The ALS/MND associations wish to co-operate with clinicians, researchers and commercial sponsors to accelerate the pace and broaden the scope of clinical trials that may benefit patients now and in the future. In many countries the associations are in active contact with large numbers of patients and can offer a unique communication channel for information, education and recruitment.
The associations recognise the importance of operating within national and international codes of ethics, and according to the principles of good clinical practice and scientific method. All parties to every ALS/MND trial are asked to note this statement of good practice, which reflects the concerns of patients and care givers and is drawn from observation and experience in the first major trials.
1. The Disease
- ALS/MND is at present irreversible and invariably fatal;
- the interval from definite diagnosis of the disease to death ranges from a few months to many years, with a general life expectancy of 2-3 years;
- uncertainty is a consequence of the disease that overlays the physical effects;
- aspects of the organisation of clinical trials are shaped specifically by the natural history of the disease;
- the disease undermines human dignity and independence; clinical trials must not compound this, and all parties to trials must take steps to maintain these human rights.
2. Clinical Trials
- until clear recommendations for therapy are established, trials of any potentially therapeutic agent or technique are to be encouraged;
- it is recognised that at present these are medical experiments, not treatments;
- a goal of every trial should be to establish with the maximum certainty, the degree of efficacy or otherwise of the trial compound or technique;
- observational studies are welcomed as long as data are also recorded rigorously, and the limitations of any conclusions made are acknowledged.
3. The Volunteers
- the Helsinki Declaration of Human Rights makes it clear that the expected benefit of medical experiments must outweigh any expected harm;
- this remains true of an illness which is invariably fatal and trials should routinely include quality of life assessment;
- a condition of any voluntary participation in trials must be informed consent. This imposes an obligation on trial organisers to provide adequate and intelligible information to patients and their carers;
- participation in trials and treatment of volunteers must avoid all discrimination on the basis of gender, age, disability, ethnic origin, political or religious belief, sexual orientation or nationality, except that exclusion on the basis of age or disability may form part of the trial protocol where such exclusion will improve the accuracy of trial outcomes;
- participation in trials invariably imposes a burden on the diminishing resources of ALS/MND patients and caregivers, which must be acknowledged;
- after the conclusion of the formal trial, the trial compound should be made available to all volunteer participants whilst data analysis and/or licensing procedures are pursued.
4. The Investigators
- biomedical science in general is poorly understood by the lay public, and explanation of the rationale for controlled trials in particular requires time and effort;
- planning is required, before any trial begins, for the potential outcomes and possible ethical and practical dilemmas that may result;
- investigators will help to reduce uncertainty by strict adherence to trial protocols, and by securing their clinical peers’ compliance to the highest standards.
- proper counselling and/or psychological support should be provided as appropriate to the trial protocol.
- local ethical approval is essential at every centre with compliance with the Helsinki Declaration and the Nuremberg Code;
- controls, inclusion/exclusion criteria, methods of drug administration and other aspects of methodology should be carefully considered to add as little as possible to the physical and psychological burden of the disease;
- psychological measures should be included in trial protocols both to monitor the impact of trials upon volunteers, and to evaluate this as a potentially significant variable.
- data and conclusions must be disseminated and published as rapidly as possible after the end of a trial, consistent with scientific integrity and accuracy;
- where drugs are administered outside the trial protocol, it should be demonstrable that this will not affect the trial itself.
6. The Associations
- should at all times protect individual confidentiality.
- should provide impartial and considered information which acknowledges the interests of patients and caregivers;
- can assist in the recruitment of volunteers by proper education and information provision subject to the Data Protection Law existing in the country administering the trial;
- can help to educate the ALS/MND community on the constraints of scientific method, on the need for experiment and for properly designed, blinded placebo controlled trials.
- advise and/or warn the investigators and manufacturers of matters adversely affecting patients and their carers;
- should assist in devising fair and equitable access to trials and/or trial compounds.
7. The Pharmaceutical Industry
- should recognise the unique problems relating to this disease;
- should recognise the need for provision of the fullest information at all stages of planning and execution of trials and licensing, consistent with commercial confidentiality;
- should require investigators to take a proper educational role;
- must exert pressure to ensure that trial protocols are observed until findings are complete and that such adherence should be part of the documented trial protocol;
- should provide for the cost of continued administration of trial compounds to volunteers until analysis and/or licensing is complete;
- should help to ensure that whatever the results of the trial , all results are communicated, due caution is observed in media reporting, and that unrealistic expectations are not raised;
- should provide for the cost of volunteers, travelling expenses;
- should take account of the cost of information and education in budgeting for trials.
International Alliance of ALS/MND Associations
Revised November 1995; November 1997; November 2004