Vol.:(0123456789)

The Patient - Patient-Centered Outcomes Research (2024) 17:25–37 

https://doi.org/10.1007/s40271-023-00648-5

ORIGINAL RESEARCH ARTICLE

Determining Commonalities in the Experiences of Patients with Rare 

Diseases: A Qualitative Analysis of US Food and Drug Administration 

Patient Engagement Sessions

Catherine Mease1  · Lewis J. Fermaglich1  · Karen Jackler2 · Shawn Shermer3 · Kathleen L. Miller1

Accepted: 26 September 2023 / Published online: 13 October 2023

This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

Abstract

Background Rare diseases are estimated to afect more than one in ten Americans. However, most patients with a rare disease 

face signifcant emotional, physical, and social challenges. To better understand the burden of disease and unmet needs, the 

US Food and Drug Administration (FDA) conducts and supports multiple patient engagement platforms. We analyzed summaries from these discussions to identify commonalities among patients with disparate rare diseases, the results of which 

could inform priorities for cross-disease policies and medical product development.

Methods We conducted a qualitative analysis of patient engagement session summaries to investigate shared experiences 

across rare diseases. Cross-disease similarities were identifed within four dimensions: product development/regulatory, clinical/physical, social/psychological, and economic/fnancial. Summaries from 29 rare diseases were included in our analyses.

Results Within the product development/regulatory dimension, we observed that patients and caregivers across rare diseases 

shared the desire for development of medical products that cured their disease or improved their overall quality of life. In 

the clinical/physical dimension, we found that patients had numerous common symptoms, including pain and fatigue. In the 

social/psychological dimension, we observed signifcant negative impact on mental health. Within the economic/fnancial 

dimension, patients and caregivers shared that disease burden caused signifcant fnancial hardships.

Conclusion We found remarkable similarities among patients with rare diseases across all four dimensions. Our results 

indicate that, even among rare diseases with diverse etiologies, patients share numerous commonalties due to their diseases: 

a lack of efective treatment options, certain physical symptoms, mental health challenges, and fnancial concerns.

1 Introduction

Listening to patients’ concerns and preferences is foundational for both healthcare delivery and medical product 

development. The patient perspective brings ideas and the 

potential for innovation that can assist healthcare providers 

and medical product developers in designing guidelines 

and creating drugs, biologics, and devices that can provide 

a meaningful diference to patients’ lives.

This is especially true for rare diseases. In the USA, a 

rare disease is defned as a disease with a prevalence of 

fewer than 200,000 people [1]. It is estimated that there 

are 7000–10,000 rare diseases, yet only approximately 

5% have an approved treatment [2, 3]. Additionally, for 

many rare diseases, little is known about the underlying 

pathophysiology or natural history, which is problematic 

for medical product development of drugs, biologics, and 

devices and establishing standards of care [4–7].

Given these challenges, determining similarities in 

patient experiences among disparate rare diseases could 

assist in establishing priorities for development of medical products and the development of treatment guidelines 

[8, 9]. To determine these commonalities, we analyzed 

summaries from two US Food and Drug Administration 

(FDA) patient engagement platforms designed to capture 

patient perspectives and amplify the patient voice directly 

to FDA and other stakeholders: (1) Patient-Focused Drug 

* Catherine Mease 

catherine.mease@fda.hhs.gov

1 Ofce of Orphan Products Development, Ofce 

of the Commissioner, US Food and Drug Administration, 

10903 New Hampshire Ave, Silver Spring, MD 20993, USA

2 Ofce of the Center Director, Center for Biologics Evaluation 

and Research, US Food and Drug Administration, 10903 

New Hampshire Ave, Silver Spring, MD 20993, USA

3 Patient Afairs Staf, Ofce of the Commissioner, 

US Food and Drug Administration, 10903 New Hampshire Ave, 

Silver Spring, MD 20993, USA
26 C. Mease et al.

Key Points for Decision Makers

Patients with diferent kinds of rare diseases shared 

signifcant burdens due to pain, fatigue, mental health 

concerns, and fnancial difculties.

Common issues voiced by patients sufering from various rare diseases suggest there are potential opportunities for medical product development and care management strategies to address these shared concerns in rare 

diseases.

Development (PFDD) meetings (created as part of the ffth 

reauthorization of the Prescription Drug User Fee Act in 

2012) and (2) Patient Listening Sessions (PLS) (created as 

part of ongoing FDA initiatives to incorporate the patient 

voice into the work of the agency in 2018) [10–12].

Topics addressed in patient engagement sessions 

include the symptoms, impacts of the disease on daily life 

(including employment, socializing, and hobbies), treatment experiences, beneft-risk assessment of therapies, 

and ideals for future drug development. Additionally, caregivers also shared their experiences in some sessions. 

While PFDD and PLS meetings are held for both rare and 

common diseases, this research focuses solely on those 

for rare diseases.

PFDD meetings function specifcally to provide a platform for both patients and caregivers to share the most 

signifcant symptoms impacting their daily lives, as well 

as their opinions of current approaches to treatment. The 

primary goal is to ensure the incorporation of the patient 

experience into drug development and evaluation. The 

target audience for these sessions includes medical product developers, researchers, as well as FDA staf [13]. 

PFDD meetings are led either by FDA (“FDA-led”) or 

by patient advocacy groups (“externally led”). After the 

PFDD meeting, a “Voice of the Patient” report is available 

online containing a summary of the dialog. There have 

been approximately 100 PFDD meetings held between 

2013 and 2022 [14].

PLS meetings focus on patients and caregivers rather than 

on specifc medical products and aim to provide patients 

with a platform to share their experiences and needs related 

to their health, disease, symptoms, and treatment preferences. The target audience is FDA staf members involved 

in medical product evaluation and review [15]. PLS meetings are hosted by the FDA Patient Afairs Staf and are 

considered either “patient-requested” or “FDA-requested,” 

depending on which group initiated the meeting. After PLS 

meetings, Patient Listening Session summaries are posted 

online. There have been approximately 50 PLS meetings 

held between 2018 and 2022 [14].

While both the PFDD and PLS sessions follow similar 

formats, dialogs may be framed diferently. The FDA-led 

PFDD and FDA-requested PLS sessions may contain more 

FDA-specifc questions (e.g., regulatory, product specifc, 

etc.) for patients to answer. The externally led PFDD and 

patient-led PLS meetings are generally conducted by patient 

groups and include more general questions about lived experiences with a rare disease.

In this research, we used qualitative analyses of patient 

engagement sessions to determine commonalities among 

patients with diferent rare diseases [8]. Patient engagement 

sessions provide a unique opportunity to use qualitative 

research to identify similarities due to the in-depth dialogues 

of patients’ experiences and perspectives that they contain.

2 Methods

For our analysis, we used the most recently published PFDD 

and PLS rare disease session summaries as of 1 December 

2021. Selecting these session summaries provided a sample that included a variety of diseases and patient populations, while maintaining a manageable volume of material 

to analyze.

Our fnal sample included patient engagement session 

summaries focused on 29 different diseases (Table  1). 

There were fve externally led PFDD meetings, fve FDAled PFDD meetings, ten patient-led PLS, and nine FDArequested PLS. For a given disease, we included both adult 

and pediatric sessions if they were separately split. Both 

meeting types could include patients and caregivers. The 

PFDD summaries ranged from 23 to 93 pages in length. 

The PLS summaries ranged from 2 to 13 pages in length. 

The session summaries provided us with over 620 pages of 

data to analyze.

A qualitative analysis was performed using a series of 

iterative steps. First, four dimensions were predetermined for 

analysis: product development/regulatory, clinical/physical, 

social/psychological, and economic/fnancial. These were 

based on the authors’ prior knowledge of the themes present 

in these meetings, as well as the areas of interest for this 

research study [8].

The coding process was conducted using the qualitative 

analysis software ATLAS.ti 9. Keywords within the sessions were identifed and coded into one of the four dimensions. Keywords were defned holistically and included any 

word related to one of the four dimensions. Symptoms that 

frequently recurred in a session were only coded once to 

ensure that longer summaries did not bias the results. Lists 

of the keywords for each dimension were then analyzed to 
Determining Commonalities in the Experiences of Patients 27 Table 1 Description of FDA patient engagement sessions and rare diseases used in analysis (n = 29) Disease Disease description Meeting type Date Pages Acromegaly Endocrine disorder related to excessive growth hormone resulting in over- growth and large facial features Externally led PFDD 21/01/2021 93 p Adrenomyeloneuropathy Metabolic disorder related to damage to brain and spinal cord membranes resulting in spinal cord dysfunction Patient-led PLS 07/05/2021 6 p Alpha-1-antitrypsin defciency Pulmonary disorder related to low levels of alpha-1-antitrypsin resulting in emphysema and liver disease FDA-led PFDD 29/09/2015 33 p Childhood cerebral adrenal leukodystrophy Neurologic disorder related to the accumulation of fatty acids in the brain resulting in difculty walking and learning disabilities FDA-requested PLS 13/11/2019 3 p Cystic fbrosis (nonsense mutations only) Pulmonary disorder related to the body’s ability to clear mucus resulting in blocked airways and lung damage. This session focused on the 10% of patients with cystic fbrosis that do not beneft from currently approved therapies Patient-led PLS 15/07/2021 13 p Fabry disease Metabolic disorder related to the body’s ability to metabolize fat resulting in issues for the kidneys and heart FDA-requested PLS 04/12/2018 2 p Focal segmental glomerulosclerosis Nephrology disorder related to impaired kidney fltration resulting in kidney damage Externally led PFDD 28/08/2020 81 p Frontotemporal degeneration Neurologic disorder related to the progressive damage to nerve cells in the brain resulting in changes in behavior, mood, and memory Externally-led PFDD 05/03/2021 75 p Gastroparesis Gastroenterology disorder related to slowed emptying of food in the stom- ach that results in digestive symptoms such as nausea and feeling full FDA-requested PLS 02/12/2019 3 p Glycogen storage disease type 1 Metabolic disorder related to the inability to breakdown glycogen result- ing in enlarged liver and kidneys FDA-requested PLS 18/03/2021, 25/03/2021 5 p and 6 pa Guillain–Barré syndrome Neurologic disorder related to the infammation of nerves resulting in muscle weakness and sometimes paralysis Patient-led PLS 29/09/2020 12 p Hemophilia A and B Hematologic disorder that slows down the blood clotting process resulting in uncontrolled bleeding FDA-requested PLS 22/09/2014 2 p Hereditary angioedema Immunologic disorder related to the accumulation of fuid outside of blood vessels resulting in recurrent attacks of severe swelling usually involving the face, hands, and feet FDA-led PFDD 25/09/2017 31 p Homocystinuria Metabolic disorder related to the body’s inability to break down certain proteins resulting in vision issues, skeletal abnormalities, and blood clots Patient-led PLS 26/06/2020 7 p Hunter syndrome (mucopolysaccharidosis type II) Metabolic disorder related to the body’s inability to break down complex sugar molecules resulting in heart disease, joint problems, and enlarged internal organs FDA-requested PLS 04/02/2020 4 p Huntington’s disease Neurologic disorder related to the progressive breakdown of nerve cells the resulting in movement issues and dementia FDA-led PFDD 22/09/2015 23 p
28 C. Mease et al. PFDD patient-focused drug development meeting, PLS patient listening session aTwo sessions occurred because the adult and pediatric sessions were split bSplit into two sessions to account for diferent FDA questions Table 1 (continued) Disease Disease description Meeting type Date Pages Hypothalamic obesity Metabolic disorder related to damage in the hypothalamus resulting in extreme hunger and weight gain Patient-led PLS 22/10/2021 8 p Krabbe disease (globoid cell leukodystrophy) Neurologic disease related to the breakdown of the myelin sheath resulting in respiratory failure, loss of muscle control, feeding issues Externally led PFDD 29/10/2020 67 p Late onset GM2 gangliosidoses (e.g., Tay–Sachs and Sandhof diseases) Metabolic disorder related to the accumulation of gangliosides resulting in muscle weakness Patient-led PLS 15/01/2021 8 p Mastocytosis Hematologic disorder related to the abnormal accumulation of mast cells resulting in allergic reaction-type symptoms Patient-led PLS 28/09/2021 7 p Neuronopathic Gaucher disease Metabolic disorder related to a defciency in an enzyme that breaks down fats resulting in enlarged liver and spleen and anemia Patient-led PLS 09/09/2021 5 p Organ transplant Post-transplant management including preventing organ rejection, treating their underlying condition, and complications of immunosuppression FDA-led PFDD 27/09/2016 27 p Pemphigus pemphigoid Dermatologic disorder related to an overactive immune system resulting in lesions and blisters Patient-led PLS 08/02/2021 6 p Polyglutamine spinocerebellar ataxias and dentatoru- bal-pallidoluysian atrophy Neurologic disorder related to impaired nerve fbers resulting in move- ment and speech issues and epilepsy Externally led PFDD 25/09/2020 50 p Progressive multifocal leukoencephalopathy (PML) Neurologic disorder related to a virus destroying nerve cells in the brain resulting in movement and speech issues FDA-requested PLS 22/07/2020, 11/09/2020 5 p and 5 pb Sanflippo syndrome (mucopolysaccharidosis type III) Metabolic disorder related to a defciency in an enzyme that breaks down complex sugar molecules resulting in behavioral symptoms and demen- tia FDA-requested PLS 13/05/2019, 17/10/2019 3 p and 3 pa Smith–Magenis syndrome Neurologic disorder related to the body’s ability to produce proteins resulting in unique facial features, cognitive and sleep issues FDA-requested PLS 12/08/2020 6 p Systemic sclerosis Rheumatologic disorder related to the growth of connective tissue result- ing in thickening of the skin, but may also cause problems in the blood vessels, internal organs, and digestive tract FDA-led PFDD 13/10/2020 24 p Vascular Ehlers–Danlos syndrome Rheumatologic disorder related to the production and quality of collagen resulting in arterial, intestinal, and/or uterine fragility Patient-led PLS 07/10/2020 3 p
Determining Commonalities in the Experiences of Patients 29

observe common themes. The most frequently coded words, 

or groups of words, were interpreted into key themes via 

an iterative process between two of the authors (C.M. and 

K.L.M.) (Supplementary File) [16]. The key themes were 

compared with the original summary text that the words 

were pulled from to ensure accurate context [17]. The two 

authors also confrmed that the coded words were drawn 

from the summaries of multiple patients with rare disease 

engagement sessions, to ensure that each key theme was 

based on commonalities between numerous rare diseases. 

However, the key themes should not necessarily be interpreted to represent themes that were observed in all sessions, but rather themes that were common across multiple 

sessions.

3 Results

We analyzed the summaries from 29 patient with rare disease engagement sessions to determine the key themes in 

similarities among each of the 29 groups of patients with 

rare diseases who participated in these sessions across the 

four predetermined dimensions: product development/

regulatory, clinical/physical, social/psychological, and economic/fnancial. We found numerous unifying commonalties 

between patients across the 29 rare diseases within all four 

dimensions, despite the wide range of diseases studied. The 

full list of key themes within these four dimensions is listed 

in Table 2.

Table 2 Key themes: similarities in experience across rare disease patients

Dimensions Key themes

Patients and caregivers across rare diseases voiced:

Product development/regulatory The primary goal of therapy development is to fnd a cure

Secondary to fnding a cure, delaying disease progression or symptom management were equally important to 

patients

For new therapies, wanting to know if their quality of life will be improved on the new therapy; a primary 

concern is the side-efect profle

Frustration with the lack of treatment options available for their disease

Reluctancy to participate in a trial where they had the potential of receiving placebo (especially if they had to 

go of their current therapy regimen)

Frustration with access to clinical trials due to eligibility criteria limiting enrollment and the burdens of time 

commitment such as travel to trial sites

The inability to administer medication orally versus parenteral routes (e.g., injections) that are uncomfortable, 

painful, and risky

Clinical/physical Maintaining control of the disease symptoms is challenging

The most commonly reported symptoms were pain and fatigue/low energy

Secondary but frequently reported common disease symptoms included sleep disturbances, feeding issues 

(weight gain/loss, swallowing, and diet modifcations), gastrointestinal (nausea, diarrhea, and constipation), 

movement/mobility (walking, balance, and dexterity), and neurologic (cognitive, speech, and headache)

A correct and timely diagnosis is important to appropriately manage symptoms and receive treatments; a misdiagnosis or a lack of diagnosis prevents patients from controlling their symptoms and disease

Surgery is a frequent treatment modality (for some diseases) but not always successful

Social/psychological The physical and psychological toll of disease is a daily constant stressor

This toll leads to strained relationships with family, along with feelings of dependency

This toll also leads to diminished relationships with friends, along with feelings of isolation

Their mental health is also negatively impacted by the daily stress, worry, frustration, and fear due to disease 

burden and uncertainty

Economic/fnancial The ability to work is greatly impacted by disease burden

Losing the ability to work leads to challenges in fnancing treatments and care

Losing the ability to work leads to the loss of both health insurance and the ability to pay for care

Losing the ability to work also leads to patients or caregivers being forced into early retirement regardless of 

whether they are fnancially (and emotionally) ready to retire

The ability to gain timely and appropriate access to treatments is delayed due to insurance coverage limitations 

and prohibitive prices for treatments
30 C. Mease et al.

3.1 Product Development/Regulatory

3.1.1 Concerns for Quality of Life Pertaining to New 

Product Development

Patients primary goal with therapy development was to 

fnd a cure. They shared:

“He said he hopes and prays for a cure in his lifetime 

and would do anything for science so that maybe no 

one will have to endure what he has.” [Adrenomyeloneuropathy PLS]

“Some participants were more likely to prefer gene 

therapy because it gives them more hope for a cure as 

opposed to management of the disease.” [Childhood 

cerebral adrenal leukodystrophy PLS]

Besides fnding a cure, managing disease progression 

and controlling symptoms were key goals. A caregiver 

explained:

“I would say minimize symptoms. Obviously we 

would want her to live a long, productive life as anyone expects to, but we’ve seen our daughter sufer 

and we’ve seen the other side of Krabbe and defnitely to reduce those symptoms, reduce the side 

efects [of the disease] would be huge because I think 

that improves their quality of life.” [Krabbe disease 

PFDD]

We found that across all sessions, the improvement of 

quality of life was central to patients’ product development 

goals. A key issue patients shared was the negative impact 

that treatment side efects can have on their quality of life. 

As patients shared:

“Several participants expressed frustration with the 

extent of the side efects they experienced, including 

one participant who stated that her treatment regimen 

‘does not manage my symptoms, just causes them.’” 

[Organ transplant PFDD]

The development of more convenient routes of administration, such as oral, was also a commonly expressed 

perspective. They shared:

“Family hopes for a better treatment without needles.” [Neuronopathic Gaucher disease PLS]

3.1.2 Views on Clinical Trial Participation

Patients across all rare diseases emphasized the importance of continued research and development for their condition. However, some patients were reluctant to participate in placebo-controlled clinical trials, citing concerns 

with not receiving treatment during the study period. A 

common refrain heard was:

“More than half of caregivers and patients expressed 

uneasiness with placebo-controlled trials for PML. 

Some caregivers and patients believed placebo would 

waste valuable time and would defeat the purpose of 

treatment...” [Progressive multifocal leukoencephalopathy PLS]

Others discussed the importance of selecting medical product clinical trial endpoints that are meaningful to 

patients. As patients shared:

“Many participants shared their concern about the endpoints that are selected for clinical trials. As parents, 

they often see progress not measured in the clinical 

trials, including progress beyond cognitive function.” 

[Sanflippo syndrome PLS]

Many felt that the trial design did not take their daily lives 

into consideration. A patient stated:

“...I don’t know that people putting together these 

trials understand what a pain that is to do [24-hour 

urine tests] if you’re working or in and out of the house 

throughout the day.” [Focal segmental glomerulosclerosis PFDD]

Similarly, a commonality among patients with rare diseases was the signifcant burden imposed by travel to trial 

sites. Caregivers and patients shared:

“He had to travel from Dallas to Boston twelve times 

in two years to participate in a clinical trial, which 

was difcult physically and logistically.” [Adrenomyeloneuropathy PLS]

“Distance from where the patient/caregiver lives to the 

[trial] treatment center also determines how burdensome the visits are.” [Hemophilia A and B PLS]

3.2 Clinical/Physical

3.2.1 Controlling Disease

Managing numerous symptoms to help improve daily life 

is a key issue for patients with a rare disease. Despite the 

many medications required to control their disease, patients 

still feel that their symptoms are not efectively managed. 

Patients shared:

“Together, I am on over 30 medications. While they 

do provide some help and relief, I am nowhere close to 

where I was before acromegaly.” [Acromegaly PFDD]

“Patients indicated that their current medications 

sometimes make their symptoms manageable, but that 
Determining Commonalities in the Experiences of Patients 31

some of the current medications generally seem to lose 

efect after weeks to months of use.” [Gastroparesis 

PLS]

The inability to efectively control disease symptoms is 

a common experience for patients with rare diseases. Maintaining control of disease symptoms is a challenging experience for both patients and caregivers. Caregiver perspectives 

included:

“A majority of caregivers added that although patients’ 

needs may change with development, the level of care 

remains challenging and complex, requiring constant 

surveillance.” [Smith–Magenis syndrome PLS]

“All caregivers of GSD1a patients agreed that the 

symptoms were constantly changing, and it was a 

constant struggle to manage them. One participant 

described GSD1a as a ‘roller coaster ride.’ One participant described the burden of raising children with 

GSD 1a as ‘24/7.’” [Glycogen storage disease type 1 

PLS]

Some caregivers described other challenges, such as disease management in non-verbal patients and learning to use 

sophisticated medical equipment. A caregiver perspective 

included:

“[A caregiver] reported that when it became very 

difcult for her son afected by DRPLA to speak, he 

started to use an Eye Gaze [communication device], 

but ‘unfortunately because of his epilepsy and myoclonic movements, he can’t use that very efciently.’” 

[Polyglutamine spinocerebellar ataxias and Dentatorubal-Pallidoluysian atrophy PFDD]

3.2.2 Common Symptoms

The two most commonly reported symptoms by patients are 

pain and fatigue/low energy. Often patients experience pain 

and fatigue concomitantly. As patients shared:

“Pain and fatigue after [Guillain–Barré syndrome] 

recovery remain extremely burdensome to the community.” [Guillain–Barré syndrome PLS]

Descriptions of pain symptoms were provided by patients. 

They shared:

“I wake up every morning in acute pain and until my 

pain meds kick in, I am unable to function.” [Mastocytosis PLS]

“I have birthed two babies without epidurals, and I 

have actually had a kidney stone, so I do have a high 

tolerance for pain...and this pain [hereditary angioedema abdominal attack] is above 10 on the pain 

scale...During these attacks, I can’t eat, I can’t drink, 

you basically vomit every little bit that is in you.” 

[Hereditary angioedema PFDD]

“...pain that is indescribable. It is almost like a nerve 

pain as well as if you got a little blow of air on it, it is 

excruciating.” [Systemic sclerosis PFDD]

Patients described how the fatigue symptoms make them 

feel. They shared:

“On really bad days, it feels like I’m kind of pushing 

through mud to get everything done, and I don’t often 

have much energy left by the end of the day.” [Focal 

segmental glomerulosclerosis PFDD]

“Several participants described experiencing constant fatigue, tiring easily, or feeling a general lack 

of energy. One participant stated that ‘on the worst 

days... I can barely get out of bed.’” [Organ transplant 

PFDD]

Secondarily, but frequently reported, common rare disease symptoms included food/feeding issues (weight gain/

loss, swallowing, and diet modifcations), gastrointestinal 

symptoms (nausea, diarrhea, and constipation), movement/

mobility issues (walking, balance, and dexterity), neurologic 

symptoms (cognitive, speech, and headache), and sleep disturbances. Patients experience many of these symptoms 

together as they shared:

“Development of treatments that are safe for those with 

VEDS for other struggles, such as gastrointestinal pain, 

dysmenorrhea, hormone therapy, menopause, musculoskeletal pain, are also considered vital to the people 

who spoke during this call to help improve quality of 

life.” [Vascular Ehlers–Danlos syndrome PLS]

Although participants had difering diseases, they shared 

common symptoms and the desire for greater control over 

them.

3.2.3 “The Diagnostic Odyssey”

A correct and timely diagnosis is vital to appropriately manage symptoms and receive treatments. A misdiagnosis or a 

lack of diagnosis prevents patients from controlling their 

symptoms and may lead to further progression of disease. 

Patients shared their time-consuming experiences of visiting numerous doctors before obtaining a correct diagnosis, 

in some instances waiting decades for a correct diagnosis. 

One patient shared his nearly 30-year diagnostic journey:

“I am 55 years old. I was diagnosed in 2014 at age 

48...” [Late onset GM2 gangliosidoses PLS]
32 C. Mease et al.

Many others shared similar experiences and spoke of 

delayed treatments due to a diagnosis later in life as well 

as the impact on patients’ quality of life. Caregivers stated:

“Some caregivers emphasized the importance of early 

testing for MPS II, reasoning that early diagnosis has a 

signifcant impact on patients’ quality of life.” [Hunter 

syndrome PLS]

We found that lengthy diagnostic journeys also negatively 

impacted the relationship between the patient and their care 

team. As patients stated:

“The overarching theme here was frustration with 

medical care, including the feelings of being treated 

like a hypochondriac, confusion among medical professionals of [Vascular Ehlers–Danlos syndrome] 

with other non-life-threatening conditions, not being 

taken seriously in emergencies, and the fear of dying 

in the emergency department waiting room.” [Vascular 

Ehlers–Danlos syndrome PLS]

“Some wrote about difculty getting diagnosed, and 

one expressed the emotional impact of ‘being made 

out to be a hypochondriac by multiple doctors, nurses, 

and staf.’” [Systemic sclerosis PFDD]

Constant misdiagnoses resulted in clinical and emotional 

consequences for patients and caregivers.

3.3 Social/Psychological

3.3.1 Disease Burden on Mental Health

A central commonality was that the burden and uncertainty 

of their rare disease causes signifcant stress, worry, frustration, and fear, all of which have severe negative impacts on 

the mental health of patients. As patients reported:

“Another speaker shared the crippling anxiety that 

[cystic fbrosis] has caused him, detailing his fears of 

not being able to breathe, that his lungs will eventually lose their function, and that he will end up in the 

hospital.” [Cystic fbrosis PLS]

“Another participant shared that the ongoing worsening of symptoms and feeling ‘that I would never get 

better’ led to signifcant depression.” [Huntington’s 

disease PFDD]

We found that patients across the diseases feel that the 

impact on their mental health is among the worst aspects of 

the disease. Patients shared:

“Through all of this [hereditary angioedema symptoms], the other most debilitating symptom is mental 

health...I sufer with depression; I sufer with anxiety.” 

[Hereditary angioedema PFDD]

“[Hypothalamic obesity] is described as a “living hell” 

because the [patient] cannot go unsupervised, it creates toxic family dynamics, puts a strain on marriages 

and sibling relationships, creates isolation and there 

is little support available to caregivers or survivors” 

[Hypothalamic obesity PLS]

Patients shared they felt they were not receiving the mental health resources they need. One patient stated:

“There’s a big mental health component to Acromegaly that needs to be acknowledged...I desperately 

would have needed access to mental health resources, 

but no one thought about providing those to me.” 

[Acromegaly PFDD]

3.3.2 Impact on Relationships

The physical and mental toll of their disease often forces 

patients to depend on their family for help with daily needs. 

Patients and caregivers explained:

“What worries me most is the loss of my independence 

and inability to care for myself and to be an active 

participant with my family.” [Alpha-1-antitrypsin defciency PFDD]

“Parents expressed their worry about losing the ability to care for their child at home, either because of 

the child’s condition becoming too severe or because 

of the parent becoming sick, injured, or aged.” [Polyglutamine spinocerebellar ataxias and DentatorubalPallidoluysian atrophy PFDD]

Others elaborated on this theme, sharing that not knowing when the loss of independence would manifest created 

additional stress. Caregivers also struggle with patients losing their independence. A patient shared:

“It’s very difcult and the spouse, or the mate, or the 

partner all of a sudden has to take the slack out and 

it can be a very difcult strain on the relationship or 

the marriage.” [Alpha-1-antitrypsin defciency PFDD]

Disease burden also afected relationships with friends. 

The decreased ability to socialize and attend activities with 

friends due to their disease leads to feelings of isolation. A 

patient discussed:

“The isolation of the disease has made my dogs my 

best friends, and my true friends I had don’t call anymore. People just don’t know what to do with me.” 

[Frontotemporal degeneration PFDD]

These feelings of isolation are compounded by the rarity 

of disease, as it is often difcult for others to comprehend 

what patients are experiencing. For example:
Determining Commonalities in the Experiences of Patients 33

“Homocystinuria is isolating because most people 

have not heard of it nor do they comprehend the metabolic complexities of the disease. Rarely do others take 

the time to understand the disease and what it takes to 

manage it.” [Homocystinuria PLS]

“Another caregiver described that many of her daughter’s friends have ‘faded away. People are uncomfortable seeing her like this. [She’s] not the friend they 

remember.’” [Huntington’s disease PFDD]

3.4 Economic/Financial

3.4.1 Losing the Ability to Work

A key issue for patients with rare diseases was the ability to 

continue working. Symptoms often interfere with the ability to complete a full day of work. For example, a caregiver 

shared:

“My mother took a job at a local retailer. For the frst 

time in her life, she quit a job when she was unable to 

retain any of the training. She was humiliated, and her 

confdence was crushed.” [Frontotemporal degeneration PFDD]

The ability of patients to complete their workday is often 

disrupted not only by the symptoms of their disease, but by 

the disease treatments as well. As patients shared:

“[Saying infusing my medication has] been disruptive 

to my work schedule is just about the biggest understatement possible. My infusion from beginning to 

end [including travel time] takes a pretty hefty time 

slice out of my day.” [Alpha-1-antitrypsin defciency 

PFDD]

“Another [patient] described how he could no longer 

pilot an airplane according to FAA guidelines due to 

the dose of prednisone he had been prescribed.” [Pemphigus pemphigoid PLS]

The disruption to their workday may contribute to loss 

of employment, which can result in loss of both income and 

health insurance coverage. Patients and caregivers shared:

“Patients/caregivers shared that they are concerned 

about the fnancial burden of treatment. It is especially 

worrisome to patients who are unable to work, do not 

have insurance, or are unable to receive disability benefts.” [Fabry disease PLS]

Another concern was patients being able to fnd a job 

when living with a rare disease. Patients and caregivers 

shared:

“As I started to look for another job, I wondered what 

I would tell prospective employers – ‘Yes I have 25 

years of experience, but on random days I need to 

completely shut down; at every meeting I will need 

to get up and walk around for 20 minutes because of 

swelling and pain, I can’t really travel due to my low 

immune system and risk of stroke, and the commute 

to the ofce is too long so I will need to work from 

home permanently!’ This was not going to be easy. 

But I had to try – I need the health insurance for all the 

expensive of-label treatments I would need.” [Focal 

segmental glomerulosclerosis PFDD]

“One caregiver talked about how their child(ren) was 

concerned about not being able to pursue the job or 

career they are interested in [due to disease burden].” 

[Glycogen storage disease type 1 PLS]

Due to the need for full-time care at home, many caregivers must leave their jobs as well. A caregiver shared:

“We have forgone possible career opportunities. And 

many parents ended up quitting their jobs to make sure 

their child has the care they desperately need. And in 

our case [he] has spent the last 10 years, essentially out 

of the paid workforce to provide consistent in-home 

care.” [Krabbe disease PFDD]

Losing the ability to work forces patients into early retirement, regardless of whether they are fnancially (or emotionally) ready to retire. A caregiver shared:

“He could no longer walk so he retired a second time.” 

[Adrenomyeloneuropathy PLS]

3.4.2 Insurance Limitations

The ability to gain timely and appropriate access to treatments can be delayed due to limitations in insurance coverage and prohibitive prices for treatments. Patients discussed 

frustration due to denial of coverage for of-label uses of 

medications. A patient shared:

“At one point I was using more than 10 epi [epinephrine] auto-injectors each month and my insurance 

would only allow 2.” [Mastocytosis PLS]

We found that patients shared similar experiences of 

delayed treatment due to limits on insurance coverage.

4 Discussion

In this study, we qualitatively analyzed FDA patient engagement sessions for 29 rare diseases and identifed numerous 

commonalities among patients across four study dimensions.

First, we fnd that patients universally voice that life with 

a rare disease is overwhelmingly uncertain. This uncertainty 
34 C. Mease et al.

extends to all four dimensions: from concern over whether 

treatments will be efective to limitations on the patient’s 

ability to engage in socializing and work due to disease burden. This uncertainty translated into a substantial burden on 

mental health.

Signifcant anxiety and depression, related to the impact 

of their disease on daily life, was reported by patients in 

almost all sessions studied. Additionally, many patients 

shared that they are not receiving treatment for their mental 

health. For example, multiple patients across diferent diseases discussed problems with accessing a therapist, particularly one that understood their unique needs [18].

To alleviate these issues, prioritization of mental health 

care should be included in treatment plans for patients with 

rare diseases [17, 19, 20]. While there are multiple ways 

that this could be implemented, one avenue is to ensure that 

patient organizations and rare disease Centers of Excellence 

provide mental health resources [21, 22]. For example, while 

Centers of Excellence aim to provide patients with multidisciplinary care and determine best practices for treatment 

and research, a brief review of the websites of many of these 

centers did not fnd mental health resources. A frst step in 

addressing this disparity could be adding mental health 

resources, such as for rare disease therapists or community 

support groups, onto these websites.

Second, despite the difering etiologies of the rare diseases studied, we found patients reporting many of the same 

symptoms. Perhaps unsurprisingly, many were related to the 

nervous system (e.g., pain, fatigue, sleep, headache), which 

are relatively poorly understood both scientifcally and clinically [23–25]. This suggests that there may be opportunities for future medical product development that addresses 

symptom management in this area irrespective of disease. 

Additionally, it implies that signifcant advances in understanding these symptoms in one disease may have larger 

implications for patients of other, seemingly unrelated, diseases [26]. As a starting point, collaborative rare disease 

data sharing platforms should consider using these common 

symptoms as a basis for the initial data felds being collected 

[27].

Third, we also fnd that patients with rare diseases want 

more involvement in the medical product development process. For example, patients want to be involved in clinical 

trial design, such as the selection of patient-meaningful 

study outcomes [28, 29]. Patient involvement in endpoint 

determination is important because patients with rare diseases have unique insights into their most important symptoms [30, 31]. For example, patient input from a PFDD 

meeting for progressive familial intrahepatic cholestasis 

(a gastroenterology disorder related to the liver’s ability to 

secrete bile) was used to identify “itch” as a primary endpoint in a drug clinical trial [32].

Considering the patient perspective in the medical product development process may inform more protocols that are 

more accessible and with more meaningful results [33–35]. 

In fact, the 21st Century Cures Act (“Cures Act”), signed 

into law in 2016, requires the FDA to consider the impact 

of diseases on patients’ lives and “patient preferences with 

respect to treatment of such disease” in the drug development and review process, including the assessment of riskbeneft evaluations that inform regulatory decision making [36, 37]. Internationally, the Council for International 

Organizations of Medical Sciences (CIOMS) has released 

a report describing how PFDD-style meetings have helped 

to incorporate the patient voice in medical product development in the European Union and Japan [38].

The Cures Act also required the FDA to create a PatientFocused Drug Development Guidance series. In this series 

of publicly available documents, the FDA provides a roadmap for industry and other stakeholders to recognize the 

patient voice, including ways to add patient-focused outcome measurements to clinical trials [39]. In addition to the 

patient engagement sessions utilized in this research, the 

FDA also provides other avenues for patients to interact with 

the FDA. This includes a Patient Engagement Collaborative, 

a Patient and Caregiver Connection program, and a Patient 

Representative Program [40–42]. Additionally, patient representatives are involved in the review process of rare disease grant applications submitted to FDA’s Ofce of Orphan 

Products Development.

While the FDA seeks to incorporate the patient voice into 

product development and review where possible, additional 

actions can be taken by other stakeholders. For example, 

medical product developers can seek FDA input early in the 

medical product development process to discuss the use of 

patient experience data [43]. In addition, medical product 

developers may also seek patient input in the early phases of 

development to identify clinical outcomes for trials [16, 44].

Finally, we fnd that patients and caregivers reported a 

signifcant economic burden due to the costs of living with 

a rare disease. Patients disclosed signifcant fnancial costs 

of living with a rare disease, including expenses from hospitalizations and medical treatments and equipment [45, 46]. 

However, the largest reported factor contributing to fnancial 

uncertainty for patients and caregivers was the limited ability or inability to work due to disease burden. These diffculties were partly due to the extreme challenges in living 

with or caring for a patient with a rare disease that have been 
Determining Commonalities in the Experiences of Patients 35

previously identifed: daily symptom management, time 

requirements for treatments, and mental health challenges. 

Losing the ability to work, working less than full-time, or 

unwanted early retirement causes fnancial difculty due to 

a loss in income, and, in the US, loss of health insurance tied 

to employment [47].

4.1 Limitations

There are several limitations that restrict the generalizability of our analysis. First, we can only analyze patients who 

participate in the patient engagement sessions. This limits 

our analysis to patients who possess the resources (e.g., time, 

awareness) and ability to engage in these sessions.

Second, patient engagement sessions are public platforms 

with only limited anonymity for patients when sharing their 

perspectives. Participants in the patient engagement sessions 

may not feel comfortable disclosing some topics in a public 

forum, such as suicidal ideation, reproductive health, or the 

impact of the disease on sexual intimacy. These types of personal and private topics may not be accurately represented 

in our results. However, it should be noted that participants 

are able to make diferent types of anonymous comment 

submissions that can be included in the summaries, which 

could mitigate this limitation.

Third, the FDA does not collect demographic data of 

participants in the patient engagement sessions, and therefore we cannot provide these data in the manuscript. While 

eforts are made by the FDA and patient groups to recruit 

diverse patient perspectives for the engagement sessions, the 

dearth of quantitative demographic data limits our ability to 

predict the generalizability of the study.

Finally, the scope of the results of the economic/fnancial 

dimension may be limited since these issues were not the 

focus of the patient engagement sessions, unlike the other 

dimensions.

5 Conclusion

In this research, we sought to understand whether patients 

with disparate rare diseases shared any similarities across 

four dimensions: product development/regulatory, clinical/

physical, social/psychological, and economic/fnancial. A 

qualitative analysis of summaries from FDA patient engagement sessions for 29 diferent rare diseases provided key 

themes for each dimension, and we found signifcant commonalities. These include similarities in clinical symptoms 

such as pain and fatigue, as well as signifcant, unaddressed 

mental health concerns. Commonalities in the patient perspective can help improve patient care across rare diseases, 

with implications for the medical product industry, health 

systems, and health plans.

Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s40271-023-00648-5.

Acknowledgements The authors would like to thank Sandra Retzky 

for her input on this research project.

Declarations

Funding This project was supported in part by an appointment to the 

Research Participation Program at the US Food and Drug Administration administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of 

Energy and the US Food and Drug Administration.

Conflict of interest The authors declare that they have no conficts of 

interest.

Disclaimer This manuscript refects the views of the authors and should 

not be construed to represent FDA’s or the Department of Health and 

Human Services (HHS)’s views or policies.

Availability of data and material Session summaries analyzed in the 

manuscript can be found on the FDA’s website for condition-specifc 

meeting reports and other information related to patients’ experience 

(https://www.fda.gov/industry/prescription-drug-user-fee-amendments/

condition-specifc-meeting-reports-and-other-information-related-patie

nts-experience).

Ethics approval The FDA institutional research board (IRB) found this 

study exempt from IRB review.

Consent to participate Not applicable.

Consent for publication Not applicable.

Code availability The codes generated and analyzed for this study are 

available from the corresponding author.

Author contributions K.L.M. conceived the study. C.M., L.J.F., 

K.J., S.S., and K.L.M. designed the study. C.M. and K.L.M. collected, analyzed, and interpreted the data. C.M. and K.L.M. drafted 

the manuscript. L.J.F., K.J., and S.S. provided substantive edits to 

the manuscript. All authors read and approved the fnal version of the 

manuscript.

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