The sad events at
Northwick Park Hospital involving six healthy men being taken seriously ill during the trial of a new monoclonal antibody drug,
TGN1412, being developed to treat chronic inflammatory conditions and leukaemia, raises the complicated issue of the entitlement of those made ill through their participation in clinical trials to compensation.
Purpose of clinical trials
Clinical trials are a series of health studies, involving either ill patients or healthy volunteers, which compare a new or different type of treatment with the best treatment currently available. For example, in cancer care, trials have been used to try out new types of radiotherapy, chemotherapy and surgery. All new forms of treatment must go through these clinical trials before they are licensed for use in the UK.
Types of clinical trial
There are different stages of clinical trials.
Phase I trials (sometimes called early treatment trials) aim to test the safety of various doses of a new drug. This includes looking at the side effects of a drug – for example, does it make people sick, raise their blood pressure etc? Phase I trials involve only a small number of people, who may be healthy volunteers.
The testing of TGN1412 performed at Northwick Park Hospital was a Phase I trial involving 6 volunteers being given the test drug and two volunteers being given the placebo.
Phase II trials test the new drug in a larger group of people who are ill, to see whether it has any effects suggesting that it might help them. Usually a few hundred people are involved at this stage. Phase II trials also look in more detail at the safety issues covered in Phase I trials.
Treatments only move into a Phase III clinical trial if Phases I and II suggest that a drug might actually be useful in ways that patients would regard as important. Phase III trials test new drugs in larger groups of people who are ill. Phase III trials compare the new drugs with whatever treatments are currently in use, or occasionally with a placebo. These trials look at how well the new treatment works in practice, and at any side effects. They usually last longer than Phase II trials – typically a year or more. Often several thousand patients will be involved in a Phase III trial. They may use different hospitals in different countries. Large numbers of people are needed because researchers are often trying to detect moderate but important differences between treatments.
Finally, Phase IV trials involves further trials of drugs that are already licensed.
Procudure for obtaining authoristaion to run a clinical trial
Different types of organisations (including drug companies, the National Health Service, Universities or even medical charities) commission drug trials. They can either carry out the trials themselves or, more usually, instruct others (including NHS Hospitals, private Hospitals or even specialist drug trial companies) to actually carry out these tests. The research team carrying out the trial should consist of doctors, nurses and other relevant professionals.
In the Northwick Park case, the test drug
TGN1412 was made by the German drug company
TeGenero and the trial was being run by the American specialist drug testing company
Parexel.
Those commissioning and running a trial must draw up a detailed written protocol setting out the basis for the trial including information on what question the trial is seeking to address, how many people will be involved, who can take part in the trial (the eligibility criteria), what treatments will be compared, what tests people taking part in the trial will have and when they must have them and details about how and when information will be collected.
The protocol is then sent to an independent Ethics Committee for approval. The are 190 Ethics Committees in the UK. Ethics Committee members include researchers and health care professionals as well as members of the public. The Ethics Committee is usually part of the same Hospital or Trust where the trial is being carried out although the Ethics Committee should be completely separate from those proposing to carry out the research. The trial cannot start without the Ethics Committee’s approval.
Any trial also needs to be approved by the
Medicines and Healthcare Products Regulatory Agency (MHRA). The Agency forms part of the Department of Health. Its job is to protect and promote public health and patient safety by ensuring that medicines, healthcare products and medical equipment meet appropriate standards of safety, quality, performance and effectiveness, and are used in the right way.
Taking part in a drug trial
Clearly there may be a number of possible benefits of taking part in a clinical trial, including receiving a new treatment before it is widely available and helping produce information of use to the patient and others in relation to the safety and effectiveness of a possible new treatment.
However, there are also a number of possible risks of taking part in a clinical trial including experiencing unwanted side-effects as well as being given a new treatment that may be less effective than the standard treatment.
Before making the decision whether or not to take part in a trial, the person must be given the opportunity to discuss the trial with those running it and then be provided with detailed written information in relation to the trial. This information should include details of the type of treatment to be given, the possible benefits and the possible side effects.
If the person decides to take part in the trial, he or she will be required to a sign a consent form confirming their agreement to take part in the trial.
The law relating to clinical trials
The European Union Clinical Trials Directive (2001/20/EC) was transposed into national law through the
Medicines for Human Use (Clinical Trials) Regulations 2004.
These Regulations place legally defined responsibilities on those commissioning and carrying out drugs trials as well as clear responsibilities on the Ethics Committees and the MHRA. These include the need for those commissioning and carrying out drug trials to have adequate insurance should the trial go wrong.
Entitlement to compensation for health problems suffered as a result of participation in a trial
Those who have suffered ill health as a result of their participation in a drug trial may be entitled to compensation. However, generally it will be necessary to show that the health problems are serious and beyond those discussed with the person or identified in writing, before the person agreed to participate in the drug trial. Therefore, if for example, the person is warned that he or she may suffer headaches or nausea while taking part in the trial, then it is unlikely that they would be able to claim compensation if they went on to suffer these side effects. Furthermore, no compensation is likely to be payable to the person simply because the trial drug does not have the intended benefit.
However, a person may be entitled to compensation if he or she suffers more serious injury, not identified by the researchers orally or in writing at the onset of the trial.
As with injuries suffered in other contexts, the amount of compensation is likely to depend on the pain and suffering caused and the losses, such as loss of earnings or greater care requirements, that flowed from the injury.
Possible legal claim
The injured person may have a legal claim against those commissioning or carrying out the drug trial on the basis that that they have been negligent in relation to the research or development of the drug under trial or that the trial drug was defective.
It is difficult to generalise about the prospects of a legal claim succeeding without investigating the specific facts of the drug trial and circumstances surrounding how the injury was sustained.
For example, what injuries were suffered and is it accepted that the injuries were caused by the trial drug? Were the injuries identified as a possible side effect in the written information provided to the person before the start of the trial? Was this injury totally unexpected or was there information from previous animal or human trials of the drug suggesting that this may be a problem? Was all of the relevant information disclosed to the Ethics Committee, MHRA or person participating in the trial? Was the trial protocol followed by those performing the tests?
ABPI Guidelines
In reality, obtaining compensation for health problems caused by participation in drug trials is usually made easier through claiming against those commissioning or running the drug trials through Clinical Trial Compensation Guidelines issued by the
Association of British Pharmaceutical Industry.
In fact, there are different ABPI Guidelines depending on the phase of the trial, although the compensation provisions in both are similar.
Compensation for injuries suffered in Phase I trials
Phase I trials are covered by “Guidelines for Medical Experiments in non-Patient Human Volunteers” of March 1988 (as amended in May 1990).
These Guidelines identify the need for a model agreement between those commissioning or running the trial and the person participating in the study and provide a suggested model agreement.
The Guidelines state
“The agreement should clearly record the obligation the pharmaceutical company or research establishment has accepted in terms of financial rewards for participation and compensation in the event of injury. In particular, the volunteer should be given a clear commitment that in the event of bodily injury he will receive appropriate compensation without having to prove either that such injury arose through negligence or that the product was defective in the sense that it did not fulfil a reasonable expectation of safety. The agreement should not seek to remove that right of the volunteer, as an alternative, to pursue a claim on the basis of either negligence or strict liability if he is so minded.” (para 11.7)
“ Where pharmaceutical companies sponsor studies to be performed in outside research establishments, the responsibility for paying compensation should be clarified and reflected in the contractual documentation with the volunteer. Where the sponsor company is to provide the undertaking regarding compensation, it is recommended that the sponsor company enters into an unqualified obligation to pay compensation to the volunteer on proof of causation, having previously protected its rights to recourse against the research establishment in its agreement with that establishment, to cover the position where the negligence of its contractor may have caused or contributed to the injury by the volunteer. A volunteer can reasonably expect that compensation will be paid quickly and that any dispute regarding who will finally bear the cost of the compensation paid to him will be resolved separately by the other parties to the research.“ (para 11.8)
“ It is recommended that a simple arbitration clause is included as part of the provisions concerning compensation for injury, whereby any difference or dispute in relation to the implementation of the compensation provisions may be resolved with a minimum of formality.“ (para 11.9).
Compensation for injuries suffered in Phase II and III trials
Phase II and III trials are covered by the ABPI “Clinical Trial Compensation Guidelines” of January 2001. These state that
“compensation should be paid when, on the balance of probabilities, the injury was attributable to the administration of a medicinal product under trial or any clinical intervention or procedure provided for by the protocol that would not have occurred but for the inclusion of the patient in the trial.” (para 1.2)
It continues that
“the amount of compensation paid should be appropriate to the nature, severity and persistence of the injury and should in general terms be consistent with the quantum of damages commonly awarded for similar injuries by an English Court where legal liability is admitted.” (para 4.1)
Furthermore, the Guidelines also state that
“In any case where the company concedes that a payment should be made to a patient but there exists a difference of opinion between the company and the patient as to the appropriate level of compensation, it is recommended that the company agrees to seek at its own cost (and make available to the patient) the opinion of a mutually acceptable independent expert, and that opinion should be given substantial weight by the company in reaching its decision on the appropriate payment to be made.” (para 4.3).
While it is generally preferable, if possible, to pursue a claim for compensation through the Guidelines, it is important to be aware that there are a number of important exclusions to claiming under the Guidelines. Compensation is not generally payable under the Guidelines if the injury is simply for
“temporary pain or discomfort or less serious or curable complaints” (para 1.4) although the Guidelines do not state what is meant by less serious or curable.
Furthermore, compensation is not payable if there was a significant departure from the agreed protocol, the failure of the treating doctor to identify or deal with an adverse reaction or the contributory negligence of the person taking part in the trial (para 3.4).
It is therefore important to establish as soon as possible whether the person commissioning or running the drug trial is a member of the Association of the British Pharmaceutical Industry and / or has confirmed that the guidelines will be adhered to in the event of injury caused to a patient attributable to participation in the trial in question. This information should be included in the written documentation provided to the person before the beginning of the drug trial. It should also be information provided to the Ethics Committee as part of the information submitted when seeking authorisation of the drug trial.
Sean Humber a Partner in the Human Rights Department of the firm has successfully obtained compensation for several individuals through the ABPI Compensation Guidelines in the last three years.
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