Rare Diseases and Orphan Products Accelerating Research and Development (2010) / Chapter Skim
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2 Profile of Rare Diseases
2 Profile of Rare Diseases
Pages 41-72
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From page 41... ...
Once accurately diagnosed, patients with rare conditions may be treated by physicians who have little evidence or guidance to help them -- physicians who may experience the frustration imagined by the patient quoted above. Particularly when a condition is extremely rare, patients and families frequently have to travel long distances to consult with the few experts who have experience in treating and studying their rare diseases; patients and their families may even relocate to make access easier.
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From page 42... ...
For other conditions, including a number of the relatively more common conditions such as cystic fibrosis, sickle cell disease, and some cancers, publicly and privately sponsored research has generated a knowledge base that may encompass epidemiology (including natural history studies) , genetics, disease mechanisms, diagnostic tests and standards, biomarkers and outcome measures, effective treatments, and evidence-based guidelines for clinical services.
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From page 43... ...
1 Under the Orphan Drug Act as described in Chapters 1 and 3, once a drug is designated as an orphan and undergoes further development, it then can be approved and qualify for 7 years of marketing protection even if the prevalence of the disease or condition at the time of approval exceeds the rare disease threshold.
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From page 44... ...
Policy makers may also consider epidemiologic information on prevalence and disease burden -- in combination with scientific, political, economic, ethical, and other factors -- in making decisions about the allocation of resources for biomedical research. Decisions about research spending, for example, sometimes favor the relatively more common rare conditions such as ovarian cancer, neurofibromatosis, and sickle cell disease, but decision makers also have directed resources to extremely rare diseases, consistent with the value judgments underlying the adoption of special policies to encourage research on rare diseases.
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From page 45... ...
Although natural history studies are not the primary focus of government- or industry-funded research, NIH and pharmaceutical companies as well as other entities do sponsor natural history studies of varying scope and complexity.3 For example, members of the NIH Rare Diseases Clinical Research Network (see Chapter 5 and Appendix E) are undertaking such studies for a number of rare conditions, including several neurological disorders and several forms of vasculitis.
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From page 46... ...
, programs on infectious diseases and birth defects track and report data on several rare conditions. The Agency for Toxic Substances and Disease Registry (ATSDR)
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From page 47... ...
As described in Chapter 1, the European Union defines a rare disease as one with a prevalence of no more than 50 people per 100,000 population, whereas the United States sets a numerical maximum of fewer than 200,000 people in this country. Prevalence is a function of both the incidence of disease (number of new cases reported in a given period)
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From page 48... ...
Figures 2-1A-D show the distribution of rare conditions according to prevalence as presented in the Orphanet report. They reveal an overall distribution that is highly skewed to very rare conditions.
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From page 49... ...
PROFILE OF RARE DISEASES 500 450 Number of diseases 400 300 200 71 100 30 21 13 0 0.1-10.0 10.1-20.0 20.1-30.0 30.1-40.0 40.1-50.0 Prevalence per 100,000 FIGURE 2-1A Number of rare diseases by prevalence up to 50/100,000. Figure 2-1A 250 198 Number of diseases 200 150 100 59 38 33 33 50 23 22 18 15 11 0 <0.1 1.1- 2.1- 3.1- 4.1- 5.1- 6.1- 7.1- 8.1- 9.1 -1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 Prevalence per 100,000 FIGURE 2-1B Number of rare diseases by prevalence of 10/100,000 or less.
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From page 50... ...
Therefore, these estimates are an indication of the assumed prevalence but may not be accurate. Figure 2-1D The factors cited illustrate problems inherent in trying to develop reliable prevalence estimates for rare conditions -- individually and collectively.
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From page 51... ...
In the past two decades, epidemiologic, molecular, and other research that takes advantage of scientific and technological advances in the biological sciences has greatly increased the number of rare diseases that have an identified cause -- usually, although not invariably, genetic. The Orphan Drug Act, the Rare Diseases Act, and other policy initiatives discussed in this report have contributed to this knowledge by focusing attention, resources, and incentives on the study of rare conditions and products to treat them.
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From page 52... ...
. To cite other examples, the Vasculitis Research Consortium, which is part of the NIHfunded Rare Diseases Clinical Research Network, is investigating six forms of vasculitis (a group of rare conditions affecting blood vessels)
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From page 53... ...
Fortunately, the scientific and technical advances cited in Chapter 4 are making gene identification easier, faster, and less expensive. Infectious Agents A number of rare diseases have infectious causes.
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From page 54... ...
tryptophan, a dietary supplement.10 It is likely that far more types of poisoning could be listed as rare conditions than are included in the list maintained by the Office of Rare Diseases Research (ORDR)
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From page 55... ...
. Certain rare conditions are caused by the persistent adverse or toxic effects of treatment for another disease.
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From page 56... ...
For example, thalidomide, a drug best known from the late 1950s for causing birth defects in children of mothers who were prescribed the drug for morning sickness, is now FDA-approved for treatment of two rare conditions (multiple myeloma and erythema nodosum leprosum)
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From page 57... ...
recommended screening for 29 mostly inherited, serious, rare conditions (Watson et al., 2006)
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From page 58... ...
Parents may first learn of their membership in a rare disease population after a child's screening. In addition to allowing treatment at the outset to help prevent damage, the early identification of children with rare disorders can facilitate research by (1)
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From page 59... ...
One dilemma for clinicians and patients is that many rare diseases have neurological, digestive, or other symptoms that accompany a number of common and rare conditions, and depending on the disease and the individual patient, laboratory results may or may not be definitive. Physicians normally will consider common conditions that are consistent with the available
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From page 60... ...
Family members may be advised about their options to be tested. Many organizations that educate, assist, and advocate for patients with rare conditions seek to educate physicians about the disease.
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From page 61... ...
includes brief overviews of treatment for several hundred rare conditions, but the committee is not aware of reviews of treatment practices and options over the spectrum of rare diseases.16 Various textbooks, online sites, and other resources advise on treatment for a broad range of infections, including some that are rare; other resources advise on treatments for a broad range of poisonings, again including some rare poisonings. Many rare diseases have been discovered relatively recently, so researchers have had limited time to work on identifying their causes and mechanisms of disease as the basis for investigating treatment targets or preventive strategies.
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From page 62... ...
Table 2-2 illustrates the range of treatments -- from surgery to diet and from stem cell therapy to environmental adaptation -- that may be deployed for specific rare conditions. Some of these therapies have been used for decades, while others have emerged through technological advances.
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From page 63... ...
Curative Treatments Truly curative treatments for rare conditions are themselves rare. Immediate treatment may be completely successful for all or most cases of certain rare infections (e.g., Tropheryma whipplei)
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From page 64... ...
Organ transplantation is considered curative for a few rare conditions, for example, heart transplantation for hypoplastic left heart syndrome. For carefully selected subsets of patients, bone marrow transplantation or transplantation of stem cells from umbilical cord blood is, if successfully performed, considered a cure for Diamond-Blackfan anemia, WiskottAldrich syndrome, and paroxysmal nocturnal hemoglobinuria as well as as some cancers (Filopovich et al., 2007; Brodsky, 2009; Clinton and Gazda, 2009)
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From page 65... ...
Symptomatic and Functional Therapies Symptomatic treatments are vital to patient well-being for many chronic rare conditions, especially when more definitive therapies are not available. Painful and distressing symptoms of many rare as well as common diseases include pain, nausea, bladder or bowel dysfunction, itching, dizziness, movement limitations, and speech dysfunction to name a few.
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From page 66... ...
One common mission of advocacy organizations is to educate clinicians about rare conditions as a means of improving the provision of care, including the appropriate consideration of new diagnostic and therapeutic options. Depending on the condition and the organization, other strategies may include the development of clinical practice guidelines, quality improvement and assessment programs (including incentives for meeting quality standards)
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From page 67... ...
Pediatric-Adult Care Transition Children form a substantial part of the population with rare conditions. Although many rare diseases are fatal in infancy or childhood, early diagnosis and improved treatment for a number of conditions have increased the number of infants and children who survive to adulthood.
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From page 68... ...
To the extent that young people in transition lose health insurance through a parent's work-based coverage or under Medicaid, the shift from pediatric to adult care may create additional complications and risks. Medicaid covers a range of special services for children that are not usually covered for adults and that may be particularly important for children with severely debilitating rare conditions.
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From page 69... ...
High and burdensome costs are not unique to rare diseases, but a number of factors can push patient, family, and societal costs higher for rare conditions than for more common ones. The search for an accurate diagnosis can be not only time-consuming but also expensive.
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From page 70... ...
They have joined together to form support and advocacy organizations -- some focused on individual conditions, others encompassing a number of related conditions, and yet others such as NORD and the Genetic Alliance acting as umbrella organizations and advocates. Although not focused solely on rare conditions, the Genetic Alliance convenes a range of activities to help rare disease and other groups develop, function effectively, and collaborate.
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From page 71... ...
Walks, runs, bike races, telethons, celebrity appearances, and other events involve people in highly visible activities that draw attention to rare conditions and the toll they take. In addition, NORD and other groups promote awareness of rare diseases generally, including through activities associated with Rare Diseases Day.
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From page 72... ...
Sometimes separately but also in concert, rare disease organizations and their umbrella organizations have worked together on a broad agenda that includes funding for research and technological innovations that will identify the mechanisms of rare diseases and translate these findings into studies that ultimately lead to better ways to prevent, diagnose, and treat these diseases. As this report illustrates, the confluence of scientific advances and policy initiatives provides new opportunities to accelerate this progress.
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