Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06294379 |
| Other study ID # |
OUH_SDM |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2022 |
| Est. completion date |
December 30, 2024 |
Study information
| Verified date |
February 2024 |
| Source |
Odense University Hospital |
| Contact |
Lærke K Tolstrup, PhD |
| Phone |
40295129 |
| Email |
laerke.tolstrup[@]rsyd.dk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This study aims to develop test and evaluate a Patient Decision Aid called "The Decision
Helper" among melanoma patients eligible for adjuvant treatment.
- Is the Decision Helper an acceptable tool for patients and clinicians and is it feasible
in clinical practice?
- Are there any differences in the levels of decisional regret in the patients who have
not used the Decision Helper (pre-implementation) compared to the ones who have
(post-implementation?
Description:
Malignant Melanoma Worldwide, the incidence of melanoma of the skin continues to increase.
Cutaneous melanoma is the most lethal skin cancer worldwide. In alignment with the global
trend, the number of Danes who are diagnosed with malignant melanoma has also increased
significantly during the last 50 years. In Denmark, approximately 400 persons are diagnosed
with metastatic disease each year. Although more people are diagnosed with melanoma, there
has only been a minor increase in the number of people who die from the disease. This is
primarily due to improved treatment modalities. The development of immunotherapy and targeted
therapy have been the most important breakthroughs in melanoma treatment. In the last decade,
immune checkpoint inhibitors (CPIs) have improved survival significantly for patients with
metastatic melanoma. However, the immune-related adverse events (irAEs) that patients may
experience can be severe and potentially life-threatening.
Adjuvant therapy When it comes to the treatment of malignant melanoma, it is not only in the
metastatic setting that treatment options have improved disease control. The scene has also
changed when it comes to adjuvant treatment where CPIs also play an increasingly important
role. Until recently, the standard of care after completely resected stage III melanoma was
active surveillance. In stage III melanoma the cancer has spread from the skin cells to the
lymph nodes, which means that these patients are considered to have a high risk of
recurrence; a part of them will at some point experience a relapse with metastatic disease.
Consequently, several drugs to prevent recurrence after surgery have been tested in melanoma
over the years, but until recently none had proven effective. The first drug to change this
was the CPI, Ipilimumab. In 951 patients with resected melanoma at high risk of recurrence
stage (IIIa, IIIb, or IIIc disease), the effectiveness of Ipilimumab as adjuvant therapy was
tested. The recurrence-free survival was significantly improved in favor of the patients who
had received Ipilimumab compared with placebo. 5-year rate of recurrence-free survival was
41% in the ipilimumab group, as compared with 30% in the placebo group. However, more than
half of the patients experienced severe irAEs. Ipilimumab was never approved as a standard
adjuvant treatment in Denmark due to the high risk of severe irAEs. However, in December 2018
two other CPIs, Nivolumab and Pembrolizumab, were approved as adjuvant treatment (for stage
IIIa, IIIb, or IIIc resected disease). Nivolumab has proved to increase recurrence-free
survival when compared to ipilimumab. 4-year recurrence-free survival was 52% in the
Nivolumab group and 41% in the ipilimumab group. In addition, only around 14% of the patients
who receive monotherapy with Nivolumab experience a grade 3 or 4 adverse events (AE). Similar
results were found in another study investigating the CPI, anti-PD1 antibody, Pembrolizumab.
The overall risk of recurrence was reduced by approximately 40% across stages as a result of
adjuvant therapy with Pembrolizumab after 3 years [12]. Despite the gain in recurrence-free
survival, there I not always a best/right decision regarding adjuvant treatment. In the
following the pros and cons for starting adjuvant treatment will be described in more detail,
illustrating the inherent dilemma between clinical benefit and irAEs.
The challenges of adjuvant therapy - to treat or not to treat There is prognostic
heterogeneity within the group of stage III melanoma patients. The risk of experiencing a
relapse varies depending on whether a patient is diagnosed with stage IIIA disease or stage
IIIC disease (AJCC 7th Edition). Thus, some patients have a low risk of recurrence, (stage
IIIA), while others are at greater risk (stage IIIC) following complete resection.
Patients with stage IIIC also have more to gain from a prognostic perspective than patients
with stage IIIA disease if they receive adjuvant treatment. Even though all patients with
stage III disease are eligible for adjuvant therapy, the decision to initiate treatment is
not unproblematic. Furthermore, the number of melanoma patients who are candidates for
adjuvant treatment is likely to increase in the future. Randomized controlled trials are
currently investigating if patients with stage IIB/C melanoma can also benefit from adjuvant
therapy. The argument is that these patients have a prognosis similar to patients with stage
IIIB melanoma.
In addition to the fact that some patients are considered to be at low risk of relapse, there
is also the question of toxicity. Almost 80% of the patients who receive adjuvant
immunotherapy experience some kind of irAE, and approximately 14% of the patients experience
severe irAEs that in some cases can be fatal.
Moreover, severe toxicities can impact patients´ quality of life. O´Reilly et al conclude in
a paper published in 2019 that melanoma patients who had received immunotherapy have
potentially experienced significant irAEs during treatment resulting in chronic conditions
and exposure to significant doses of steroids. Accordingly, they had significantly lower
health-related quality of life scores about physical, social, and physical role functioning
and general health compared with healthy controls. Moreover, if/when patients relapse with
metastatic disease, they are often offered treatment with the same drug as they would have
received in the adjuvant setting, which may support the argument that some of the patients
are better off waiting. On the other hand, patients of course prefer not to have a relapse.
Thus, there is not always an obvious best treatment and the decision to treat or not to treat
can be challenging. It is currently not well understood how patients eligible for adjuvant
immunotherapy make their decision to accept or not accept treatment, and careful
consideration and discussion about the potential risks and benefits must be carried out with
each patient. In addition to disease recurrence, physicians must keep several factors in mind
such as patient age, comorbidity, and personal preferences.
Patient involvement As it is impossible to predict which patients will benefit from the
treatment, international guidelines developed for other patient populations suggest that
adjuvant systemic treatment, particularly in cases where there is little to gain (for example
patients with stage IIIA disease), should be discussed with the patient. This recommendation
to include the patients when it comes to decisions about treatment and care is in line with
the general trend within the health care system. The Danish National Survey of Patient
Experiences (LUP) stresses that the dimension "patient involvement" is the most poorly rated
area of all dimensions rated by the patients in the survey. Moreover, the Region of Southern
Denmark decided in 2019 that Shared Decision Making (SDM) should be deployed in all hospitals
in the region. Thus both politicians as well as patient organizations have an increased focus
on involving the patients more engagement.
Shared Decision Making - a possible game changer According to the Danish Melanoma Group,
approximately 100 patients are eligible for adjuvant treatment annually at the Department of
Oncology, Odense University Hospital. Patients and physicians face the difficulties described
above, when having to decide which melanoma patients are to receive adjuvant therapy.
Sometimes the choice may seem obvious because the patients may have a relatively high risk of
recurrence. In other situations where the patients have a low risk of recurrence or
comorbidities which may make treatment with immunotherapy risky, it is more complex. In such
cases, SDM could be useful to support this preference-sensitive decision. SDM is defined as
"an approach where clinicians and patients share the best available evidence when faced with
the task of making decisions, and where patients are supported to consider options, to
achieve informed preferences and in making treatment decisions that align with these
preferences". A Danish lung cancer study from 2019 showed that patients who had been engaged
in SDM had lower decisional conflict and regret. Furthermore, they felt more confident about
the decision and the process facilitated that patients´ values played a more central role in
decision-making. One way to increase the level of patient-perceived involvement and make the
consultations in the outpatient clinic more uniform may be to use a patient decision aid
(PtDA) to support shared decision-making. If the patients experience that they are part of
the decision process, it may also result in a lower level of decisional regret as described
above.
Patient Decision Aids In other countries such as the United States decision-support tools
have been developed, containing information on what the patients need to know about stage III
melanoma. The patients can find information about the disease, substages, adjuvant therapy vs
active surveillance, side effects, and outcomes. With this information in mind, the patients
may be able to weigh the options with their treating oncologist to come to the right
decision. Only a few decision aids have been developed and tested scientifically in a Danish
context. As mentioned, adjuvant therapy as standard treatment is a relatively new treatment
option for patients with melanoma, and no recipe guides/describes how to reach the right
shared decision for the individual patient. However, a study carried out in oncology care and
pulmonary medicine demonstrates how the use of a patient decision aid (PtDA) enhanced SDM in
two different settings and helped increase focus on patient preferences [25]. This study used
a generic patient decision aid template, called "Decision Helper" developed by the Center for
Shared Decision Making in the Region of Southern Denmark (CFFB). Therefore, the center now
offers a platform for decision-aid templates that adhere to the certification and quality
criteria set by the International Patient Decision Aid Standards (IPDAS). Utilizing log-in,
healthcare providers have access to the platform and the template for building patient
decision aids (BESLUTNINGSHJÆLPER™) and will be able to build and develop PtDAs tailored to
their specific needs. The template is developed based on the IPDAS criteria.
Study 1 - Development of the Patient Decision Aid
Methods: As both patients and clinicians are the end-users of the PtDA, both groups will
participate in an iterative process to ensure that patient needs are prioritized and that the
PtDA is relevant, accurate, and easy to use. Thus, instead of just seeing the patients as a
source of data, they will play an active role in the design phase of the PtDA. A qualitative
approach will be applied using semi-structured interviews, as recommended in IPDAS
guidelines, where melanoma patients and clinicians will identify the type and amount of
information needed for creating relevant and appropriate PtDA. As a supplement to this,
another qualitative method (observational) will be used as a researcher (the project manager)
will observe the patient-clinician communication (before the introduction of the PtDA) in a
natural situation to collect data on the communication between the patient and clinician, how
the talk is organized and the level of patient involvement.
Phase 1: Preparation of the Patient Decision Aid
- Observation by researcher in the outpatient clinic - 5 consultations
- An expert group consisting of physicians and nurses will look at PROs and CONs for
receiving treatment/not receiving treatment
- Interviews with melanoma patients, who have already decided whether to receive treatment
or not, about their views and preferences and what they see as advantages and
disadvantages. An interview guide will be prepared to ensure uniformity and all aspects
are covered. Three patients who have accepted treatment and three patients who have
declined will be included.
Phase 2: Design of the Patient Decision Aid
The PtDA will be prepared following the views and preferences of patients and clinicians with
the following content:
- Introduction: It must be clear to the patients that a PtDA is used in the consultation
for the patient and the clinician to make a decision together
- The choices must be clear to the patient (observation or treatment)
- Focus on patient preferences - what matters to the patient
- Description of the different choices using 4 cards describing:
- PROs and CONs/risks and benefits
- Patient stories (patients who have made the choice already, see phase 1)
- Statistics (risk of relapse)
- Timeline (Description of the trajectory for both choices (treatment or
observation).
Data entered into IT platform 1. Draft prepared Information/data from phase 2 is entered into
the IT platform BESLUTNINGSHJÆLPER and the first draft is ready. The Center of Shared
Decision-Making will provide support and feedback.
User test - 2. draft prepared A user test is carried out, including individual interviews
with 3-4 patients and 3-4 clinicians. For the patients, a semi-structured interview guide
will be used that is based on the items from the Preparation for Decision-Making Scale.
Similarly, a guide will be prepared for clinicians. Based on the findings from the interviews
and usability testing, the decision helper will be refined, and changes will be entered into
the IT platform.
Trial period - 3. draft prepared The final version is printed and a trial period of
approximately 12 weeks will take place. If no further adjustments are required, the PtDA is
ready for implementation.
Study 2 - Evaluation of the PtDA Hypothesis: The implementation of the PtDA will result in an
increased level of patient involvement among melanoma patients eligible for adjuvant
immunotherapy. In addition, the patients will experience less decisional regret. Moreover,
the consultations in the outpatient clinic will become more uniform and consistent.
Aims: To investigate 1)the level of patient involvement and 2)decisional regret among
melanoma patients receiving adjuvant therapy before and after implementation of the PtDA. In
addition, 3) to examine if the consultations become more uniform and consistent.
Methods: Since the aim was to examine the level of patient involvement, decisional regret,
and the uniformity and consistency of consultations before and after the implementation of
the PtDA, it has been decided to use a pre-post study design. Although this design does not
take other factors that may change during the study into account, it may be able to suggest
if the outcome is impacted by the intervention. A mixed method approach will be used to
evaluate the effect of the PtDA, using both quantitative data and the Decision Regret Scale)
and qualitative data (individual interviews and focus group interviews.) A convergent design
is selected, in which survey data and interview data are collected in parallel over the same
period. This will be described in more detail for each of the three aims in the following.
- Level of patient involvement Qualitative data: The level of patient involvement will be
examined using a qualitative approach, by conducting interviews with eligible patients before
and after implementation. Due to the exploratory nature of the study, the sample size cannot
be determined in advance, but the aim is to include 10-15 patients for both pre and
post-interviews depending on when data saturation has been reached. A purposive sample of
patients will be selected to ensure maximal variation in gender, age, and treatment choice. A
semi-structured interview guide will be designed to make the interaction as smooth as
possible and the interviews will carried out by the same interviewer to ensure uniformity.
Members of the project group will participate in the coding and analysis of the interviews.
Braun and Clarke six step theory will be used for analysis.
Quantitative data:
Qualitative data: Focus group interviews will be carried out with clinicians who take part in
outpatient consultations before and after implementation to elucidate if the consultations
have become more uniform and consistent after the inclusion of the PtDA. Due to the limited
number of physicians and nurses caring for/treating the patient population, it will only be
possible to carry out two focus group interviews before and after. The interviews will
consist of approximately 5-6 clinicians each. As with the individual interviews, an interview
guide will be prepared and the interviews conducted in a semi-structured manner. The same
content analysis approach will be applied to the group interview as described above.
Quantitative data: The plan is to measure the time spent on the individual consultation to
elucidate if the time consumption differs between the two groups i.e. if the length of the
consultations has been more uniform after implementation.
- Decision regret Quantitative data: Patients who have not been exposed to SDM
(pre-implementation) and patients who have been exposed (post-implementation) will be asked
to complete the Decision Regret Scale (DRS). The DRS is a questionnaire that measures
distress and remorse after a healthcare decision. The scale consists of 5 questions. The
scores are converted into a 0-100 scale following the user manual. A score of 0 means no
regret; a score of 100 means high regret.
Statistics:
Primary outcome: DRS (0-100 scale, 20 steps), mean before/after compared by linear regression
with bootstrapped standard errors (To take into account non-normality of scores). Secondary
analysis: Tested with Wilcoxon rank-sum test Secondary outcomes: DRS above cutoffs for mild
(5-25), respectively, moderate/strong regrets (≥ 30): Compared by logistic regression.
Supplementary analysis: In supplementary analyses above regressions will be adjusted for
patient characteristics, which might have changed between the before and after periods.
Sample size calculations:
Collaborators The study is supported by the head of department at the Department of Oncology
at Odense University Hospital. Two patient representatives and the team (physicians and
nurses) that is responsible for the treatment will play a vital part in developing the PtDA
to ensure that all aspects are covered. Furthermore, the study will be carried out in
collaboration with "The Center for Shared Decision-Making". Finally, a cross-sectional
survey, including various questionnaires, was sent out to 427 melanoma patients across
Denmark in March this year. The Decision Regret Scale (DRS) is one of the questionnaires in
the survey and accordingly, it will be elucidated if the patients who have received adjuvant
treatment in 2019 and 2020 have had any decisional regret. The results will be helpful as
historical background data for our project.
Perspectives The studies will be based at the Department of Oncology, OUH, but the project is
highly relevant for all melanoma patients in Denmark. It is expected to change how outpatient
consultations take place, enabling the patients to participate in important decision-making
regarding their treatment and care. It is currently not well understood how patients eligible
for adjuvant immunotherapy make their decision to accept or not accept treatment. It is
expected that the PtDA for melanoma patients receiving immunotherapy in the adjuvant setting
can be used nationwide and serve as an example for other researchers/clinicians who wish to
design a similar tool for other patient populations receiving immunotherapy. Moreover,
because the researchers also aim to evaluate the tool by comparing the level of patient
involvement before and after implementation of the "Decision Helper", it will be elucidated
if the designed tool makes a difference.
