Recommendation 4

Recommendation 4. Respond to the inherent uncertainty of rare disease, by facilitating connections with rare disease and patient advocacy groups, research including clinical trials, and new therapies and technologies as fewer than 5% of rare diseases have a curative treatment but knowledge is rapidly expanding.


Why this is important:

Rare disease and patient advocacy groups, also called patient support organisations or consumer health organisations, play a critical role in supporting people living with rare disease. These organisations:

  • Connect people living with a particular rare disease or umbrella group of rare diseases with one another for practical and emotional support
  • Are a credible source of information about a rare disease or group of diseases
  • Can drive research and advocate for better access to care, support, and treatments.

In this rapidly changing landscape, it is difficult for health professionals to keep up with the available information on management, therapeutics, research, and clinical trial opportunities. Patient advocacy groups are often important sources of expertise about conditions or groups of conditions. They can provide health professionals and people living with rare disease with deep, person-centred knowledge that can improve care and outcomes.19 These groups will often know of local and international research opportunities, including the availability of disease-specific clinical quality registries (Recommendation 3.2).

Connections between health professionals and patient advocacy groups are also mutually beneficial. Health professionals can contribute scientific and medical advice that strengthens the rigour, reliability, and credibility of patient advocacy groups. This in turn means they are better able to support people living with rare disease and other health professionals. It also increases the visibility of rare diseases and the growth of clinical networks with relevant experience.


How to progress Recommendation 4.1:

Identify patient advocacy groups that are relevant to your patients. Rare Voices Australia is the national peak body for Australians living with rare disease and advocates for policy as well as health, disability, and other systems for people with a rare disease. It hosts the national RARE Helpline (Appendix 2.2).18

There are several directories of patient support and advocacy groups, such as Rare Voices Australia’s A-Z Support Directory (Appendix 2.3).20 People living with rare disease have asked for introduction and connections to these groups as early as possible after a diagnosis. These groups can be very helpful for the person with the rare disease diagnosis as well as their family and support people.

If no group exists in Australia for a particular rare disease, international groups may be able to provide support; these may be identified through international portals such as Orphanet or GARD (Appendix 2.2). In some cases, people living with rare disease may be interested in setting up a patient advocacy group for their condition. If so, Engaged, Ethical and Effective: A Guide for Rare Disease Organisation Leaders in Australia (Rare Voices Australia) is a good starting point.21

Engaging with these groups can take many forms, including:

  • Referring people living with rare disease to them
  • Utilising information from their websites
  • Joining a scientific or medial advisory board
  • Reviewing the accuracy of patient-facing information.


Why this is important:

Limited knowledge and data are common features of rare diseases, making research critical to the current and future care of people living with rare disease. Reflecting this, Research and Data comprise one of three key Pillars in the Action Plan (Appendix 2.1).9

Rare disease research can include:

  • Clinical trials, including for advanced therapy medicinal products (advanced therapies), which are medicines for human use that are based on genes, tissues, or cells (see also Recommendation 4.3)
  • Undiagnosed disease programs (see Recommendation 2.3; Appendix 2.12)
  • Non-therapeutic studies (such as into quality of life or service utilisation).

For many people, clinical trials are the only way to access treatment. Research increases understanding of a condition, informs new treatments, and benchmarks outcomes and service provision.


How to progress Recommendation 4.2:

Health professionals have a key role to play as gatekeepers to research and clinical trials for people living with rare disease. Best practice in rare disease care can only be achieved by embedding data collection and connection to research and clinical trials into routine practice.

The first step is identifying opportunities for clinical trials, including through Centres of Expertise, patient advocacy groups and databases like Australian Clinical Trials86 and ClinicalTrials.gov (international) (Appendix 2.16).87 Health professionals can then link the family with the clinical trial team. Often, rare disease registries (see Recommendation 3.2) are set up with a key aim of linking rare disease cohorts to specific research and clinical trial opportunities, and thus are another reason to discuss and facilitate access to such registries for people living with rare disease.

Health professionals also have an important role to play in facilitating shared decision making around research, clinical trial participation, and clinical quality registries. Discussions may include uncertainty of treatment outcomes, risks and benefits in comparison to available treatments or no action, and explaining inclusion and exclusion criteria. Resources to inform such discussions are provided in Appendix 2.16 and 2.17.

A challenging aspect of connecting people living with rare disease to opportunities is simultaneously educating them about the importance of research and managing expectations. Health professionals should be prepared to discuss people’s disappointment and frustration when a clinical trial is not the right fit or is unavailable in Australia, or a treatment is not effective.

It is important to ensure sufficient time and access to expert information so that people do not feel rushed into making quick decisions, especially as access to some clinical trials may exclude them from future trials or therapies. Undiagnosed rare disease programs are typically led by researchers and academics. Health professionals have an important role in referring patients to these programs, usually via clinical genetics services (see Recommendation 2.3). Timely referral to undiagnosed rare disease programs is vital for those living with an undiagnosed condition, given they currently represent at least 50% of all people living with rare disease.88


Recommendation 4.3

Facilitate access to advanced therapies.

Why this is important:

Advanced therapies, also known as advanced therapy medicinal products, are innovative therapies based on genes, tissues, or cells.89 These therapies aim to prevent, change the course of, or potentially cure some diseases90 and are often aimed at rare diseases. There are only a few advanced therapies available at the time of writing. However, this field of medicine is undergoing rapid growth and many more are likely to be available soon. Without assistance from their health care team, people living with rare disease may not be aware of, or able to, access these products.

Examples of advanced therapies include:

  • Genetic technologies such as the CRISPR-Cas9 gene editing technology. Genetic manipulation technology has been used successfully in clinical trials, and the first CRISPR-based therapy, which upregulates useful compensatory fetal haemoglobin and reduces red cell sickling in sickle cell disease, has now been approved by regulatory authorities in the United Kingdom, United States, and European Union.91-94 Gene therapy is another mechanism for editing genes, and uses vectors to introduce working versions of genes. It has been used successfully in inherited disorders such as spinal muscular atrophy and eye diseases causing blindness.95,96
  • Biological therapies such as Chimeric Antigen Receptor (CAR) T-cell therapy. CAR-T is a form of personalised immunotherapy in which T cells from an individual are re-engineered in a laboratory to produce chimeric antigen receptor proteins on their surface.97 When reintroduced into the patient, these receptor proteins bind to antigens on cancerous cells allowing targeted cell killing. This has been used for leukaemia, lymphoma, and multiple myeloma.

How to progress Recommendation 4.3:

As advanced therapies are usually delivered in Centres of Expertise (see Recommendation 3), referring people with rare disease to these centres is critical. In many circumstances, these therapies will only be accessible through clinical research and trials.

Health professionals have a role in educating and supporting people living with rare disease by proactively exploring the evidence for, and availability of, advanced therapies. This should continue before, during, and after receiving new therapies (Appendix 2.17).

A potential challenge is that people living with rare disease who feel they have few options may seek unregulated and unproven cell-based therapies. These may be ineffective and/or pose the risk of serious side effects.98

If a health professional is concerned that a person is considering unregulated advanced therapies and/or is travelling abroad for treatment, they could:99

  • Discuss the risks and benefits of the therapy in a non-judgemental way
  • Discuss how to report side effects of the therapy, if they experience any
  • Advise they check regulations in the country they are considering travelling to
  • Link them to the Therapeutic Goods Administration advice on buying medicines and medical devices online100
  • Link them to the Smartraveller advice on going overseas for a medical procedure101
  • Provide resources about these options (Appendix 2.17 and 2.18).

As lack of access or delays in accessing effective treatments such as advanced therapies can contribute to poor mental health and wellbeing, people living with rare disease and their families/carers should be monitored and psychosocial supports provided if needed (see Recommendation 5).


Indicators of good practice

• Linking people living with rare disease and their families/carers with rare disease and patient advocacy groups
• Connecting people living with rare disease to research opportunities, rare disease registries, and clinical trials
• Supporting people who are participating in clinical trials and accessing novel therapies
• People living with rare disease and their families/carers are encouraged to connect with support groups, expertise, and research opportunities related to their rare disease
• Interactions with rare disease and patient advocacy groups and sharing of relevant information with people living with rare disease
• Capture of rare disease information and codes in electronic medical record data collection systems
• Engagement with emerging and advanced therapeutics
• Use of clinical trials databases
• Enrolment in clinical registries and natural history studies
• Referrals to Centres of Expertise
For useful tools and supports to help implement Recommendation 4, see Appendix 2.1, 2.16-2.18.