Patient-reported outcomes: Time for a new approach?

By Janice Abbott

Patient-reported outcome (PRO) measurement (e.g. health-related quality of life questionnaires, symptom diaries) can provide a standardized, valid and reliable way of gaining the patients’ perspective on ‘how they are’ or the benefits and limitations of a specific intervention. The insights that patients have concerning their health are important given that aspects of patient-reported quality of life are independent predictors of survival in cystic fibrosis (CF) [1]. Regulatory authorities require the inclusion of PROs in clinical trials as an additional outcome parameter and PRO information is becoming important in labelling claims. It is noteworthy that the top 10 research questions, reached by global consensus of patient and healthcare providers, all require the inclusion of CF-specific PROs to achieve meaningful answers [2]. This represents a significant paradigm shift but capturing data that matters to patients, families and clinicians is challenging. Two of the persistent challenges in CF PRO measurement are a) the development and use of technologies to enable efficient administration, accurate scoring, and the correct interpretation of data and b) being able to accurately measure PROs (or parental proxy assessment) across the entire CF lifespan. These important issues are considered by two papers in this issue of the Journal of Cystic Fibrosis [34].

PRO measurement largely remains a research endeavour with little uptake in clinical practice. Administering, scoring and interpreting PROs in a busy clinic is difficult. It requires staff time and expertise and the results are not instantly accessible to steer a discussion with the patient or to aid clinical decision making. Paper-based data collection suffers from missing, unreadable data that is prone to scoring/mathematical error. The development of electronic PRO (ePRO) technologies is immensely important in clinical practice and for endpoint assessment in clinical trials. It is a cost-saving, patient-friendly approach to PRO assessment: data collection can occur in clinic, the patient’s home, workplace or school. Results can be added to a patient’s electronic medical file, alerts triggered by problematic scores and clinicians can track patient/parent-reported symptom/event data over time. Importantly, electronic data capture enhances the integrity and accuracy of the data, makes it logistically easier to collect repeated assessments (daily or at several points over a trial), and is preferred over paper-based data collection by the US Food and Drug Administration (FDA).

There is growing evidence that paper and electronic versions of PROs typically provide comparable data but this requires psychometric evaluation if transferring an original paper-based questionnaire to an electronic mode of administration. Solé and colleagues have demonstrated measurement equivalence with paper and electronic administrations of the Cystic Fibrosis Questionnaire-Revised (CFQ-R teen/adult version) [3]. The e-CFQ-R web version is linked to an online database that can be adapted for any electronic devise (smartphone, tablet, computer). Immediately the patient completes the questionnaire, results are sent to the healthcare team and the data are saved in a centralized, protected database. Real-time patient-reported data are available to the clinician as an adjunct to clinical data. Access to the English and Spanish versions are by independent web addresses provided in the paper. Ultimately, the integration of PRO data within electronic care records as developed by Peckham et al. [5], or in CF patient registries would enable efficient patient care and longitudinal research endeavours.

There is a lack of PROs that can be used as endpoints in early intervention studies in CF. Such instruments are time-consuming and painstakingly difficult to develop so the research of Edwards et al. reporting on the initial development of a CF-specific, parent-reported instrument for children 0–11 years is welcome [4]. The need for an effective way of data collection is also considered. The instrument takes the form of an electronic (web-based data capture), observational sign/symptom diary containing 17 respiratory and activity signs that parents report the presence or absence of. Results suggest that children aged 7 to 11 years are best reporting for themselves, therefore observational reporting by parents should focus on young children aged 0 to 6 years. Considerable evaluation has yet to determine the final instrument but the development of the scale follows FDA guidance enabling its acceptance as a clinical trial endpoint in infants and young children with CF.

Over the last twenty years we have learned a great deal about measuring patient-reported outcomes in CF, and there are many pitfalls when employing PROs in CF trials [6]. They are typically secondary endpoints and the trial is not powered on them, often making it difficult to draw valid inferences about treatments. However, there are trials that have collected patient-reported respiratory symptom data as the primary endpoint [78], employing the only CFQ-R subscale that has been approved by the FDA for use as an endpoint. Scientific, regulatory and pragmatic factors are driving the shift towards ePRO data collection. The development of ePROs is not trivial, yet they are fast becoming the ‘gold standard’ for PRO data capture in clinical trials. The challenge now is to develop CF-specific, lifespan PROs, utilising new technologies that can deliver real-time, high-quality PRO information. They also need to be acceptable to the regulatory bodies to aid their decisions on cost-effectiveness and ensure the appropriate commissioning of new medicines to improve the lives of people with CF and their families.

Original article with references here.

Freedom!

Guest post by: Kathy Russell

Today was a terrific day! We have just experienced a three-day series of high temperatures in the 80s. In the middle of summer that would be quite normal, but getting that kind of weather in April is extremely rare in my part of Oregon. I made the most of those days.

In our front yard, we have a very old and very large black walnut tree. There is a brick planter built around the base of the tree and there are various plants, including several sword ferns, growing in it. The sword ferns are beautiful if they are properly groomed. Each year, when the weather permits, I get out and cut away all of the old fronds to make room for new growth.

I didn’t get to do that last year because of my health. I just didn’t have the energy to do the bending and twisting that the task entails. Also, since I am on continuous oxygen, it makes getting out to the tree a bit problematic. Dragging my portable oxygen concentrator (POC) while I am pruning the ferns is a bit of a pain. I bend over and cut some old fronds, then I have to stand up and drag the POC to my next position. It makes it more of a chore and a lot less fun than it used to be before I was on oxygen.

Yesterday I worked on a couple of ferns that I could reach with the length of hose that is on my big concentrator. That was fairly workable, but I couldn’t go beyond the range of my hose. Also, I couldn’t reach two of the ferns. After about an hour I was getting too hot and decided to stop working on a large fern that was at the end of my tether.

Today, my husband took my large concentrator outside and plugged it into an outdoor outlet. With the 75 feet of hose that I have on it, I had a lot of freedom to move around. I was able to finish the fern that I left yesterday and finish the final two. I didn’t have to worry about running out of hose length and I felt so unencumbered. It was so great to be able to move around like a normal person. I absolutely loved that feeling of freedom. It was almost like not even being on oxygen.

My oxygen saturation stayed in a very good range and I got a couple of hours of fresh air. I was mostly in shade so I didn’t have to worry about being in the sun too long. Having the ability to move around and not have to drag a POC was a real gift as far as I am concerned.

CYSTIC FIBROSIS WIND SPRINT 66: CIRCUIT TRAINING 1

For people with cystic fibrosis, getting “back” into shape is a common occurrence. Because of the nature of the disease, patients often experience set backs in both their health and fitness routines. But, exercise is an important and essential part of remaining compliant with treatments and medications in order to live a longer, healthier life with CF. Continue reading CYSTIC FIBROSIS WIND SPRINT 66: CIRCUIT TRAINING 1

Newly Discovered CF Mutations Could Be Why Some People with CF are Living Longer

Researchers hypothesize that the newly-discovered mutations help re-hydrate the airways, discouraging bacterial build-up in the lungs.

Despite a narrow average lifespan, there is a big range in how severely cystic fibrosis (CF) affects the lungs and other organs depending on an individual’s specific genetic variation, and even in how long patients sharing the same, most common genetic mutation are able to survive with CF.

This led researchers at Boston Children’s Hospital to wonder if other genetic mutations could be protective against CF’s effects. Recent findings published in the American Journal of Respiratory Cell and Molecular Biology suggest that may be the case.

“There are some patients at one end of extreme severity who need a lung transplant very early in life, then others whose clinical presentation seems to stabilize so that they can live into the fifth and sixth decades of life,” says Pankaj Agrawal, MBBS, MMSc, principal investigator and medical director of The Manton Center’s Gene Discovery Core at Boston Children’s, who was the co-first author on the study.

To find out why, Agrawal and researchers at Boston Children’s — including Ruobing Wang, MD, a pulmonologist, and Craig Gerard, MD, PhD, chief of the Division of Respiratory Diseases — conducted the first-ever longitudinal analysis of genetic modifiers related to CF.

They combed through a population of nearly 600 CF patients registered at the Boston Children’s Cystic Fibrosis Center and found five individuals who stood out because of their advanced age — in their 50s or 60s — and relatively normal lung function.

“Given the large size of our center’s patient population, we were able to find a number of individuals at this rare ‘extreme,'” says Wang, who was co-first author on the paper.

A new hypothesis for mitigating cystic fibrosis

To discover the genetic variants, the researchers collected blood from these patients and performed whole exome sequencing on their DNA, analyzing the “coding” section of the genome that is responsible for most disease-related mutations.

Sequencing the genes of these five Boston Children’s patients — a cohort known as “long-term non-progressors” — the researchers found a set of rare and never-before-discovered genetic variants that might help explain their longevity and stable lung function.

The gene variants are related to so-called epithelial sodium channels (ENaCs), semi-permeable cellular pathways responsible for reabsorbing sodium in the kidney, colon, lung and sweat glands.

“Our hypothesis is that these ENaC mutations help to rehydrate the airways of CF patients, making it less likely for detrimental bacteria to take up residence in the lungs,” says Wang.

The discovery brings ENaCs into the limelight as a potential new therapeutic target.

“For example, if we could target ENaCs with a small molecule or an antibody-based drug, we might be able to incur a protective effect against CF’s progression,” says Agrawal, who is also a physician in the Boston Children’s Division of Newborn Medicine.

Based on their findings, the team is now doing further studies to analyze the genetics of patients at the other end of the CF spectrum — those with extremely severe clinical presentation of symptoms at a young age.

Story Source:

Boston Children’s Hospital. “Some people with cystic fibrosis might live longer because of genetic mutations: Researchers hypothesize that the newly-discovered mutations help re-hydrate the airways, discouraging bacterial build-up in the lungs.” ScienceDaily. ScienceDaily, 25 October 2017. <https://www.sciencedaily.com/releases/2017/10/171025150620.htm>.

Materials provided by Boston Children’s HospitalNote: Content may be edited for style and length.

We Can, Right? – Guest blog from USACFA Fall 2017 Scholarship Winner

By: Jacob Greene

Cystic Fibrosis is an awkward disease. Whether it’s coughing attacks in the middle of tests, the infamous CF digestive issues (for professionalism’s sake I will leave it at that, but you know what I mean), or loud treatments in the morning and at night, there are many awkward aspects to cystic fibrosis. CF’s median life expectancy is no different. Continue reading We Can, Right? – Guest blog from USACFA Fall 2017 Scholarship Winner

You are invited to attend a free web-cast event SATURDAY, APRIL 22, 2017

RARE LUNG DISEASES PATIENT EDUCATION DAY ON CYSTIC FIBROSIS, CHILDREN’S INTERSTITIAL LUNG DISEASE AND PRIMARY CILIARY DYSKINESIA

REGISTER NOW AT:
https://attendee.gotowebinar.com/register/6993341835513746691

This event is co-sponsored by the American Thoracic Society, the Cystic Fibrosis Foundation, the Children’s Interstitial Lung Disease Foundation and the Primary Continue reading You are invited to attend a free web-cast event SATURDAY, APRIL 22, 2017

OWN IT: Cystic Fibrosis Survival Rates in the United States vs. Canada

A study published in the Annals of Internal Medicine concluded that “the median age of survival [is] 10 years higher [for CF patients] in Canada than the United States.”

If you’re wrapped up in the world of cystic fibrosis news like I am then you’ve probably seen this study floating around the Internet for the Continue reading OWN IT: Cystic Fibrosis Survival Rates in the United States vs. Canada

‘Stunning’ gap: Canadians with cystic fibrosis outlive Americans by a decade

‘Stunning’ gap: Canadians with cystic fibrosis outlive Americans by a decade

Continue reading ‘Stunning’ gap: Canadians with cystic fibrosis outlive Americans by a decade

Making it Matter Ep. 25 – Salty Cysters

Lea Faraone, from the Salty Cysters, joins the podcast today to talk about her life with cystic fibrosis. At 26, she works as an oncology nurse, and is an advocate for people with cystic fibrosis. She uses the @SaltyCysters social media platform to spread educational awareness Continue reading Making it Matter Ep. 25 – Salty Cysters

Making it Matter Ep. 24 – Dealing with Disease Progression

Julia and I take a question from my most recent Facebook Live on the Boomer Esiason Foundation page, which asks about the progression of cystic fibrosis and how we deal with it.

Since cystic fibrosis is a progressive disease, it can take an emotional Continue reading Making it Matter Ep. 24 – Dealing with Disease Progression