therapies and how to get early access

Diagnosed with a fatal illness for which mainstream medicine has no answer, you will face the ultimate challenge of simply accepting the status quo or battling with family, physicians, and / or others in search of an alternative therapy that will potentially give you a fighting chance of survival. As mentioned in an earlier blog, there are some really promising therapies either in pre-clinical studies or early phase clinical trials. However, when you don’t have the luxury of time, waiting for next generation treatments becoming available is simply not an option.

 Image courtesy of Baitong333 -  Free Digital Photos
Thankfully, when new therapies (that will be used to treat fatal diseases) show encouraging results in the earliest stages of clinical trials, they can be made available before they are approved (such as the 5T4 based immunotherapies I discussed in my previous blog). This availability, however, is subject to strict conditions and regulations that will need to be adhered to in order to bypass the regular new drug marketing authorisation process which essentially depends on positive outcomes of Phase I – III clinical trials (a process that can take 5 – 10 years to be completed).

New cancer drugs and compassionate use programmes

For info about Biozantium by Paeon Laboratories:
Early Access and permission to use new (not yet approved) drugs through programmes such as Named Patient Use (EU), Single Patient Program (USA), Compassionate Use (EU) or the equivalent Expanded Access Program (USA) depend on successful applications submitted to the various regulatory authorities in your country. Luckily, you and your doctor may not have to face this struggle of applying to the authorities alone.  Recently a new private organisation called My Tomorrows was founded. They essentially act as a link between the manufacturer and the prospective user by facilitating and coordinating requests for compassionate use to the regulatory authorities.

Please note though, that there are potential risks as well as potential benefits when you decide to request access to therapies that have not yet been approved by regulatory authorities. There are a number of risks (some bigger than others). The fact that early access is only allowed in cases where “first in human” trials have been conducted means that perhaps as little as tens of people may have used the drug. Therefore it is likely that not all side effects are known at that point (i.e. efficacious and safe dosage is not yet completely determined at that stage). Essentially what this means is that your doctor may unknowingly treat you with a dosage that is too high or too low or that the therapy simply does not work in your case. Thus it will be incredibly important to consider the potential gain versus the potential risk very carefully with your physician before you embark on such a venture.

Clinical trials for terminal cancer patients

As mentioned earlier, another way of gaining access to new therapies or drugs is through enrolling in clinical trials (click here for clinical trial database in EU or USA and worldwide). However, clinical trials usually have very strict selection criteria and pre-determined numbers of subjects that will be allowed to enter the trial. Once that pre-determined number has been reached the trial will no longer recruit patients. Also, the vast majority of patients are unlikely to gain access to phase I or phase II clinical trials for the simple reason that phase I trials only recruit tens of people while phase II trials only recruit hundreds of people (there are far more patients than there are places in clinical trials). Phase III trials usually recruit thousands of people. However, phase III clinical studies are placebo controlled type of trials which means that you may end up not getting the new investigational drug (although for ethical reasons you would be given the standard treatment at the minimum in the case of cancer).

For clarity I will briefly describe the 4 types of clinical trials.

  1. Phase I – This is the first time a new drug / medicine is tested in humans. During a phase I trial the investigator is concerned with the safety of the drug. At this point the investigator is not looking at the effect the medicine may have on your disease. More precisely, the principal goal of a phase I study is to establish the recommended dose and / or schedule of an experimental drug or drug combination for efficacy testing in a phase II trial. A phase I trial design consists of many elements, including starting dose, dose increment, dose escalation method, number of patients per dose level, specification of dose-limiting toxicity, target toxicity level, definition of the maximum tolerated dose (MTD) and recommended dose for phase II trials, patient selection, including the number of participating centers. Even though phase I studies are primarily concerned with toxicity and safety, the guiding principle for dose escalation in phase I trials is to avoid unnecessary exposure of patients to sub- therapeutic doses of an agent. As such, most sponsors and investigators will want to treat as many patients as possible within the therapeutic dose range. The dose escalation methods that are employed within phase I cancer clinical trials fall into two broad classes: rule-based designs, which include the traditional 3+3 design and its variations model-based designs.
  2. Phase II - Not all therapies that are tested in a phase I trial make it to a phase II. Phase II trials attempt to demonstrate efficacy of a new investigational drug / medicine in a relative small group of people (up to 200 patients). These trials may be for patients who all have the same type of cancer, or who have several different types of cancer. In phase II trials major toxic reactions in humans are generally not expected while the treatment has been proven effective and safe in animals. However, phase II trials can sometimes extend some of the objectives of a phase I trial, in order to apply these to a larger patient population. Importantly, phase II studies generally do not make use of a placebo control group (i.e. all study participants receive the new investigational product). Nevertheless, phase II studies are likely to be used to determine the dose response characteristics (i.e. how does efficacy and tolerability vary with different doses). This means you could potentially be treated with a relatively high or low dosage of the new investigational drug. In summary, the trial is designed to determine if the new treatment works well enough to test in a larger phase III trial.
  3. Phase III – The objective of a phase III trial is to conclusively establish if the investigational drug at specific dosage levels is efficacious and safe compared to standard therapy or placebo (though in cancer trials placebo would refer to current standard treatment for ethical reasons). Placebo is a drug that looks just like the investigational drug (sometimes referred to as a dummy drug). Neither your physician nor the patient will know whether they get the new drug or a placebo. Drug treatments are randomly assigned to participants as they enroll in the clinical trial (this is referred to as a double blind randomised trial).  Phase III trials are substantially larger than phase I and phase II trials. Phase III trials can in some instances include as many as 10.000 patients. These placebo controlled clinical trials are seen as the gold standard. These studies (and a successful outcome) are in most cases a requirement by the regulatory authorities and essential to the granting of a licence or approval to market the new drug.
  4. Phase IV – Once a product has gained an approval after the conduct of successful phase III trials, the pharmaceutical company will embark on phase IV trials. These are often very similar to phase IIIb studies and generally assess the safety, efficacy as well as the cost effectiveness of the new drug in a more real-life milieu.These type of trials are often criticised for lack of or minimal scientific validity. They are also often seen as a covert endeavour by pharmaceutical companies to market their new product. Nevertheless, as phase IV trials generally include a large number of patients with variations in severity or stage of disease, more can be learned about longer term side effects and safety, as well as rare side effects. In addition, investigators may learn about its use in other ways or how it interacts in combination with other treatments.

In summary, gaining access to new investigational drugs can be accomplished in several ways:

  1. Search and enroll in a clinical trial (find a clinical trial in EU or clinical trial in USA and rest of world)
  2. Register with MyTomorrows who may be able to facilitate access to compassionate use programmes of new investigational drugs
Please note: Any medical or scientific information published on this website is not intended as a substitute for informed medical advice from a physician and you should not take any action before consulting with a health care professional. For more information, please read my terms & conditions.

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