The UK hasn’t yet had a plan or a strategy for rare diseases, unlike countries such as France, which is now on its second national plan for rare diseases. So it was with trepidation that we awaited the announcement of the UK consultation, on Rare Disease Day.

No specific funding for rare diseases
The first disappointment was that I couldn’t find anywhere a commitment to specific funding for rare diseases. While the second French national plan allocates €180 million towards rare diseases, there’s no mention in the UK consultation document of any UK budget for rare diseases.

Business as usual
The second disappointment was that the consultation document reads like ‘business as usual’, with few new initiatives proposed.

Read the executive summary. It’s mainly a summary of existing measures or statements. Here are a few quotes from the document:

- ‘There are already national screening programmes for several rare diseases.’

- ‘The UK participates in the Orphanet website, which is quality assured and one of the most comprehensive websites on rare disease in the world. The NHS also provides information on a variety of websites such as NHS Inform, NHS Evidence and NHS Choices.’

- ‘In the United Kingdom there is a wide range of patient organisations which offer help and support to people with rare disease.’

What about recommending a host of new initiatives to build on this? For instance, Rare Disease UK proposed a long list of possible initiatives in its ‘Vision for the UK Rare Disease Strategy‘.

Not much on research
The third disappointment was the research section, which is one of the shortest sections of the document, yet the area most in need of investment in the UK.

It starts by saying that ‘the UK is at the cutting edge of research into rare diseases’. This may be the case, but it’s definitely not because of any concerted government funding.

That’s why the following sentence is so grating: ‘Research is carried out by universities, the NHS, and other organisations. It is funded by Government.’

As anyone in the UK working in rare disease research knows, there is no funding available from the government specifically for rare diseases. Having spoken to several government funding agencies, I can tell you that rare diseases are at the bottom of their priority list. They made it clear to me that rare diseases cannot compete successfully for funding against common diseases such as cancer or heart disease.

That’s been confirmed by our experience at the AKU Society and by other patient and academic groups. Our funding for research has come from private sources.

This is completely different for the clinical side, where the UK is well set up for the care of ultra rare conditions through its National Specialised Services, which has a pot of money specifically ring-fenced for these. Why can’t the UK government do the same for rare disease research?

There’s also little proposed in the consultation document for patient registries, despite the fact that it’s increasingly clear that a centralised registry for rare diseases would make a significant difference. Nor is there much about the need to carry out major public awareness campaigns to help the public understand rare diseases in more depth. The document mentions research that shows that ‘almost all United Kingdom respondents (93 percent) agreed that people are unaware of the real problems faced by those suffering from a rare disease’ – yet it does not present any strategy for remedying this.

A robust UK plan for rare diseases would include at the very least the following three action points:

1. A long-term budgetary commitment to rare diseases, particularly a ring-fenced pot of money for rare disease research. This would kick-start research in the UK and prove that the government really does support this sector.
2. A centralised registry for rare diseases. This would make a big difference for natural history and long term observational studies.
3. A major, government-backed public campaign for rare diseases on the same scale as the awareness campaigns for cancer or heart disease. The UK public has very little understanding of the scale of the rare disease problem and how it affects patients. This needs to change.

So have a read through the consultation document and do feed back your comments on the consultation response form. The more of us provide feed back, the better.

You can download the consultation on the UK national plan for rare diseases here.

My thinking has changed radically on this. On this 5th anniversary of Rare Disease Day, I am overwhelmed at how far we all have come and how much this simple gesture has done to draw the global rare disease community together.

Just think, for a moment, about the following, bearing in mind that the global theme for this year is “Solidarity”:

• While we all have different challenges and concerns, at this one time of the year, patients, government officials, medical professionals and the pharma/bio industry are all speaking together with one voice and one set of goals.

• In countries as diverse in other respects as Iran, the USA, China, and Pakistan, Rare Disease Day Partners are sharing the same theme, logo, poster, video, and key messages.

• In this era when the social media rule, it’s astonishing to see the volume of Rare Disease Day photos, stories, videos and blogs … some quite professional in nature and others obviously “home grown” … and the consistency in the messaging, regardless of the country of origin.

• The first year, Rare Disease Day was observed primarily in the EU and Canada. Last year, it was observed in 66 nations and this year the number will be even higher.

In the USA, where my organization sponsors Rare Disease Day, nearly 700 patient organizations, government agencies, medical societies, and companies have signed on as Rare Disease Day Partners, displaying the logo and supporting the goals of the day.

The videos this year have been particularly moving to me. Yann’s video message does a wonderful job of stating the themes and purposes of Rare Disease Day. Others, especially the ones featuring children and young people, tug at our heartstrings and leave us with an even greater sense of urgency to accomplish our goals. My personal favorites … and there are many … include a young girl named Gracie singing “Brave”, a song she has written about living with Schwachman-Diamond syndrome, and a six-year-old boy named Ian who concludes his video with the ringing declaration: “I’m a histio warrier!”

But the most wonderful thing about Rare Disease Day isn’t just that it draws people together and encourages solidarity. Rare Disease Day actually helps drive progress toward our stated goals: more research; more safe, effective treatments; greater access to treatments; and a greater emphasis on rare diseases globally as a public health issue.

In Europe, Rare Disease Day is a time to focus on the need for national plans and to remind everyone that the clock is ticking toward the deadline for accomplishing that. In the USA, the National Institutes of Health and several highly regarded medical research institutions are hosting scientific conferences focusing on rare diseases. The Food and Drug Administration will host its first-ever Rare Disease Patient Advocacy Day.

FDA had worried initially that it might “throw a party and no one would come.” To the contrary, the organizers actually had to close down the registration a week ago because they were at full capacity. Patients are thrilled. This is the first time most have ever ventured onto the FDA campus. And, from the Commissioner on down, senior officials will be on hand to answer questions, explain the terminology and the process, and talk about how patients can participate.

Similar things are happening around the world. So, I have long ago put away my initial skepticism. We all owe Yann and EURORDIS a debt of gratitude for creating Rare Disease Day. It has accomplished more in these five short years than anyone could possibly have anticipated when it all first began.

As we celebrate the International Rare Disease Day 2012 we are turning rare diseases into an international movement as well as into an international public health priority.  These are critical, unavoidable long term objective to sustain and boost national and regional dynamics as much as to enable global approaches when they are more relevant and efficient than national ones due to rarity.

One of EURORDIS aims – as stated in its Strategy 2010-2015 – and a main long term objective of the EURORDIS partnership with NORD are to support people living with rare diseases in becoming this international civil society movement speaking with one voice and gaining visibility as much as influence in international institutions.

The International Rare Disease Day, initiated in 2008 and organised by EURORDIS together with all national alliances and all stakeholders friends around the world, is a dynamic vector in achieving this objective. Rare Disease Day is a rapidly growing success reaching out to more countries – over 60 countries in 2012- and spreading the word thanks to local events, social media and viral communication. It is an essential campaign to raise public awareness, to attract attention of policy makers and a concrete common action to bear the sense of sharing common destiny and goals.

The International Conference on Rare Diseases & Orphan Drugs, of which I am one of the co-funding members, organized since 2005, first in Stockholm (2005), Madrid (2006), Brussels (2007), Washington (2008) and Rome (2009) are now moving to Buenos Aires (2010), Tokyo (2012) and soon Shanghai (2013) bringing together leaders from the patient advocacy organizations, public policy, academia and industry is a useful action to leverage the local efforts in gathering the relevant stakeholders and bringing the challenges of rare diseases to the surface. ICORD has also the potential to create a core international community of rare disease leaders sharing the same vision and common objectives.

The International Consortium for Rare Disease Research, initiated in 2010 by the European Union with the United States, Canada, Japan and other active countries and private players, is an essential initiative. The IRDiRC is now fully established since 2012 to promote globally coordinated policy for the development of the knowledge base for rare diseases as much as new diagnostic tools for most rare diseases and the ambitious objective of 200 new additional therapies for rare diseases by 2020.  Following our advocacy, EURORDIS and other main national rare disease organisations are full members of IRDiRC Executive Committee.

The immediate use of OrphaCode, and tomorrow a possible WHO classification of rare diseases in the next ICD 11, is instrumental to shape international health information systems on rare diseases and enable new international collaboration. This OrphaCode is already widely and increasingly used around the world. These efforts are significantly supported by the European Union.

EURORDIS has initiated a Joint Declaration “Rare Diseases: an International Public Health Priority” currently reviewed and to be adopted in the coming year by umbrella rare disease patient organisations from around the world so to speak with one common patient voice to international institutions such as WHO and OECD, and take our future advocacy efforts at a new level.

EURORDIS will facilitate improved communication between these umbrella organisations in order to share information, exchange experience and coordinate limited international actions. Being itself an organisation covering 48 countries and working in seven languages, EURORDIS is better equipped to support these efforts and create the “Rare Disease International” network. This was discussed in January 2012 in Tokyo between EURORDIS for Europe, NORD for USA, CORD in Canada, NZORD in New Zealand, TZORD for Taiwan, Geizer for Argentina and the Japan Patients Association.

In parallel, EURORDIS and NORD will continue and grow their joint efforts to create International on line communities of patients and families, involving patient organizations from around the world when they exist, so to raise their disease awareness internationally, to ease exchange and mutual support across countries and continents, and to promote new patient generated knowledge.

This vision and step wise approach was presented by EURORDIS last month at the International Conference on Rare Diseases and Orphan Drugs (ICORD) in Tokyo, Japan, and welcomed by participants.

By dedicating a limited 1% or 2% of our respective resources to this international cooperation, we can make a huge difference to the hundred millions of patients living with a rare disease around the world while enhancing the effectiveness of our efforts in our respective remits.

In introducing this bill, Sen. Hagan said her goal was to empower the Food and Drug Administration (FDA) to ensure a clear and effective pathway that will encourage innovative products to benefit patients and improve public health.

In her statement introducing the legislative proposal, Sen. Hagan mentions a study that NORD conducted earlier this year cataloguing FDA flexibility in the review of 135 non-oncologic orphan drugs approved since 1983. That study showed that in two-thirds of the cases, flexibility was employed in the review process, either based on specific policies adopted over the years or on a case-by-case basis.

After releasing this study at its annual conference in October, NORD commended FDA for demonstrating flexibility in the review of products for small patient populations. But NORD went on to encourage FDA to establish written documentation to ensure that the flexibility is applied in ways that are consistent and transparent.

Specific features of the TREAT Act that NORD feels are important are:

• It enhances and codifies the accelerated approval process.
• It addresses concerns of the rare disease community related to conflict of interest provisions regarding participating on advisory committees.
• It provides greater clarity, consistency, and transparency in the review process.
• And it encourages innovation and the adoption of modern scientific tools in regulatory science.

At the NORD/DIA Conference in October, National Institutes of Health Director Francis Collins, MD, said the science of rare diseases is advancing faster than at any other time in history. The global body of knowledge and understanding related to rare diseases is expanding at a very impressive rate.

NORD believes the TREAT Act has the potential to provide FDA with the authorities and tools needed to promote a similar level of innovation and advances in regulatory science and the review process. It would promote the use of modern scientific tools and methodologies, while maintaining the necessary controls related to safety and efficacy.

And if the goal of bringing innovative, safe, effective new therapies to market is achieved, the ultimate winners will be patients, their families, and patient organizations.

The First Lady of Georgia Mrs Sandra Elisabeth Roelofs opened the conference in a very engaging manner: “All together we can make a difference for the ones who suffer from rare diseases” “The diseases are called rare because each disease affects few patients but all together rare disease patients represent a lot of people” “Rare diseases are not just about health and medical issues, they are also about the education and social issues and human rights issues looking around the corner at people living with rare diseases” “”Georgia is a modern reforming country. A country of opportunities. You expect the impossible in Georgia. The Health care system is being reformed as in many countries and as elsewhere it is never easy as healthcare is always an issue in most countries. Georgia is a country with problems. 50% of our population is poor. And every person deserves the right to have access to quality care even poor people with rare diseases. We still have a job to do”.

Mrs Roelofs is the First Lady of Georgia since 2004 when her husband Mikheil Saakashvili assumed the presidency. Mrs Roelofs is 43 yrs old and has two sons. She is Dutch and speaks French, English, German, Russian, and Georgian.  She graduated from the Institute of Foreign Languages in Brussels and the International Institute of Human Rights in Strasbourg. She met Mikheil Saakashvili in 1993 while attending a course on human rights in Strasbourg and later that year moved to New York where she worked at Columbia University and a Dutch law firm. In 1996 the couple came to Georgia, where Mrs Roelofs worked for the International Committee of the Red Cross and the Consulate of the Kingdom of the Netherlands in Tbilisi. In 1998 Roelofs founded the charity foundation SOCO which has the primary focus of implementing the programs funded by Western European and Georgian companies and individuals and is aimed at supporting low income families. Since setting new targets in 2007, SOCO has been actively taking care of reproductive health and child welfare in Georgia. In 2007 Mrs. Roelofs founded Radio Muza, the first Georgian radio dedicated solely to classical music.

Mrs Roelofs further explain how she became involved in rare diseases ” My involvement in health started with palliative care, thereafter HIV/AIDS, reproductive health, children and maternal health” “I became a WHO Goodwill Ambassador specially focusing on the Millenium Development Goals in the area of child and maternal health” “In SOCO we have established an alliance for rare diseases. We have established an office providing information to patients on diseases, diagnosis and care as well as lobbying the government, industry and stakeholders to take action for rare diseases” “Few years ago there was not much going on rare diseases in Georgia except few isolated patient organisations and healthcare professionals” “I am happy to use my title and name to improve the situation of people living with rare diseases in Georgia”.

Mrs Roelofs concluded with thee words “With a combination of creativity and enthusiasm we can get unexpected results” “I will see many of you on 29th February in Brussels for the Gala Dinner organised by EURORDIS on Rare Disease Day, an important event to raise funds and to promote the cause of people living with rare diseases. I can help get other influential people to come and speak at the conference”. “For rare diseases we are not talking about Europe only but globally”.

The 1st US Conference on Rare Diseases and Orphan Products, co-organised by NORD (National Organization for Rare Disorders, USA) and the DIA (Drug Information Association), took place in Washington DC from 11 – 13 October 2011. Organised in partnership with the FDA, NIH and EURORDIS, this first conference was a huge success, assembling over 250 attendees who benefitted from discussions on drug development, de-risking investments, challenges in patients’ access, changes in the orphan landscape, the FDA and NIH processes, the US health care reform, changes in insurance reimbursement, off-label issues and compassionate allowance.

Separate tracks for patient advocates and organisations, researchers/drug and device companies, and investors were proposed. A stellar lineup of speakers, including NIH Director, Francis S. Collins, and Social Security Administration Commissioner, Michael J. Astrue, contributed to its impact and importance.

The second event in this new transatlantic series will be the 6th European Conference on Rare Diseases and Orphan Products (ECRD 2012 Brussels) taking place in Brussels, Belgium from 23 – 25 May 2012. Co-organised with the DIA Europe and NORD, this foremost conference on rare diseases will bring together all stakeholders in the European rare disease community at a crucial juncture.

The value of this trans-Atlantic series of conferences with patient-driven agenda partnering with regulators, policy makers, healthcare managers, industry, investors, academic leader is already tangible. Back from Washington, I see three strong points:

• The converging calls by NORD and EURORDIS for an official policy of flexibility by drug regulatory and health technology agencies for rare diseases and orphan drugs. Francis Collins, NIH, highlight the huge current scientific potential to develop innovative approaches to treat or cure rare diseases. This analysis is shared by Ruxandra Draglia-Akli, Director for Health Research at the European Commission, who initiated the International Rare Disease Research Consortium with the ambitious goal of 200 new therapies for rare diseases by 2020. But the pathway is narrow and obstacles many between development between orphan designation and approval, called the Death Valley. A key leverage to activate is the way regulations are implemented on both side of the Atlantic. Experience shows that the European Medicines Agency (EMA) has a well established track record of flexibility with half of the 70 orphan drugs being approved based on conventional study design and also half being approved at the end of Phase 2. EMA has even adopted few years ago an Official Guideline on Alternative Study Design on Small Populations. An analysis prepared by NORD and FDA and first presented at the Washngton’s Conference on 25 years of experience  shows that out of 135 non-cancer orphan therapies approved for new chemical entities, 45 were “conventional studies”, 32 “administrative flexibility”, 58 “case by case flexibility”. NORD wants that FDA adopt an official policy of flexibility for orphan drugs as FDA did in the past for HIV and Cancer. EURORDIS is considering calling for similar offcial policy of flexibility for orphan drugs by the EMA ( providing opinions) and European Commission (DG SanCo providing decisions). Such official policy of flexibility by the main regulatory authorities for orphan drugs in the world would be particularly relevant and consistant with the objectives 200 new therapies by 2020 of the International Consortium strongly supported by the EU European Commission, US NIH as well as Canada, Japan and others. Although, if these two policies were to be parallel it will not be sufficient : hence my strong call on behalf of EURORDIS at the US Conference for a much closer and real collaboration between FDA and EMA. This transatlantic collaboration works effectively at the stage of the orphan designation, it is exemplary and good but not enough. Collaboration needs now to exist for protocal assistance so to agree on best and most realistic international study design so to generate faster better data for the risk & benefit assessment. We need a rolling-on joint protocol assistance dedicated to orphan drugs, both knowledgeable about the reality of rare diseases and flexible in its regulatory

• The US Health Care Reform, the USA are confronted with the emergence of health technology assessment and its impact on orphan drugs. Considerations for the need to assess the effectiveness and comparative/relative effectiveness are growing ; In this regards, EU is much more advanced on this debate. The concepts are already clarified and approved as well as core methodology for the assessment. New approaches such as the scientifc assesssment of the Clinical Added Value of Orphan Drug, conditional pricing and reimbursement, and policy of pricing and reimbursement based on data generated are mature policies well on track for implementation. In the fielf of orphan drugs, these new policies are triggered by the dialogue between EURORDIS, industry, EU Member Sttaes autorities and European Commission. NORD has announced in the concluding panel of the Washington’ Conference that it will now look at these new approaches as policies transferable to the USA. Pivotal between the regulatory procedures and the health technology assessment : the marketing autorisation. Here too, new approaches are emerging, from industry and GSK in particular, calling for « Progressive Marketing Approval » one more bridge to link up between data generated for clinical trials and real life use. In all cases, post-marketing obligations or evidence generation plan to generate data on effectiveness, would gain from closer closer collaboration – here too – to generate post marketing evidence on risk, benefits and effectiveness fater with better quality data and increased statistical power. Both previous themes are connected to need to put in place international rare disease registries supporting pre-approval and post-approval research activities.

• The potential for actual coordination on rare disease registries. In EU several projects are complementing each other to shape policy scenario based on best practices and public health needs (such as the EpiRare project) and to build EU-wide infrastructure for databases, biobanks and registries (recent FP7 Call). This is linked to the Working Group on Registries and Biobanks of the International Consortium which will define common international policies such as minimum data set, standard operating procedures, interoperability, etc. The NIH is supporting similar analysis, exchange of best practices, library of resources on registries. We are not yet there, but almost there. With goodwill on all sides, real resource saving and life saving convergences are at our door step.

Related links:
Updates from the conference (courtesy of NORD): http://rarediseases.org/patients-and-families/patient-meetings/dia-nord-oct-2011
Images from the conference (courtesy of NORD): http://rarediseases.org/news-events/news/2011-summit

No European policy is possible without a simple, clear strategy, accepted by most interest parties, and with adequate governance. This is what the EU has provided for its most successful policies such as on energy and common markets. And this is what we have now for rare diseases.

We have a clear strategy and objectives spelled out in several policies and legislations. We have the support of the European Commission, the European Council and the European Parliament. We have governing bodies within the EC, with the EU Committee of Experts on Rare Diseases (EUCERD) and at the European Medicines Agency (EMA), with the Committee on Orphan Medicinal Products (COMP). We have international ambition with the International Consortium on Rare Disease Research.

We have structured our action around civil society – with EURORDIS- and around quality medical information – with ORPHANET. In the coming years we will have structured European Reference Networks of Rare Diseases gathering experts, centres and diagnostic labs, and we will have EU wide infrastructures for clinical trials, biological resources and registries.

Our common challenge is now to agree on common good practices and to monitor our achievements. To achieve these goals, we need continued political support – which we can contribute to stimulate through awareness and advocacy – and more resources, which means more budget for the 2014-2020 EU Programmes, in particular for research and public health.

Concrete and worthwhile actions speak to EU citizens. Actions in the field of rare diseases are an example of the need and the usefulness of more Europe today!

Rare diseases affect 3.5m people in the UK (see http://www.raredisease.org.uk/). If you include their family members (approximately four people per nuclear family), that means 14 million people have direct experience of a family member living with a rare disease. I’ll repeat that:

14 million people.

The total UK population is just under 60 million people. This means that 25% of the UK population has direct experience of a close family member living with a rare disease.

That’s one in four.

If you include grand parents, children, close cousins and close friends, the figure climbs higher, maybe even to half the UK population, or even more.

So why is there no mass movement? Where are the millions of mums, dads, brothers, sisters, sons and daughters, cousins, friends, colleagues, grand-mothers and grand-fathers of people with rare diseases? Why aren’t they on the streets, shouting about the injustices faced by their suffering family members and friends?

Maybe they’re too tired and exhausted from caring for them? Maybe they’re discouraged and don’t believe they can make a difference? Or maybe they think the disease is too rare, so why should anybody care?

I’ve often told people that my two boys have a rare disease (Alkaptonuria, or Black Bone Disease). Generally, people are sympathetic. I can see their sorry faces. ‘That’s a shame. I’m glad that’s not me,’ I can hear them think.

Others are more hostile. One family friend once said, ‘Who cares about your kids’ rare disease. There are more important things to worry about in the world.’

Unfortunately, I believe his reaction is common – it’s just that most people won’t say it out loud. The term ‘rare disease’ doesn’t work well as a way of raising awareness and generating support. When faced with the evil of cancer or the suddenness of heart disease, rare diseases seem more like a curiosity, something that isn’t widespread and that isn’t relevant to most people. There’s always an uphill struggle to explaining that rare diseases are common. But even then, most people don’t feel all that concerned.

So should we rebrand rare diseases? Should we find a term that challenges people? That makes them feel directly concerned? That makes them feel like they need to take action urgently?

This is a tough one. And I don’t pretend to have a solution. That’s why I’m writing this blog post – to generate some thinking. Last night, our brainstorm, which included a global branding expert, the head of a growing rare disease foundation, and the director of digital media in a major health foundation, looked at the options:

• Rare diseases: an accurate description, but makes people think that it doesn’t affect them. It reduces engagement.
• Orphan diseases: symbolic, but creates confusion in the public’s mind: could be diseases affecting orphans in Africa.
• Genetic diseases: could work, although few members of the public understand the term ‘genetics’. Sounds technical, scientific. Also, some genetic diseases are not rare diseases.
• Extreme diseases: captures the imagination and makes you wonder what it’s about. Many rare diseases do present themselves as extreme versions of common diseases (Alkaptonuria is an extreme form of osteoarthritis).  But this term can sound too sensationalist. And many common diseases are also extreme in their manifestations.
• Inherited diseases: easier to understand for the average member of the public. Everyone knows about inheritance. It engages them, makes them think ‘could I have an inherited disease?’. But some rare diseases aren’t inherited, and some common diseases have inheritance factors.

I’d love to hear what others think. In the end, maybe we should stick to the term rare diseases. Maybe we should accept that it’s not perfect, but that it’s the best we have at the moment. Or maybe there’s a better way out there? A way that will immediately grab the public’s attention, make them realise we need to take action, and kickstart a mass movement on a scale we’ve never seen before.

Email me on nick@akusociety.org if you’d like to discuss this further.

I went home last night and was lying in bed thinking about it, unable to sleep. The conversation had awakened in me a deep sense of injustice. How are we ever going to help the 8% of the population that has one of the 7,000 known rare diseases if most of the major funders still don’t see it as a priority?

It’s not the first time this has happened. Let me give you another example. A few months ago we applied to another major funder. Our application was so strong, our publications list so impressive, that we got selected out of 1,400 applications to go through two rounds of internal reviews, received glowing peer reviews, and got to the final assessment panel. Yet the questions of the panel showed that they had barely read the proposal and had no understanding of why studying rare diseases is so important.

I believe there are two key problems here:

1. Most funders – at least in the UK – are still stuck in the old numbers game. Cancer or heart disease, they say, are the biggest killers. Hence they invest in these areas.
2. The majority of funders have deeply flawed assessment processes. They don’t know how to select good applications. And I believe that’s a big reason why so much scientific research fails.

So what are the solutions? Here are my recommendations:

1. We need to build a mass movement for rare diseases. The other day I was walking through Cambridge and saw hundreds of women dressed in pink for Cancer Research UK’s Race for Life event. It’s the biggest women-only charity fundraising event in the UK, raising millions for Cancer Research UK and helping put cancer high on the public and political agenda.

We need a similar mass movement for rare diseases. It’s the only way of convincing the public, the politicians, the funders and the health system that the millions of people with rare diseases really count.

2. We need to show how studying rare diseases has wider implications. William Bateson, the famous Cambridge geneticist who died in 1926, once said ‘treasure your exceptions’. Bateson was a friend of Sir Archibald Garrod, who first identified Alkaptonuria as an inborn error of metabolism in 1901. Both Bateson and Garrod knew that the study of rare diseases – the ‘exceptions’ – was a golden gateway to understanding common diseases. More than 100 years later, our Alkaptonuria scientists in Liverpool are discovering that Alkaptonuria is an excellent model for understanding osteoarthritis – a very common disease – proving that Bateson was right.

3. We need to reform how traditional funders work. Traditional funding processes are often just form-filling exercises: if you tick the right boxes, lobby the right people and know how to fill in the form correctly, then you may get funded. Most traditional funders then provide grants for one to three years, forcing scientists to spend their time scrambling around for more funds rather than focusing on scientific research.

Traditional funders miss out the most important criterion in the success of any project: the strength and track record of the research team. And the only way to assess a team is by spending time with them – lots of time.

Fortunately, there is an answer to this. It’s called venture philanthropy. It’s based on how venture capitalists choose companies to invest in. They spend a lot of time on their due diligence: meeting the team, assessing their track record, discussing their strategy. And once they’ve found a team of A-players, they support it over a long period of time. Not a one or even a three year grant, but sometimes up to 10 years or more. Venture philanthropists know that persistence and commitment pays off.

That’s what we’ve done with the AKU Society. We’ve raised £1m in donations from private sources, and we’ve invested all of it in an amazing research team in Liverpool, going from the most basic to the most clinical science. Over the past eight years, we’ve developed a symbiotic relationship with them, where we all work together for the same objective: finding a cure to Alkaptonuria.

If you want to find out more about venture philanthropy, check out the European Venture Philanthropy Association: http://evpa.eu.com.

4. We need independent funders dedicated to rare diseases. There’s an urgent need for a major foundation dedicated exclusively to funding research into rare diseases and supporting rare disease patient groups. We need something as ambitious as Cancer Research UK, which raises £0.5bn each year from the public for cancer. We need a Rare Disease Foundation that will support any rare disease – not just a small subset or those of its founders – over long time periods, using a venture philanthropy model, and with a focus on finding cures. It needs to be independent and free from political or corporate influence. It needs to exist for patients and only for them.

5. We need to support existing international initiatives on rare diseases and use these to lobby our national governments. Thanks to the work of groups such as Eurordis and NORD, the European Commission and the National Institutes of Health are leaders in supporting rare disease research. For instance, the EC’s FP7 health call that was announced this week has strong support for rare diseases. The International Rare Disease Research Consortium launched recently is another excellent initiative. However, compared to the scale of the need – the 7,000 rare diseases, most of which have no cure – it’s still a drop in the ocean. That’s why we need to build on these initiatives to get our national governments and funders to take action.

So that’s my five point plan. If you’re interested in discussing this further, do get in touch. My email is nick@akusociety.org or visit the AKU Guide for Rare Disease Patient Groups: http://akurarediseaseguide.wordpress.com.

This is an important topic for everyone in the rare disease community.  NORD President and CEO Peter L. Saltonstall submitted the following  comments as a Letter to the Editor of JAMA:

To The Editor, Journal of the American Medical Association:

The article “Characteristics of Clinical Trials to Support Approval of Orphan vs Nonorphan Drugs for Cancer” by Kesselheim et al  (JAMA. 2011;305(22):2320-2326. doi: 10.1001/jama.2011.769) presents the predictable finding that pivotal trials for orphan cancer drugs often have fewer patients and use different trial designs than trials for drugs for more prevalent cancers.  Rare diseases by definition have small patient populations; trials in such populations will commonly have fewer patients than those for more prevalent diseases.  Recruitment of participants for such studies is challenging, and trials of new agents for orphan diseases may, of necessity, be non-randomized and open label.

The article asserts that “safety and efficacy questions have emerged about some of these agents” and offers examples of one orphan drug being removed from the market for safety reasons in the U.S., and two orphan drugs not being reimbursed in the U.K., largely due to high cost. However, we are not aware of a higher rate of safety and efficacy questions for orphan products than for drugs for more common diseases, and the article offers no support for questioning the safety or effectiveness record of orphan drugs.

The rare disease patient community is thankful that the Food and Drug Administration (FDA) and other regulatory agencies recognize the special challenges posed in testing orphan drugs.  FDA has shown flexibility in accepting protocols for pivotal trials of orphan drugs, while maintaining its traditionally high standard that all drugs must be proven safe and effective for their intended populations.  Furthermore, the law places responsibility on manufacturers to report signals of risk associated with all approved drugs; manufacturers of orphan drugs are required to abide by that requirement just like manufacturers of other drugs.

There are still more than 6,000 rare diseases with no approved medications at all.  These diseases affect as many as 30 million Americans.  Most of these diseases are chronic, life-threatening or lifespan-reducing.  More than half of the patients are infants or children. There is a continuing and critical imperative for innovation to find treatments for patients with rare diseases, while assuring that these treatments are effective  and safe for the target populations.

We who advocate for patients with rare diseases believe that more resources are needed to support innovative research. The medical and regulatory communities understand the special challenges inherent in developing treatments for rare diseases. They must also recognize the need for flexibility in clinical trial design and the fact that patients with such disorders are willing to accept reasonable risk in return for hope of effective treatment.

Sincerely,

Peter L. Saltonstall

President and CEO, National Organization for Rare Disorders (NORD)