Commonalities in orphan diseases

Caroline Mathie

THE PLANNING SHOP international

In this article, Caroline Mathie explains how identifying commonalities in very different orphan diseases can help improve efficiencies in the drug development and commercialisation process in this field of medicine.

Orphan diseases are, by definition, rare and very different – having different treating clinicians and often different geographic distributions of prevalence.

Common features of the management of orphan diseases include the motivational characteristics of the clinicians as well as the approach to treatment. Such commonalities offer novel opportunities for both the pharmaceutical and market research industries.

Common clinician motivations

There are several patterns in the drivers that have led clinicians to become experts in their chosen fields:

• Interest in the science behind the disease,

• Pride and enjoyment in being seen as an expert,

• Satisfaction and enjoyment from doing something different.

An important component of understanding management practices is to appreciate the commonalities that have drawn clinicians into treating an orphan disease and to developing specialist expertise in it.

As such, if you are entering into a new orphan disease area, it is best to check variances in clinician motivation from what has been learnt about similar clinicians in other orphan diseases, rather than reinventing the wheel.

Commonalities of small numbers

Orphan diseases can be chronic, progressive, debilitating, disabling and / or life-threatening. Information is often scarce and research is usually insufficient. Patients face challenges in diagnosis / misdiagnosis, psychological burden and lack of support services. The common goals remain for patients to obtain the highest attainable standard of health and to be provided the resources required to overcome the obstacles frequently encountered in their lives, regardless of their specific condition.

There are many learnings regarding the logistics of recruitment for clinical trials and market research with extremely low prevalence diseases, that are common across markets. Sharing approaches, e.g. experiences with snowball recruiting, can be valuable.

Commonalities of multiple organ involvement

Many orphan diseases affect multiple organs and the referral and diagnosis patterns can be complex, and numerous specialties may be involved before a correct diagnosis is made.


“…if you are entering into a new orphan disease area, it is best to check variances in clinician motivation from what has been learnt about similar clinicians in other orphan diseases…”


After diagnosis, a multi-disciplinary approach is often required, presenting challenges as to whom to talk and about what aspect of the disease. The growing number of Centres of Excellence (CEs) provide this multi-disciplinary approach and they act as focal points for medical training, research and information dissemination, and may even embrace tele-medicine to ensure distant access to healthcare.

As yet, very few countries in Europe have experience of designating CEs for orphan diseases. With or without CEs, the stakeholder networks tend to resemble a wheel with spokes. In understanding orphan disease markets, it is therefore critical to identify the stakeholder(s) in the hub and their relationship and means of communication with those at the end of the spokes, who are likely to be specialists in their own field: e.g. surgeons.

Genetic familial link

As 80% of orphan diseases are genetic in origin, we know that there will be geographical variation in prevalence and that the familial component is critical. Examples include:

• Tay-Sachs disease – more common in Ashkenazi Jews, the Cajun population of southern Louisiana and some French Canadians particularly in East Quebec,

• Niemann-Pick disease – higher rates of Type A seen in the Ashkenazi Jews, Type C is most common among Puerto Ricans of Spanish descent, Type D has only been found in the French Canadian population of Yarmouth County, Nova Scotia,

• Certain types of muscular dystrophy – higher incidence in northern Italy.

This presents significant challenges, particularly in patient research – ‘friend-get-a-friend’ or family member techniques become invaluable in market research recruitment. In addition, social networking is an effective research tool and often support the adage ‘no-one knows more about a rare disease than the patient or those who care for them’.


“Many orphan diseases affect multiple organs and the referral and diagnosis patterns can be complex, and numerous specialties may be involved before a correct diagnosis is made.”


Paediatric link

Although 50% of orphan diseases affect children, the specialist treatment required may mean that the paediatrician is only one cog in the management machine. As generalists, paediatricians often do not have the training or experience to trigger thoughts of an orphan disease diagnosis.

Further challenges exist in that the majority of products used in the paediatric population are unlicensed for use in children, and the paediatrician may have little or no experience of the treatments required. Of the 148 orphan drugs approved in Europe between 2000 and 2009, only 38 were for paediatric diseases. Physicians therefore often administer drugs to children by decreasing adult quantities based on the lesser weight of the child, which can be extremely hazardous. To counteract this, the EU Regulation on Paediatric Drugs now includes:

• Obligation to paediatric research (PIP – Paediatric Investigation Plan) for every new drug developed for adults and having a potential use for children,

• 2-year extension of market exclusivity for orphan drugs,

• Implementation of a process to avoid unnecessary clinical studies on children,

• Specific label products studied in children and authorised: the Paediatric Use Marketing Authorization (PUMA).

Opportunities exist across most paediatric orphan diseases to improve diagnosis rates, perhaps through the education activities of Centres of Excellence. Schemes to achieve this in one indication could potentially be successfully transferred to another.


“…paediatricians often do not have the training or experience to trigger thoughts of an orphan disease diagnosis.”


Challenges for pharmaceutical companies

Many challenges exist for the industry in designing clinical trials, with relevant outcome measures, for the small and geographically dispersed patient populations. The low prevalence limits opportunities to perform multiple studies, whilst the heterogeneity of presentation and disease progression poses challenges to uniform treatment paradigms and study design.

There could be great benefit, and little competitive disadvantage, in industry sharing solutions to logistical issues in order to speed up trials.

Potentially many roles for independents

Significant inter-orphan disease commonalities exist. There are many opportunities for refining the efficiency in various aspects of the development and commercialisation process, if we search for commonalities rather than differences.



About the author:

Watch Caroline being interviewed on the newfound relevance of orphan diseases for the pharmaceutical industry:


Orphan Diseases Research Group at TPSi from THE PLANNING SHOP international on Vimeo.


Caroline Mathie is the Head of the Orphan Disease Specialist Research Group at THE PLANNING SHOP international (TPSi) – a market research-based brand consultancy.

After studying Medical Bio-chemistry, Caroline spent 14 years at IMS Health, over 10 years as an independent Director-level Consultant and 4 years as a Director at J &amp, D Associates.

Throughout her career, Caroline has had an active interest in orphan diseases. This has led her to develop expertise in a wide range of orphan disease conditions, including various lysosomal storage disorders.

In 2010, Caroline joined TPSi as Lead Research Director and Head of Orphan Diseases Specialist Research Group.

You can contact Caroline on +44 (0)20 8231 6888 or at

Is it time we focused more on commonalities across rare diseases?