Clinical trials in rare disease

The number of clinical trials in rare diseases is growing drastically from the last ten years to more than 500 compared to a few hundred clinical trials. Currently, more than 400 orphan designated drugs are commercially available, and around 1000 drugs are undergoing clinical trials. But still, the clinical trials in rare diseases present many challenges compared with clinical trials in common diseases, such as availability of a few sites, identification of quality sites, patient retention, and many more.

Clinical trials in rare disease

Drug development in rare diseases is often challenging and the clinical development part of drug development is complex and critical compared to the non-rare disease drug development.

The prominent reasons Include disease-specific complexities and the small number of patients scattered around the globe. Consequently, clinical trial sites for rare diseases become more demanding in terms of patient recruitment, the requirement of experienced investigators, knowledgeable site staff, and adequate resources to execute the rare diseases clinical trials. 

Some interesting facts about rare diseases research

  • Blood, central nervous system, and respiratory are the leading orphan drug therapeutic areas, accounting for more than 50% of the non-oncology orphan drug market.
  • Paroxysmal nocturnal hemoglobinuria (PNH), Maroteaux-Lamy disease, Multiple myeloma, and Chronic lymphocytic Leukaemia, (CLL) are leading indications in the Orphan drug market.
  • Worldwide, non-Hodgkin lymphoma (NHL) was granted the most orphan drug designations followed by acute myeloid leukemia (AML) and pancreatic cancer.

Before moving into further details, let’s look at the worldwide statistics of rare diseases

Worldwide rare disease statistics

  • Approximately 10% of the global population is affected by a rare condition with an estimated 15.2 million individuals expected to have clinical genomic testing in the next 5 years facilitating research and innovation in diagnostics and therapeutics.
  • Only 5% of rare diseases have an approved treatment option.
  • 80% of these have genetic causes that mean people tend to be born with a rare disease and 30% of the affected children die before reaching their fifth birthday.

A total of 2,249 clinical trials are going on rare diseases globally with major studies in North America followed by Europe and East Asia. As you can see the majority of the rare disease clinical trials are going on in the United States and France.

Clinical trials in rare disease

As more rare diseases are identified and rare disease clinical trials expand to new indications, it is also important to find eligible clinical trial sites. Conducting a rare disease clinical trial is complex and getting it right from the beginning of identifying eligible sites is critical in particular for patients and their caretakers. A study says, 69% of sponsors find choosing a clinical trial site for rare diseases is one of the toughest challenges.

Click here for details about rare disease clinical trial sites in the USA

How clinical trials in rare disease are different from common diseases?

  • Rare disease sites are fewer in number and patient recruitment takes longer than non-rare disease sites.
  • Site selection is limited by treatment-naive patients or the general prevalence of the disease by region, requiring the sponsor to open sites in countries that normally would not be considered for clinical trials. 
  • Rare disease sites are preferred to be chosen where the patients are being treated regardless of their geography and sponsors do not have the luxury to choose sites.
  • Rare disease sites and clinical investigators require expertise with patient-centric interactions and providing services such as travel arrangements, telemedicine, technology support to improve the clinical trial experience for patients and their caregivers.
  • Specialized training is required for sites and investigators with limited clinical research experience.

Let’s have a look at common challenges for setting up the right sites for rare disease clinical trials.

Top challenges for clinical trials in rare disease

  1. Require multiple sites in different countries capable of recruiting and adhering to varying country-specific regulations. Clinical assessments and equipment may vary across countries and introduce variability.
  2. Locating research sites with experience in trials specific to rare indications
  3. Sites with better infrastructure and site staff suitable for rare disease clinical research
  4. The limited number of research sites complementary to patient locations.
  5. Continuous engagement of sites for retention of patients for a longer duration
  6. Sites without research experience can be more challenging to identify and qualify
  7. Sites with access to the target patient population may not necessarily have the most experienced site staff

Recognizing the tactical complexities for investigational sites participating in these trials and optimizing the patient experience is critical for patient participation and retention. Other challenges that are associated with rare disease trial sites are exceeded site activation timelines due to patient recruitment.

Thus, identifying appropriate rare disease sites is crucial for the success of the rare disease clinical trial. 

Strategies to overcome challenges for clinical trials in rare disease

To overcome the challenges in the rare disease clinical trials, it’s obvious to have a well-planned clinical development strategy. Some of the strategies include

  • Conducting feasibility studies to identify qualified sites and investigators for rare disease clinical trials to overcome patient recruitment barriers
  • Conducting feasibility assessment of the capability of the site/investigator to perform tasks or techniques associated with the treatment to reduce the risk of selecting sites that are not able to meet enrollment or adhere to the study protocol. 
  • Site collaboration to facilitate recruitment and retention
  • Patient-centricity is a key and should be considered when activating a trial site
  • Patient registries like NORD, EURORDIS, CORD, patient advocacy groups, or other support organizations accelerate patient recruitment and enable better site planning before initiating a trial for rare diseases.
  • Sponsors should embrace new technologies that build deeper engagement with patients and sites to adapt to the evolving regulatory demands for drugs for rare diseases.

Rare disease clinical trial sites in North America 

Rare disease & sites in the United States

Liver Cancer

Hepatocellular carcinoma is the most common malignant neoplasm of the liver arising from hepatocytes. It is more frequent in adults than in childhood and the majority of the cases are diagnosed at an advanced level of the disease. Symptoms such as abdominal pain, yellowing of the skin, unintended weight loss, or hepatic mass may develop later in the disease. It is most prevalent in the world but is rare in the United States affecting around 60,000 patients.

Currently, a total of 3104 clinical trials are registered on with 844 ongoing clinical trials in the United States. Clinical trials of liver cancers are conducted at centers like UC Davis Medical Center,  nationally recognized as a leader in cancer research. Patients in clinical trials are closely followed by experienced professionals and offer patients access to more than 150 cancer clinical trials at any given time giving the most appropriate standard treatment.

Pancreatic Cancer

Pancreatic cancer occurs due to the abnormal growth of cells of the pancreas and forms tumors that interfere with the way the pancreas work. It can be hard to treat as it is often found late and spreads quickly. In the United States, less than 200,000 people are diagnosed with pancreatic cancer. Some risk factors for developing pancreatic cancer include smoking, diabetes, chronic pancreatitis, and hereditary disorders.

In the United States, 1545 clinical trials were registered on pancreatic cancer. Clinical trials were performed at Holy Name Medical Center where high-quality clinical trials are conducted in multiple therapeutic areas and have a team with more than a decade of research experience of nearly 165 clinical trials.

Renal Cancer

Renal cell carcinoma is the most common form of cancer in which kidney cell growth is out of control and forms a tumor. Renal cell carcinoma accounts for approximately 30,000 new cases per year in the United States. It occurs more commonly in males than in females and the first symptom is passing blood in the urine. A total of 1966 clinical trials are registered worldwide with 1015 ongoing trials in the United States.

A clinical trial with Brendan Curti MD, as a principal investigator was conducted at Portland Providence Medical Center on Renal cancer. It’s a full-service medical center specializing in cancer and cardiac care. It offers an innovative multidisciplinary approach to clinical research including studies of new surgical techniques, targeted therapy, immunotherapy agents, etc.

Soft Tissue Sarcoma

Soft tissue sarcoma is a malignant tumor that starts in the tissues like bone or muscle. It often has no obvious symptoms and depends on where cancer develops. It is estimated that approximately 13-16,000 new cases are due to sarcomas in the US. Currently, 1258 clinical trials are registered on soft tissue sarcoma in the United States.

Stanford Medical Center located in California has been conducting clinical trials on Soft Tissue Sarcoma. It serves as a teaching hospital for the Stanford University School of Medicine and is ranked as one of the best hospitals in the United States. It has over 250 actively recruiting clinical trials and offers leading-edge research and compassionate care.

Fallopian Tube Cancer

Fallopian tube cancer is an abnormal growth of malignant cells in one or both fallopian tubes that carries an egg from the ovary to the uterus. It is mostly diagnosed in post-menopausal women and other causes be Inherited gene mutations. Usually, the cancer is not diagnosed until it is advanced and symptoms may include bloating, abdominal pain, vaginal watery discharge.

A total of 531 clinical trials are registered on with 450 ongoing studies in the United States. Clinical trials on Fallopian tube cancers were performed at centers like M D Anderson Cancer Center is a comprehensive cancer center in Texas. It has a suitable infrastructure and experienced clinical researchers who conduct hundreds of clinical trials of rare cancers.

Esophageal Cancer

Esophageal cancer is a rare form of cancer characterized by uncontrolled cellular growth that arises in the esophagus. It is asymptomatic in the early stages but individuals may have difficulty in swallowing as cancer grows. It affects males more often than females and around 17,000 people are diagnosed in the United States each year. Mayo Clinic in Rochester conducting clinical trials on esophageal cancer in the United States.

Rare disease & sites in Canada

Ovarian Cancer

Ovarian cancer refers to any cancerous growth that begins in the ovaries. It is more difficult to treat and can be fatal when it spreads within the pelvis and stomach. About 240,000 women are diagnosed each year with ovarian cancer in the world and it is estimated that 3,100 Canadian women will be newly diagnosed with ovarian cancer. 

A total of 227 clinical trials are registered on ovarian cancer in Canada. Rare disease clinical trial sites such as Princess Margaret Cancer Centre have been working on Ovarian Cancer in Ontario. This hospital is one of the five largest cancer centers in the world.

Multiple Myeloma

Multiple Myeloma is a rare form of cancer characterized by excessive proliferation of plasma cells, a type of white blood cell found in the bone marrow. The most common symptom associated with multiple myeloma is bone pain, especially in the lower back and ribs. It is more common in males than in females. It is believed that around 100,000 Americans have Multiple myeloma.

Clinical trials of Multiple myeloma are conducted at centers like London Health Sciences Centre is a hospital network in London and has disease-specific multidisciplinary teams of experienced professionals. One of their notable achievements is the regular recruitment of 250-400 patients each year to 50 to 70 active trials. 

Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) are a rare group of blood disorders that can occur when the blood-forming cells in the bone marrow become abnormal. An individual may suffer from frequent infections, weakness due to low blood cell counts. A total of 2031 studies are registered worldwide with 102 clinical trials going on in Canada.

Clinical trials on Myelodysplastic syndrome were performed at the Odette Cancer Center at Sunnybrook Research Institute (SRI). It provides care to patients with various types and stages of cancer. Various clinical trials are run out of the center with a focus on cancer prevention, detection, and patient education. 

Rare disease & sites in Mexico

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a form of cancer where the rapid growth of abnormal cells in the bone marrow interferes with normal hematopoietic cell production. More men than women are affected by AML and prevalence is slightly more in Europe. It can spread quickly in the blood and to other parts of your body becoming life-threatening without treatment.

In North America, 1965 clinical trials are registered on Acute myeloid Leukemia with 15 studies ongoing in Mexico. Cooperative Group of Malignant Hemopathies, in Huixquilucan conducting clinical trials on Acute Myeloid Leukemia.


Tuberculosis is a bacterial infection commonly caused by Mycobacterium tuberculosis and spread by airborne droplets or saliva. It mainly affects the lungs leading to breathing difficulties.  In the later stages of lung involvement, blood may appear in the sputum. A total of 1097 clinical trials are registered worldwide with 13 studies ongoing in Mexico. National Institute of Public Health located at Morelos conducting clinical trials on tuberculosis infection.

Rare disease & clinical trial sites in Europe

Rare disease & sites in France


Malaria is a communicable disease spread through the bite of the Anopheles mosquito caused by the plasmodium parasite. Chills and fever commonly occur but severity depends on which parasite species causes the infection. Symptoms may develop a week after exposure to the mosquito or may show up after months, even with preventive treatment. The overall rate of confirmed malaria cases was higher among men than women in Europe. 

Currently, a total of 107 studies are registered on Malaria in Europe with 13 studies ongoing in France. A clinical trial with Benjamin Ramarosandratana, MD as a principal investigator, was conducted at Pasteur Institute located in Paris, a health center specialized in infectious and tropical diseases. The center is also involved in HIV infection clinical research.

Chronic Myeloid Leukemia

The prevalence of chronic myeloid leukemia in France is predicted to reach levels of 24 per 100,000 in 2030. It is a cancer of the white blood cell characterized by the unregulated growth of myeloid cells in the bone marrow accumulating in the blood.CML usually affects middle-aged individuals and rarely children. 

A total of 1273 clinical trials are registered on worldwide on Chronic Myeloid Leukemia with 112 studies going on in France. Bordeaux Nord Aquitaine Polyclinic in France is conducting clinical trials on Chronic Myeloid Leukemia.

Cystic fibrosis

Cystic Fibrosis is a genetic disorder that causes severe damage to the lungs and digestive system. It is characterized by abnormalities affecting certain exocrine glands of the body especially those that produce mucus. Symptoms result due to thick and sticky mucous secretion pertaining to loss of lubricant action. It most commonly occurs in adults and affects around 7000 patients in France.

A total of 186 clinical trials are registered on Cystic fibrosis in France. Clinical trials on Cystic fibrosis were performed at centers like Necker hospital, a teaching hospital favored by proximity to clinical services, the presence of children and adult patients, and the involvement of physicians in the clinical units of research.

Rare disease & sites in Italy 

Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is the most common neurodegenerative disease of the motor neuron system. It affects the nerve cells in the brain and spinal cord responsible for controlling voluntary muscle movements. The main symptom is muscle weakness. ALS affects around 3 people out of 100,000 in Italy. Approximately 10 percent of all cases of ALS are familial.

Currently, 230 clinical trials are registered on ALS in Europe with 60 ongoing trials in Italy. Nemo Clinical Centers located in Italy has been performing clinical trials on neuromuscular diseases. Each site of the Nemo Clinical Center operates under an agreement with the National Health System.

Bone Cancer

Osteosarcoma is a type of tumor that affects the bones. Osteosarcoma can affect people at any age, but it is the most common bone cancer affecting children and adolescents under the age of 20. A total of 82 studies are registered for bone cancer on in Italy.

A number of trials on bone cancer were performed at Rizzoli Orthopedic Institute located in Bologna, Italy. It conducts research studies for the well-being of patients with musculoskeletal diseases.

Rare disease & sites in the United Kingdom 

Nasopharyngeal Cancer

Nasopharyngeal cancer is a rare type of cancer that begins in the upper part of your throat, behind the nose. The exact cause of nasopharyngeal cancer is not known. It gets difficult to recognize as symptoms are often similar to other less serious conditions. In the UK, about 250 people are diagnosed with nasopharyngeal cancer each year.

Currently, a total of 683 studies are registered on Nasopharyngeal cancer worldwide with 9 ongoing studies in the United Kingdom. A nasopharyngeal cancer clinical trial was performed at centers like Velindre Cancer Centre. It has participated in over 200 national and international clinical trials and has experienced cancer clinicians.

Hodgkin’s Lymphoma

Hodgkin’s Lymphoma is cancer that affects the tissues and lymph nodes of the lymphatic system. It limits the body’s ability to fight infection as a part of the body’s immune system is compromised. The first sign is a swollen lymph node and often a lymph node in the neck is affected. There are around 2,100 new Hodgkin lymphoma cases in the UK every year, accounting for less than 1% of all new cancer cases. 

Leeds Cancer Center located in England has performed clinical trials on Hodgkin’s Lymphoma. It was ranked as the 4th highest recruiting NHS Trust in the Nation for clinical research as it has recruited over 53,000 patients into clinical trials.

Rare disease & sites in Germany

Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare disease characterized by high blood pressure in the arteries of the lungs. The exact cause of PAH is not known and usually affects women between the ages of 30-60. Although treatable, there is no known cure for the disease. Individuals having mild symptoms may go years without a diagnosis.

A total of 176 clinical trials are registered on PAH in Germany. The majority of the Clinical trials on Pulmonary Arterial Hypertension in Germany were performed at the Centre for pulmonary hypertension, Thoraxclinic.

Haemophilia A

Hemophilia is a genetic disorder characterized by prolonged bleeding due to factor VIII or IX deficiency. Haemophilia A usually affects males and occurs in approximately 1 in 5,000 males. A total of 637 clinical trials are going on worldwide with 129 trials ongoing in Germany. Rare disease clinical trial sites such as Dr. v. hauner Children’s Hospital have been working on Haemophilia A.

Rare disease & clinical trial sites in the Asia Pacific and other regions

Rare disease & sites in Japan

Biliary Cancer

Biliary Cancer is a rare disease in which cancerous cells form in the bile ducts. Symptoms of biliary cancer include jaundice and pain in the abdomen. Colitis or certain liver diseases can increase the risk of cancer. More than 11,000 cases of biliary cancer have been registered to date in Japan.

Currently, a total of 334 clinical trials are registered with 28 studies ongoing in Japan. Clinical trials on biliary cancers are performed at centers like Osaka Medical Center in Japan

Rare disease & sites in Australia

Small Cell Lung Cancer

Small Cell Lung Cancer (SCLC) is an aggressive form of lung cancer, commonly caused by smoking. It is characterized by the uncontrolled growth of certain cells in the lungs. In the early stages of the disease, there may be no symptoms or mild symptoms. As the tumor grows, more signs develop like hemoptysis, shortness of breath, chest pain, etc. It is estimated that lung cancer will remain the most common cause of death in Australia.

A total of 978 clinical trials are registered on small cell lung cancer with 35 studies ongoing in Australia. Clinical trials on SCLC were performed at Border Medical Center, recognized as a leading center in multidisciplinary cancer care in Australia.


A mesothelioma is a form of cancer in the mesothelium, a protective lining on the inside of body cavities. Australia has the highest incidence rates of mesothelioma in the world. On average, 2 people are diagnosed with mesothelioma in Australia each day. Males are more likely to be diagnosed and the average time between diagnosis and death is around 11 months according to the Australian Institute of Health and Welfare (AIHW). 

It is generally accepted that the primary cause is exposure to asbestos and symptoms of mesothelioma typically appear 20–40 years after exposure to asbestos. It has one of the longest latency periods of all diseases. A total of 21 studies are registered for mesothelioma in Australia and sites like Chris O’Brien Lifehouse have performed clinical trials on mesothelioma. It is the largest cancer clinical trials unit in NSW with more than 100 clinical trials are conducted at any given time.

Rare disease & sites in India


Uveitis refers to inflammation of the middle part of the eye known as the uvea. This condition affects males and females equally. It occurs most often between the ages of 20 and 50. Symptoms include eye redness, pain, and blurred vision. The annual incidence of uveitis is estimated to be around 730 per 10000 in India. Currently, a total of 20 studies are registered 

On Uveitis. A number of Clinical trials on uveitis are performed at Aravind Eye hospital located at different places in India.

Sickle Cell Disease

Sickle cell disease is a hereditary and life-threatening rare condition characterized by the presence of sickle-shaped red blood cells in the bloodstream. It causes ongoing vascular damage and repeated injury to blood vessels and organs. Common symptoms associated with SCD include bone pain, chest pain, severe infections, anemia, etc. 

Currently, 763 clinical trials are registered on Sickle cell disease and Novartis investigative sites in India are performing clinical trials on Sickle cell disease.

Rare disease & sites in Korea

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder characterized by the thickening of tissue within the lungs. The initial, characteristic symptom is shortness of breath. Prevalence was estimated more in Korean males than females. A total of 366 clinical trials are registered on IPF with 19 studies are ongoing in South Korea. Clinical trials were performed at centers like Samsung Medical Center.

Rare disease & sites in China

Juvenile Arthritis

Juvenile arthritis is a chronic rheumatic disease of childhood, affecting approximately one per 1000 children. It causes joint inflammation and stiffness and occurrence is more common in girls. Currently, 8 studies are registered in China on Juvenile Arthritis. Clinical trials on Juvenile Arthritis are being performed at centers like Shanghai Children’s Medical Center located in shanghai, China.

Rare disease & sites in Taiwan

Idiopathic Thrombocytopenic Purpura

Idiopathic Thrombocytopenic Purpura (ITP) occurs most frequently in children and young adults. It is a blood disorder characterized by thrombocytopenia, abnormal bleeding into the skin, and mucous membranes. Incidence rates of ITP in Taiwan are close to western countries. A total of 7 clinical trials are registered on ITP in Taiwan from 293 clinical trials worldwide. Clinical trials on idiopathic Thrombocytopenic Purpura were performed at Chung-Ho Memorial Hospital in Taiwan.

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