Setting up a clinical trial

New treatments for cancer come from work in the laboratory and also through the experiences of people affected by cancer. They may, for example, suggest areas of research that they feel are important.   

When a group of researchers has an idea for a trial they need to develop a trial plan, which is called a 'trial protocol'. This includes information on:

  • the reasons for doing the trial
  • the numbers of participants needed in the study
  • who can join the trial (eligibility criteria)
  • the treatment to be given
  • the medical tests needed
  • how, when and what information will be collected
  • how and when results will be released or provided to participant.

Every trial has a person in charge, usually a doctor, who is called the principal investigator. The plan is checked by other people with appropriate experience. This is called a 'scientific review panel' or 'peer review'. Often the plan is checked by cancer consumer groups (such as Cancer Voices).   

After the plan is confirmed, the research team needs to source money to run the trial. When they have funding they send the plan to an ethics committee which reviews the study for any potential ethical problems. The ethics committee may request changes to the plan to ensure participants in the trial are treated ethically and to ensure their privacy is protected. If the ethics committee is not satisfied with the plan it may refuse to approve the study in which case it cannot go ahead. Full details on ethics committees in Australia are available at: www.nhmrc.gov.au/publications/synopses/e72syn.htm

Cancer trials in Australia are funded by drug or device companies, government and cancer charities. It is expensive to run clinical trials. The research costs include: 

  • treatments
  • research staff to run the trial and collect the data
  • staff and computer technology to analyse the results
  • administrative costs - paperwork, overseeing the plan, data collection, results
  • costs of extra tests or hospital stays for participants.

Drug companies conduct trials looking at drugs they have developed. They usually supply the drug free of charge in these circumstances.

The federal government helps fund research through the National Health and Medical Research Council (NHMRC). 

Cancer research in Australia is funded by:     

  • the National Health and Medical Research Council       
  • other government and non-government organisations      
  • companies and individuals       
  • a large number of charitable organisations including the Cancer Councils from each state, the National Breast Cancer Foundation and the Prostate Cancer Foundation of Australia.

Some trials that recruit participants in Australia are international trials. This means they are run by organisations outside Australia. This includes the American National Cancer Institute (NCI) or the European Organization for Research and Treatment for Cancer (EORTC). 

Independent scientific review

This is when the plan for the clinical trial is checked and then approved by experts not involved with the trial development or conduct.

Consumer review

Some cancer research funding organisations have introduced a similar process so that consumer and community values can be factored into their funding decisions, for example Cancer Australia.

Ethics committee

An ethics committee consists of a minimum of eight people. It should have equal numbers of men and women and at least one third of the members should be from outside the institution for which the ethics committee is reviewing research. The committee has a chairperson and a group including at least two lay (community) people, a nursing or allied health professional, a person with a pastoral care role, a lawyer and at least two people with current research experience. Its members are appointed using an open and transparent process. For more information see the National Statement on Ethical Conduct in Human Research at:www.nhmrc.gov.au/publications/synopses/e72syn.htm.

The ethics committee reviews the trial proposal and decides whether the trial is ethical and if it can proceed. The ethics committee checks the trial plan as well as the patient information sheet and consent form. The committee makes sure that the information contains everything that a participant would need to know about the trial and that it is easy to understand. The ethics committee may ask the research team to make changes to the trial plan.   

Multicentre ethics committees can approve research at a number of sites. Research Governance Units carry out the site-specific assessments for multicentre research. They make sure that there are enough local resources to support the research.   

If the researchers or company sponsoring a trial make changes to the trial plan, they must notify the ethics committee. Serious unexpected side effects must be reported. The ethics committee may stop a trial by withdrawing ethics approval for it to be conducted at that site.

Large multi-centre trials use a Data and Safety Monitoring Board (DSMB) that monitors the trial. While the trial is in progress it will meet approximately once or twice per year. The researchers provide the DSMB with a report stating the number of participants recruited, the number of people who have withdrawn from the trial, side effects and early results. The committee will then make recommendations about whether the trial should continue, continue with some changes or be stopped. A Data and Safety Monitoring Board (DSMB) usually does not have the authority to stop a trial. DSMBs usually only recommend early stopping and the decision to do so or not rests with the Trial Management Committee. The DSMB will also inform the ethics committee of any important results. For a local trial, there is a person/s or committee with the expertise to advise the ethics committee about any serious adverse events in the trial.

 

When there is enough evidence from clinical trials that a new treatment is better than the existing standard treatment, there are still a number of steps before people can have access to the new treatment. These steps are to make sure that only the safest and most effective treatments are made available.

Therapeutic Goods Administration

If a number of trials find a new treatment to be effective and safe, an application is made to the Therapeutic Goods Administration (TGA) to have the treatment licensed for use in Australia. Not every new treatment needs TGA approval, only drugs and medical devices. The TGA carries out a range of assessment and monitoring activities to ensure therapeutic goods available in Australia are of an acceptable standard. It aims to ensure that the Australian community has access, within a reasonable time, to therapeutic advances. Unless exempt, therapeutic goods (either drugs or devices) must be entered as either 'registered' goods or 'listed' goods before they may be supplied in, or exported from Australia. For more information on the TGA go to: http://www.tga.gov.au/

The TGA has a committee that assesses in detail the information submitted. If the committee feels that the drug or medical device is effective and is safe, it is likely it will be approved. A drug that is approved by the TGA can be prescribed by your doctor. The problem is that it may be very expensive. In some circumstances the drug may be paid for by the hospital where you are being treated or it may need to be paid for by the patient.

Australian Drug Evaluation Committee

The Australian Drug Evaluation Committee (ADEC) was formed in 1963 and given the role of providing independent, scientific advice on new drugs to the federal government. The ADEC is appointed by the Minister for Health and Ageing and provides advice to the Minister and the Secretary of the Commonwealth Department of Health and Ageing through the Therapeutic Goods Administration. It reviews:

  • the quality, risk-benefit, effectiveness and access within a reasonable time of any drug referred to it for evaluation
  • medical and scientific evaluations of applications for registration of prescription drugs (e.g. new chemical entities, new forms of previously registered drugs and therapeutic variations to registered drugs).

The Committee also provides services to other government departments, committees and community-based organisations on a wide variety of regulatory matters related to prescription medicines. For more information see: www.tga.gov.au/docs/html/adec/adec.htm

Pharmaceutical Benefits Advisory Committee and Scheme

In most circumstances drugs approved by the TGA are then assessed by the Pharmaceutical Benefits Advisory Committee (PBAC), which makes recommendations about drugs which may be listed on the Australian Government's Pharmaceutical Benefits Scheme (PBS). By being listed on the PBS, drugs are made available at a subsidised rate to people who need them. The PBS provides reliable, timely and affordable access to a wide range of medicines for all Australians. For more information on the PBAC and PBS go to:http://www.pbs.gov.au/

The main priority for the PBAC is to consider the effectiveness and cost of a proposed benefit compared to alternative therapies. If it is felt the drug is cost effective, then the cost of the drug will be subsidised by the federal government. This means that there is a minimal cost to patients relative to the true cost to the drug. Not all drugs approved by the TGA are approved by the PBS. The assessment process by the TGA and PBS can take time. In some circumstances a particular drug may be available overseas before it is subsidised in Australia.

The three main sources of the principles (both ethical and practical) and regulations that guide the researchers who run trials are: