Although randomised controlled trials (RCTs) are the cornerstone of evidence-based medicine, studies that evaluate multiple crossovers between intervention and comparator in a single patient, or ‘n-of-1 trials’, can help to inform personalised treatment decisions. N-of-1 trials rigorously measure intervention effects for individuals and can generate valuable data in situations where RCTs are not feasible or appropriate, such as in rare diseases or when treatment effects are heterogeneous. Well conducted n-of-1 trials can also provide a source of population data for meta-analyses, important for conditions where there is little RCT evidence.

In 2013, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement was released, providing evidence-based recommendations for the minimum content required in a published clinical trial protocol. An extension to these guidelines has recently been published in The BMJ by Dr Antony J Porcino and colleagues. The SPIRIT extension for n-of-1 trials (SPENT) provides guidance on the development and publishing of n-of-1 trial protocols to improve completeness and transparency.

The SPENT guidelines present the minimum content needed for complete and transparent reporting of n-of-1 trial protocols.

SPENT contains 14 extension items specific to n-of-1 trials, a checklist for n-of-1 trial protocol abstracts, and additional guidance for eight SPIRIT items providing information tailored to the n-of-1 trial context. To ensure concordance between the reporting of trial protocols and results, SPENT was developed in line with the CONSORT extension for n-of-1 trials (CENT) reporting guidelines.

The authors highlight that many aspects of n-of-1 trials are the same as parallel-group RCTs and, as such, many aspects of SPIRIT apply to SPENT. Stakeholders and reviewers are strongly encouraged to adopt SPENT to increase the standardisation, completeness and comparability of n-of-1 trial protocols. The authors conclude that increased uptake of SPENT will improve the quality of these protocols, their subsequent review and use, and ultimately, the resulting trial.

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Summary by Alice Wareham PhD, CMPP from Aspire Scientific

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With thanks to our sponsors, Aspire Scientific Ltd and NetworkPharma Ltd

Saturday 29 February was the thirteenth international Rare Disease Day organised by EURORDIS. This year, the overarching message was powerful: Rare is many, rare is strong and rare is proud!

Rare is many. Rare is over 300 million people around the globe.

Rare is strong. The rare disease community joins together across borders and diseases to raise awareness and advocate for equity.

Rare is proud. Show your support for the rare disease community with pride!

Over 300 million people worldwide are living with a rare disease; however, misdiagnosis can be common, leading to treatment delays. In addition, there are often inequalities and difficulties with access to treatment and care, which can create a heavy social and financial burden for patients with rare diseases. To improve treatment options and access for these patients, there is a need for additional research. A number of initiatives currently support research into rare diseases, including: the European Reference Networks, the International Rare Diseases Research Consortium and the EU Framework Programme for Research and Innovation Horizon 2020.

To raise awareness of rare diseases, events are organised in February each year by patient organisations, healthcare professionals, researchers, policymakers and other members of the rare disease community. This year, nearly 500 events were held in over 100 countries worldwide. In the UK, some of the events included:

• Rare Film Festival.
• Drug Repurposing for Rare Diseases Conference (Findacure).
• Rare Disease Day Westminster Reception.
• Show Your Rare hands-on activities (Great Ormond Street Hospital).
• Genetics Matters: lay lectures and hands-on research tables (Newcastle University).

Over the next decade, the goal of Rare Disease Day is to achieve equitable access to opportunities (including access to health and social care, diagnosis and treatment) for people living with a rare disease by:

1. advocating for the social inclusion of people living with a rare disease
2. including rare diseases in universal health coverage.

To help achieve this aim, why not get involved in Rare Disease Day 2021 by organising a local event. You could:

• hold a meeting, workshop or conference
• organise an art, photography or essay-writing competition
• coordinate a walk or march
• plan a fundraising event
• arrange a face painting event to #ShowYourRare.

Logo source: https://www.rarediseaseday.org/downloads (EURORDIS)

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Summary by Emma Evans PhD, CMPP from Aspire Scientific

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With thanks to our sponsors, Aspire Scientific Ltd and NetworkPharma Ltd

1. Establish data availability – accelerated regulatory approval can impact timeframes and early data availability may be required. Communication points must be carefully selected as new results can dramatically change the landscape.
2. Establish knowledge gaps – gap analyses can optimise the impact of results on current understanding.
3. Think outside the box – small patient numbers can mean that single-arm and case studies are more appropriate forms of publication.
4. Consider alternative data analyses – less common statistical methodologies may need to be used due to small data sets, which can be more difficult to convey effectively.
5. Establish consensus on disease management – treatment guidelines may not be available for rare diseases, so it is important to garner clinical opinion.
6. Consider integrated data disclosure planning – patient identification can be a concern due to small patient populations and combined data disclosure may aid anonymity.
7. Maximise patient access – open access, plain language, lay summaries and social media can all be explored as ways of effectively reaching the patient.

The European Medicines Agency estimate that approximately 30 million individuals in Europe live with a rare disease and that “medical and scientific knowledge about rare diseases is lacking”, highlighting the importance of ‘getting it right’ when it comes to publishing such work.

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Summary by Jo Chapman PhD from Aspire Scientific

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With thanks to our sponsors, Aspire Scientific Ltd and NetworkPharma Ltd