THE ROLE OF IVACAFTOR
Running Head: THE ROLE OF IVACAFTOR
The Role of Ivacaftor in Improving the Quality of Life and Functioning of Patients
Diagnosed with Cystic Fibrosis
Audrieanna Raciti
State University of New York Institute of Technology
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The Role of Ivacaftor in Improving the Quality of Life and Functioning of Patients
Diagnosed with Cystic Fibrosis
Part I: Problem, Purpose, and Significance
Background
Cystic Fibrosis (CF) is a genetic disorder usually diagnosed in infancy or
childhood that predominately occurs in Caucasians, affecting approximately 70,000
people worldwide (Ramsey et al., 2011). It is the most common potentially lethal geneticlinked disease of whites in Europe, North America, New Zealand, and Australia, resulting
from a “failure of innate lung defense mechanisms as a result of airway dehydrations”
(Clunes & Boucher, 2008). CF has been identified as a progressive lung disease caused
by genetic mutations in the coding of the Cystic Fibrosis transmembrane conductase
regulator protein (CFTR), an ion channel that regulates sodium and water transport of
many organs, including the lungs (Accurso et al., 2010). This fatal genetic disease results
in a decreased number of CFTR channels or mutations at the cell surface, which impact
channel functioning negatively, making them less effective (Van Goor et al., 2009).
Corbyn (2012) mentions that mutations in the CFTR gene may also cause too
much salt and not enough water to pass into the cells, turning the body’s secretions,
which normally act as a lubricant, into an abnormally thick, sticky mucus, clogging the
lungs and digestive system and making it difficult to digest food and even breathe.
According to Yu et al. (2012), nearly 4-5% of patients with CF carry a CFTR mutation
preventing the channels from opening and closing properly, leading to minimal chloride
transport. This disruption makes patients more vulnerable to chest infections, which
eventually destroy their lung parenchyma (Corbyn, 2012). These defects in the CFTR
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channel protein have been noted to affect the transport of chloride and other ions across
the cell membrane, resulting in malnutrition and poor weight gain related to pancreatic
insufficiency, electrolyte imbalances, and male infertility due to the blockage of the vas
deferens (Sheridan, 2012). This disease has also been correlated with other common
diagnoses, such as diabetes, osteoporosis, and hepatitis (Sheridan, 2012).
Although the life expectancy of those diagnosed with CF has increased from the
age of twenty-five in 1989, to currently the age of thirty-seven, there is still much work
that needs to be done in improving the lives of these inconvenienced individuals
(Accurso et al., 2010). This increased lifespan has been improved through the treatment
of pancreatic insufficiency and malnutrition that had once been the main predictor of
deaths within these patients, but this ten year increase has led to a new problem to be
faced: respiratory insufficiency.
Patients diagnosed with CF currently face a great burden when considering their
lifespan and quality of life. Although the predicted survival rate has improved over the
last several decades, quality of life has not corresponded with this trend, indicating a need
for better treatment therapies. Current medical intervention only provides symptomatic
relief and not an actual cure to the problem. This has only led to an increase of constant
suffering for those receiving no source of relief from their lifelong burden of troublesome
treatments and economic expenditures. The creation of a new medication that actually
seeks to resolve the dysfunction occurring in this disease could serve to both improve
lifespan and patient quality of life.
Purpose of the Research
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A diagnosis of CF appears offer no source of hope or cure for people who are
born with this debilitating disease. A new medication known as Ivacaftor (VX-770) has
recently been created to treat the cause of CF at the cellular level, eliminating all signs
and symptoms that correlate with this diagnosis. I see the addition of this medication to
the market as great news to many who currently are suffering with this illness, not
expecting to live past the age of thirty-five. This disease was one that I was not too
familiar with, and learning about a possible source of relief for what was once believed to
be an inescapable fate of lost years and suffering proved to be a topic of great interest to
me. The purpose of this study is to both learn more about the process and findings that
correlate with this diagnosis of CF, as well as to propose a study to learn if this
medication is effective in treating the disease or the symptoms of CF.
Significance
The discovery of CF was first identified by Paul di Sant Agnese, MD from
Columbia University, who studied sweat electrolyte levels in forty-three patients with CF
in comparison to fifty patients without these symptoms (Kreindler, 2009). His findings
revealed that in these patients, levels of sodium, potassium, and chloride were
significantly elevated in comparison to controls (Kreindler, 2009). It was at this point that
CF was first deemed a “disease of altered ion transport” manifested by dehydration
leading to increased sodium loss from the sweat glands (Kreindler, 2009).
Research has shown greater than 1500 CF-causing mutations in the ions of
symptomatic patients, most extremely rare (Sheridan, 2012). The G551D mutation occurs
in nearly 4% of patients with this genetic disease, resulting in a production of proteins
destructive to the cell’s surface (Hussar & Eckel, 2012). Van Goor et al. (2011) mention
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that 90% of patients with CF carry the F508 del CFTR mutation, resulting in CFTR
defects in channel encoding, preventing it from reaching the cell surface where sodium
and water typically pass through. The goal of therapy is to hydrate the airways to thin
secretions, and/or inhibit absorption to stimulate mucociliary clearance, which will result
in the prevention of secondary lung infection, due to an inability to pass the thickened
secretions and bacteria, common among patients with CF (Clunes & Boucher, 2008).
Current intervention for patients diagnosed only treat the signs and symptoms that
are associated with CF such as steatorrhea, respiratory difficulties, and pancreatic
insufficiency that is caused by the thick production of clogging mucus as a result of a
poor regulation of salt and water within the tissues. Patients with CF are currently treated
symptomatically with antibiotics, mucolytics, and bronchodilators for lung infections,
anti-inflammatories to prevent damage to the lung parenchyma, pancreatic enzymes for
pancreatic insufficiency and malnutrition, and DNase and hypertonic saline to decrease
the viscosity of mucus (Van Goor et al., 2009). Gentamycin has also been shown to
suppress “nonsense” mutations, but not sufficiently enough to alter the CFTR gene
(Sheridan, 2012). Other options for treatment have also included lung transplant, physical
therapy, and nutritional services, with a medial survival age of only thirty-seven years
considering these interventions (Sheridan, 2012).
New medications being studied hope to decrease the burden associated with
current lifelong medications and treatments, by actually treating the disease at the cellular
level through repair of the defective CFTR protein, slowing lung damage and the multiple
symptoms presented with this disease (Accurso et al., 2010). A pharmaceutical company,
known as Vertex, has created a new medication that is promising for those dealing with
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the burden that current treatment offers, by actually repairing the CFTR, altering the
movement of salt and water across these channels in a way similar to those without this
defective gene (Accurso et al., 2010). This medication, referred to as VX-770, Kalydeco,
or Ivacaftor was approved in 2012 by the Federal Drug Administration (FDA) for
treatment of patients age six and older with the G551D mutation present in patients with
CF (Eckford, Li, Ramjeesingh, & Bear, 2012). Multiple pharmaceuticals have attempted
to mimic the effects of this medication on the CFTR gene malformation (flavonoids,
sulfonamides, phenylglycines, benzimidazolones), but at this point, have been
unsuccessful at achieving a comparable result in efficacy due to increased toxicity and
less than satisfactory study results (Sheridan, 2012).
Current interventions have placed a significant burden for those with this lifelong
genetic illness, including the knowledge that their lifespan and quality of life is
significantly diminished. This medication hopes to prove itself as a better alternative to
current medications that only temporarily fix the ailments of patients diagnosed with CF,
and proves to instead be a permanent cure. This new medication serves the purpose of
increasing the lifespan of individuals diagnosed with CF as well as improve functioning
and quality of life in a multitude of various ways.
Part II: Research Question, Hypothesis, and Definitions
Research Question
The research question that I plan to answer is: “What is the role that Ivacaftor
plays in improving the quality of life and functioning of patients diagnosed with CF”?
Hypothesis
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My hypothesis will be directional: I believe that the use of the Ivacaftor
medication, (which works directly at the cellular basis of the cause of CF) will improve
the functioning and quality of life of patients diagnosed with this illness in comparison to
placebo intervention, or other medications that previously only symptomatically provided
temporary relief of the disease.
Definitions
My research proposal will be a level II study as I will test the efficacy of VX-770
(Ivacaftor) on patients with a diagnosis of CF in relation to overall quality of life and
daily functioning. There are several variables that I will be assessing within my study,
both dependent and independent. The independent variables within my study (the parts of
measurement under control) are the administration of Ivacaftor in terms of dosage,
frequency, and time span, and the administration of placebo. The dependent variables, the
variables that change based on the manipulation of the independent variables, will be
respiratory functioning as measured by multiple instruments, sodium concentration,
weight gain, and quality of life identification as indicated by the Cystic Fibrosis
Questionnaire-Revised (CFQ-R).
Cystic Fibrosis Questionnaire, Revised (CFQ-R)-100 point questionnaire with higher
scores indicating decreased negative influence of CF on life functioning, and lower
scores indicating increased negative influence of CF on life functioning.
Cystic Fibrosis Transmembrane Regulator (CFTR)- Ion channel that regulates sodium
and water transport of many organs across the cell membrane.
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Placebo- A medication with no therapeutic benefit, made to resemble the pill being
studied exactly, without the participants being aware whether this is the medication being
studied or not. May also be called a “sugar pill”.
Quality of Life (QOL) Identification- General well being of an individual within society.
Respiratory Functioning- Measures of studies to determine how effective the lungs are
working, ability of gasses to pass easily and effectively through the lung tissue.
Part III: Theoretical Framework
There are two theories that I believe would be applicable to this research
proposal: these include Kolcaba’s “Comfort Theory” and Rozzano Locsin’s “Caring
Through Technological Competency” theory.
Kolcaba’s Comfort Theory
Within Kolcaba’s theory of comfort, she believes comfort exists in the phase of
three different forms: relief, ease, and transcendence (Kolcaba, 2010). Kolcaba describes
that comfort can also be maintained through the use of sociocultural, environmental,
spiritual, and physical self (Kolcaba, 2010). Patients are viewed within this model as
having health care needs that are identified by the patient or family in the practice setting
with comfort and relief from pain and suffering being the ultimate goal (Kolcaba, 2010).
Kolcaba identifies intervening variables as those in which the patient and providers have
little control over, such as the course of the illness, family support, and financial status
(2010). Health-seeking behavior (HSB) is seen as both the integrity of the institution (in
terms of values and financial situation of the organization) as well as best policies and
practice (protocols utilized within the health care system to collect new and supportive
evidence for the treatment of patients and illnesses).
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This theory is applicable as the treatment of CF though the use of this new
medication, Ivacaftor, serves the main purpose of ensuring comfort within these patients
long-term through effective relief, not merely by prolonging their illness with inadequate
symptomatic measures that have been previously utilized. Accurso et al. (2010) utilized
Kolcaba’s Comfort Theory as they mentioned that the purpose of their study was to
increase comfort and quality of life (QOL) among patients suffering from the debilitating
disease of CF. Their findings were discovered following answered items on a
questionnaire specifically for patients suffering from CF manifestations, known as the
CFQ-R, post treatment of Ivacaftor in comparison with participants taking placebo
(Accurso et al., 2010). Test results revealed that subjects taking Ivacaftor following the
period of forty-eight weeks showed in improvement in both comfort and diminished
negative influence of CF manifestations pertaining to quality of life when compared to
placebo (Accurso et al., 2010).
Ramsey et al. (2011) also applied the principles of Kolcaba’s comfort theory
within their study to identify the effectiveness and improvement of QOL through the use
of this medication in terms of respiratory status, nutritional status, and overall general
well being. It was also discovered through the use of the CFQ-R that administration of
Ivacaftor resulted in a overall improved state of health and satisfaction with life status
following a trial period of this medication in comparison to placebo (Ramsey et al.,
2010).
Locsin’s Technological Competency theory
When considering Razzano Locsin’s applicability to this proposal, I see this
creation of Ivacaftor as being highly relatable to his “Caring Through Technological
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Competency” theory. As the twenty-first century evolves and the use of new and
improved medications for the treatment of our patients are created, Locsin stresses that
the basic idea of caring within the nursing profession will continue to hold true and serve
as a representation of everything that we do (Locsin, 2005). The trend is now moving
more towards a biomedical era that is significantly different from the way in which
patients have been cared for in the past (Locsin, 2005). The main idea of nursing,
however, the art of caring, will remain unchanged, as caring continues to be the most
“essential and the most direct expression of nursing service” (Locsin, 2005).
Nurses are now faced with the challenge of providing the most personal care to
our patients while simultaneously treating holistically through complex forms of
healthcare technology. Advances in modern medicine have made the healthcare field
much more advanced than in previous years with the use of glucometer testing, computer
documentation, and electronic medication administration records, but to prevent the
depersonalization between nurses and their patients, we must keep this core aspect of
nursing within us (Locsin, 2005).
My research articles consider the creation of Ivacaftor for patients diagnosed with
CF as a new medication that proves to be more effective than any other medication that is
currently available to the public. The main purpose of this medication serves to improve
the functioning and quality of life among these individuals with this diagnosis, placing
the needs of the patient at the center of our role as caregivers. I feel this statement highly
relates to this theory that has been identified within Razzano’s theory of technology and
caring.
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Lubamba, Dhooghe, Noel, and Leal (2012) applied Locsin’s model to their
research through the administration of Ivacaftor to improve the malabsorption and
steatorrhea present in 85% of patients resulting in discomfort and a failure to thrive due
to significant weight loss. The researchers also believed the use of this pharmaceutical
would also resolve distress among the 97-98% of infertile males due to clogged or absent
vas deferens as a result of the decreased mucociliary clearance often problematic within
these patients (Lubamba et al., 2012).
The utilization of modern technology, as mentioned in Locsin’s theory, did not
prevent any depersonalization among the care of the patient and the healthcare workers,
as the main ideals of caring in nursing were carried out through the entire process.
Technology did not serve as an impediment in the care of these individuals, but more as
an advancement toward the improvement in QOL and functioning. Within this study, the
dehydration and mucosal thickening which compromised airway clearance, making CF
patients more prone to infection and resulting in “airway destruction, respiratory failure,
and death” was significantly reduced following administration of this newly
manufactured medication (Lubamba et al., 2012).
Sheridan (2012) also addressed the elements of Locsin’s model within her study
of this oral CFTR potentiator. The creation of Ivacaftor was shown to increase the gating
activity of an activated, though malfunctioning CFTR channel, allowing sodium to pass
through more easily (Sheridan, 2012). This relative improvement of 16-17% resulted in a
five year or more survival rate past expected rates, also impacting the rate of decline of
lung functioning and overall patient suffering (Sheridan, 2012). The administration of
this medication during the trial periods also indicated an ability of Ivacaftor to address
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nearly 4% of the 70,000 CF patients in the United States and Europe carrying the G551-D
mutation, seen most commonly within the Celtic populations (Sheridan, 2012).
Part IV: Literature Review
During my literature review, I summarized my findings into several different
topics. I believed it was important first to get a better understanding of the clinical
manifestations of CF, so I will discuss this first, followed by the pharmacokinetics of
Ivacaftor and how it effects patients with this disease. Finally, I will list the advantages of
Ivacaftor evidenced in research and how this medication has proved effective in multiple
areas of life functioning, including respiratory, sodium concentration and channel
transport, nutritional status, and the results of the CFQ-R as indicators of improved QOL.
Manifestations of the Disease
There are many clinical manifestations that coincide with a diagnosis of CF, with
lung disease the primary cause of death resulting from dehydration of airway surfaces
from increased sodium concentration (Van Goor et al., 2009). Lung disease has been
shown to gradually decline 1-2% each year with CF (Sheridan, 2012). Patients may also
have difficulty gaining weight as a result of ineffective absorption of nutrients by the
digestive system (Ramsey et al., 2011).
Song, Chiu, and Yoon (2012) mentioned that chronic sinopulmonary disease was
shown in affected patients demonstrating “persistent colonization” by multiple invading
organisms, gastrointestinal and nutritional abnormalities, salt depression, chronic
metabolic acidosis, and obstructive azospermia (an inability to secrete sperm) in males.
Hussar and Eckel (2012) identified chronic cough, persistent lung and sinus infections,
pancreatic insufficiency, and other complications such as diabetes in those with a
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diagnosis of CF. With ineffective mucociliary clearance, dehydration of the periciliary
gel layer (PCL) results in collapse of cilia within the bronchial tree, thickening of the
mucus as a result of being stationary, and the creation of mucus plugs and plaques
forming on airway surfaces (Clunes & Boucher, 2008). This occurrence often leads to
bacterial bronchiectasis, one of the most common causes of death following diagnosis
(Clunes & Boucher, 2008).
Pharmacokinetics of Ivacaftor
Ivacaftor has been noted as the first treatment for CF to treat the underlying cause
rather than just its symptoms, it has been categorized as a Pregnancy Level B medication,
as it is probably excreted in breast milk (Hussar & Eckel, 2012). This small blue pill is
currently on the market for around $294,000 yearly, prescribed twice daily (Corbyn,
2012). Research trials performed by Vertex Pharmaceuticals have approved this
medication for use among patients six years and older without hepatic or renal
impairment. (Corbyn, 2012).
Possible adverse effects include headache, abdominal pain, upper respiratory
infection (URI), nasal congestion, diarrhea, rash, nausea, and dizziness, with no serious
effects noted at this time (Song et al., 2012). Trial studies have also shown relatively
steady levels of plasma concentrations that were achieved by days three through five with
twice-daily administration, with a two to fourfold increase in drug potency when
administered simultaneously with lipid-dense foods such as eggs, peanut butter, cheese
pizza, and butter (Song et al., 2012). As a “potentiator”, this medication was originally an
investigational oral tablet designed to increase the time that activated channels remained
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open at the cell surface, allowing vital ions the opportunity to pass through (Ramsey et
al., 2011).
Compared with placebo, Ivacaftor resulted in a statistically significant
improvement in pulmonary function, CFTR activity, weight gain, and overall QOL for
both children and adults (Davies, Li, Yen, & Ahrens, 2011). Ataluren, another CFTR
potentiator still in clinical studies, hopes to cure a specific gene mutation present in 10%
of patients with CF, predominantly those of Jewish heritage (Corbyn, 2012).
QOL Indicator #1: Improved Respiratory Functioning
Accurso et al. (2010) identified that after fourteen days, participants taking VX770 showed respiratory improvements up 5.6 points in the 150mg group, 5.6 points in the
250mg group, and 2.8 points in the placebo group, with an average improvement of
around eight points following twenty eight days. Ivacaftor also resulted in improved
functioning of the CFTR channel with nasal cells and sweat glands, indicating a
measurable improvement in lung functioning (Accurso et al., 2010).
Forced expiratory volume (FEV) was improved by 10.6 points when the use of
Ivacaftor was compared with placebo, with effects seen as little as two weeks (Ramsey et
al., 2011). Patients on VX-770 were also 55% less likely to suffer from respiratory
distress, 67% were free from pulmonary exacerbations, and 40 fewer exacerbations were
experienced following forty-eight weeks when compared with placebo (Ramsey et al.,
2011). Ramsey et al. (2011) also discovered that 75% of the treated subjects had
increased FEV, ten fewer instances of hospitalizations over this time period when
compared with placebo, and that overall, pulmonary exacerbations, cough, hemoptysis,
and decreased pulmonary functioning occurred less frequently within the control group.
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In summary, Ivacaftor reduced the number of days hospitalized, exacerbations, and
intravenous antibiotics (IVAB) needed to treat CF, with increased FEV after two weeks
resulting in improved airway clearance (Ramsey et al., 2011).
A study performed by Sheridan (2012) found that after twenty-four weeks of
treatment, a 10.6% respiratory improvement from baseline occurred when compared with
placebo. Ivacaftor-related improvements were also shown to sustain after sixty years of
age, proving its beneficial effects in patients with severe, long-standing disease (McKone,
Li, Yen, & Davies, 2011). Song et al. (2012) also achieved a 55% reduction in the risk of
respiratory distress by week forty-eight following intervention with Ivacaftor.
Polenakovik and Sanville (2012) also determined that administration of VX-770
while hospitalized with CF steadily improved oxygen saturation and arterial blood gases.
Patients also appeared to require less time on BiPAP, eventually with supplemental
oxygen no longer indicated (Polenakovik & Sanville, 2012). Patients also refused to
pursue lung transplant due to respiratory improvements as a result of this medication’s
efficacy (Polenakovik & Sanville, 2012).
QOL Indicator #2: Sodium Concentration
In clinical trials, sweat chloride concentration after two weeks decreased 32.9
mmol/L with those receiving 25mg, 40.4mmol/L in those receiving 75mg, and
42.3mmol/L in those receiving 150mg of Ivacaftor therapy (Accurso et al., 2010). After
twenty eight weeks, patients also had 48.1mmol/L less of sodium when compared with
placebo, showing evidence of improved reduction in sweat chloride levels following
administration of VX-770 (Ramsey et al., 2011).
QOL Indicator #3: Weight Gain
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A common symptom of patients with CF is inability to thrive and weight loss due
to pancreatic insufficiency and malabsorption, with demanding caloric needs, anorexia,
and decreased absorptive ability by the gastrointestinal epithelia (Ramsey et al., 2011).
Ramsey and associates (2011) found that after forty-eight weeks with placebo and
antibiotics, patients gained 0.4kg, with a gain of 3.1kg under these same circumstance
with substitution of Ivacaftor.
Borowitz, Ramsey, Dong, Yen, and Elborn (2011) showed an improvement in
body mass index (BMI) above the 50th percentile after forty-eight weeks, while patients
on placebo fell below this percentile during this same time period. Improvement in
weight gain was also seen at week forty-eight following treatment with Ivacaftor
compared with placebo in a study performed by Davies et al. (2011). Song and colleagues
(2012) also noted a similar improvement in weight gain following forty-eight weeks, with
patients gaining 2.7kg more weight when compared with placebo.
QOL Indicator #4: Cystic Fibrosis Questionnaire- Revised
Each CFQ-R was scored on a 100-point scale, with increased scores indicating
decreased burden of CF symptoms on QOL, while lower scored represented greater
burden of symptoms affecting QOL (Accurso et al., 201). Ramsey et al. (2011) identified
that patients on Ivacaftor scored 8.6 points higher on the respiratory domain of the test,
indicating improved QOL in this area. Nearly all of the subjects treated with the
medication improved 5% or more on the scale overall, with scores significantly higher in
all domains of the questionnaire when compared with placebo (Ramsey et al., 2011).
Part V: Methodology
Design and Setting
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In all of the researched articles, all participants were included in a randomized,
double blind, placebo controlled phase II trial and also a parallel design. The purpose of
this type of study is an experimental process in which neither the participants nor the
researchers administering the substance are aware of whether or not the substance being
given is a placebo or the actual medication being researched. The main benefit of this
type of procedure is to eliminate as much experimenter bias as possible, since it is not
possible to determine which substance will effect the participant and how. A parallel
design compares two test groups, with the first test group including participants who
received the Ivacaftor medication, and the other group being those who were
administered the placebo.
In one study, two randomized, double blind, placebo- controlled studies included
participants aged six through eleven yeas with the G551D mutation and decreased FEV
(Davies et al., 2011). The majority of the articles were successful in using this design
method and setting to evaluate the effectiveness of Ivacaftor in CF patients of all ages
with the G551D mutation. All experiments were conducted in a controlled, clinical
setting to receive the most accurate testing and be able to monitor any changes in patient
condition and laboratory work with the advanced technology at hand.
Ethical Considerations/ Consent Forms
Prior to the participation within the experiment, all subjects were given a consent
form that described their roles and rights during the experimental process, as well as
possible risks and side effects that may occur following oral ingestion of the Ivacaftor
medication. Consent in some of the studies may also have been administered in some of
the participants orally. Patients were promised confidentially during the study, with no
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present patient identifying data to comply with HIPPA rules and regulations pertaining to
patient privacy. Subjects were also given the option to withdraw from the study at any
time.
Population/Sample Characteristics and Attributes
For purposes of this data collection, participants were typically greater than six
years of age with a diagnosis of CF, the G551D mutation on at least one CFTR, and a
FEV volume significantly lower than that expected for an average person of similar age,
gender, and weight (Van Goor, Yu, & Burton, 2011). In 2010, Accurso et al. performed
a study, which utilized CFTR ion-channel function, pulmonary function, and healthrelated QOL. Within this study, subjects were required to be eighteen and older with a
current diagnosis of CF, at least one CFTR gene, a FEV in one second, or 40% of more
of the predicted value for age sex, and weight (Accurso et al., 2010). The baseline
characteristics of the participants maintained relatively stable, without bias in regards to
selection of subjects based on sex body-mass index, financial status, or other
demographic data that may have potentially skewed the study results.
Sampling Procedures/Selection Assignment and Adequacy
Patients were considered for inclusion if diagnosed with CF and the defective
CFTR gene responsible for this characteristic respiratory insufficiency, weight loss, and
impairment in sodium transport that is evident within these individuals to ensure that no
insignificant outliers were introduced to skew the results. A nonrandom sample was best
indicated for this experimental study of CF patients, as we specifically pinpointed
specific characteristics that these individuals needed to be included for study. As
previously indicated, patients considered for inclusion must have been at least six years
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of age, with a diagnosis of CF, a defective G551D mutation on at least one CFTR, and a
diminished FEV. For these studies, factors such as marital status, demographics, or race
were all included into one group, as it was considered insignificant to separate
participants based off of these characteristics. This selection criteria allowed the collected
data to include only those persons whose results would reveal pertinent data for purposes
of the research findings and results.
Data Collection Methods and Tools
Data collection tools were used to measure signs of improved respiratory
function, FEV, pulmonary exacerbations over a set period of time, and days spent
hospitalized following both a diagnosis of CF and subsequent respiratory insufficiencies
necessitating medical attention. Usage of IV antibiotics for the treatment of pulmonary
infections was also compared over this trial period between Ivacaftor and placebo
intervention. To measure effectiveness of sodium concentration within the cells, sweat
chloride levels were measured periodically at set intervals compared with placebo.
Another indicator of improved overall quality of life among patients with a
diagnosis of CF is the ability to gain weight, since these patients often rapidly lose weight
due to malabsorption related to their pancreatic insufficiency and increased caloric needs.
This is caused by alteration in their gastrointestinal epithelia, limiting their ability to
absorb any nutrients and calories vital to sustain weight. Patient’s weight was measured
by frequent weigh-ins during the 48 weeks of therapy with Ivacaftor versus placebo.
Finally, to assess quality of life functioning as shown in the CFQ-R, patients were
assessed with a questionnaire worth 100 points, with improved scores showing
diminished signs and symptoms of debilitating effects following the diagnosis of CF.
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This scale assesses multiple indicators of functioning within life, such as ease of
mobility, respiratory functioning, and overall feeling of wellness (Van Goor et al, 2011).
Interval data collection and measurement appears to be more accurate, and was
the level of data that was most appropriate for the collection of data required for this
research. All of the measurable variables within my study (respiratory functioning,
sodium levels intracellulary, weight loss/gain, and the CFQ-R) were all compared based
on specific numerical figures and scales in comparison of Ivacaftor to placebo.
Reliability
Reliability within a study reflects the idea that the same tool used to reach a
conclusion will give us the same conclusion if repeated several times on the same object.
Following administration of Ivacaftor among subjects suffering from CF manifestations,
across all the research articles, all of the participants achieved a comparable relative
improvement among various domains of improved respiratory functioning. These studies
all indicated improved FEV, fewer hospitalizations and exacerbations, and improved
mucociliary clearance following a trial period of Ivacaftor administration.
Validity
Validity differs from reliability in that this is the assurance that the tool used to
measure the changing variable is accurate with what it is designed to measure. A tool
may be reliable, but not necessarily be valid in certain situations. The experiments within
the articles contained internal validity due to their ability to address the proposed
question, as well as external validity, as the results hold true among multiple populations,
which fall within the specified sample selection.
Stability
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Stability within research is the ability to resist change over multiple sources or
time. The articles referenced within this study all remained stable in their conclusion that
Ivacaftor was shown to improve QOL of patients with a diagnosis of CF based on
experiment results when compared with placebo and pre-treatment with the CFTR
potentiator. Findings from each study concluded that weight gain, improved respiratory
functioning, and improved functioning of the sodium channels resulting in decreased
mucus plugging were all indicators of an improved state of well-being among these
individuals.
Credibility
The research reviewed for this study ensured credibility due to their publication
into major well-acclaimed research journals. Credibility was also achieved as the authors
were all well-educated professionals in healthcare, and the studies all seemed to result in
the same conclusion, that Ivacaftor is a potential method of treatment effective in
improving the functioning of patients with a diagnosis of CF. There was potentially some
bias present within these studies as they required a nonrandom sample, although
numerical figures were accurate and conducted via a double-blind experiment.
Accuracy
The interval method of data collection helped to ensure the accuracy of the
findings within each study. Although personal behaviors and opinions are pertinent parts
of data collection in certain forms of research, such as qualitative research, the use of
numerical data is important for the quantitative research articles used for my study. The
tools used for data collection were precise measurement tools that have shown accuracy
in determining functioning of many vital organs of the body such as the lungs, kidneys,
THE ROLE OF IVACAFTOR
22
and digestive system. Methods of data collection measuring FEV, BMI, and sodium
concentration are all accurate tools for precise data collection needed for this research
study.
Plan for Analysis
Analysis planning had occurred from the very beginning of my research proposal,
to ensure that my thoughts and ideas stayed on track as I moved forward through the data
collection, synthesis of the literature, and study findings. I believe that at this time
adjustments need to be made towards the advancement of effective medications in the
treatment of patients suffering a significantly diminished quality of life due to CF.
Ivacaftor appears to be the only FDA-approved medication available to the public for
actually treating CF at the source of the disease cellularly, with its efficacy only targeting
those with the G551D gene on the defective CFTR mutation. This gene is only present on
4% of patients with CF, leaving 96% of those diagnosed still without adequate treatment
(Anonymous, 2012). Further research needs to be performed to span a greater percentage
of those still with no known permanent cure from exacerbation of symptoms.
I would not change my variable of interest for this study, as my chosen
independent and dependent variables were effective in determining which methods have
been most effective in QOL and daily functioning. The comparison of placebo and
Ivacaftor in its relation to the dependent variables (respiratory functioning, nutritional
status, sodium concentration, and CFQ-R were all effective measures to determine the
potential advantages of this medication on this targeted population.
The statistical techniques used were adequate in helping to achieve the most
informed and accurate results needed for obtaining my results. Findings may have been
THE ROLE OF IVACAFTOR
23
biased as this population sample was chosen based on certain defining characteristics, but
this was necessary to ensure the experimental population possessed the qualities that were
pertinent to answer the research question originally sought: To determine the role VX770 plays in improving the quality of life and functioning of patients diagnosed with CF.
Conclusion
I can only hope that future advances in research and technology can help to
improve the lives of those individuals suffering from a chronic mental or physical illness
in which there currently is no cure. Terminal illnesses such as CF, cancer, and
Alzheimer’s not only decrease the time allotted to spend with loved ones and of QOL in
many instances, but these illnesses have also resulted in many years of enduring
suffering. Research plays a key role in the field of healthcare more than many may
possibly know. The study of new and innovative ideas affects all of us at a personal,
local, and national level, and it is our role as professional healthcare providers to continue
these advancements for the purpose of benefitting our patients on all levels of care.
THE ROLE OF IVACAFTOR
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