- Identify study design and type of data in the study below

-Accurately summarize how the data analysis was done

-Logically critique the statistical data analysis conducted to evaluate the primary outcome of the study.

Introduction

Patients diagnosed with cancerin South Korea from 2006 to 2010 had a 5-year relative survival rate of 64.1%.¹Because the survival rate of patients with cancer has been on the rise, concerns regarding the mental health of these patients and their quality of life have also increased. Patients with cancer have a high level of psychological distress, and 20%-40% of this population is codiagnosed with depression and anxiety requiring therapeutic intervention.^2-4

Psychological distress has a detrimental effect on patients' overall state of health, self-management capabilities, length of hospitalization, and, ultimately, survival rate.^3,5,6In particular, patients with cancer who undergo radiation therapy exhibit significantly higher levels of psychological distress, especially indices of depression, such as negative feelings, compared with the general Korean population.^7,8One consequence of this is that patients' self-esteem is lowered, which is followed by an unwillingness to undergo treatment.⁹For these reasons, the development of therapeutic interventions that may mitigate such psychological distress are necessary to improve the self-esteem of patients with cancer undergoing treatment.⁹Typical radiation therapy requires patients to visit the hospital on weekdays for approximately 2-8 weeks.^10-12This overlap allows for both body and mind to be addressed together, providing for more holistic treatment. Recently, several studies have applied laughter therapy (LT) as a complementary intervention.^13-18To date, researchers have established that LT reduces a patient's level of depression, anxiety, and stress; relieves physical pain; increases self-esteem and quality of life; and enhances the immune system.^19-23

Among the many studies of LT in clinical settings, only one appears to have illustrated the mood state effects of LT in patients with breast cancer in South Korea.^13-16No study has yet evaluated changes in mood and self-esteem after LT among patients with cancer in South Korea. The current study aimed to investigate the effect of LT on the mood and self-esteem of patients with cancer undergoing radiation therapy in order to establish a theoretical basis for its use during cancer treatment.

Methods

This was a randomized, controlled, experimental study.

Participants and ethical approval

The institutional review board at Asan Medical Center in Seoul, South Korea, approved this study (approval number: 2012-0736). The study was conducted at the radio-oncology outpatient clinic at the Asan Medical Center. The inclusion criteria for participants were the following: 20 years of age or older undergoing radiation therapy while receiving LT, scoring between 0 and 1 on The Eastern Cooperative Oncology Group scale,²⁴and possessing the ability to comprehend and answer the questionnaire. The following patients were excluded: those who were currently diagnosed with recurrent or metastatic cancer and those who had been exposed to other LTs before this study. And the patients who were diagnosed with psychiatric problems, including major depressive disorder and anxiety disorder, and were taking antipsychotic medication were also excluded, because it could affect the outcomes of this study (mood state and self-esteem). Patients who met the inclusion criteria were enrolled into the study after providing informed consent. They voluntarily agreed to participate; declared an understanding of the study purpose, methods, and potential adverse effects; and were informed of their right to withdraw at any time without penalty. They also received a leaflet with information on LT.

Intervention

All intervention sessions were facilitated to by a staff nurse in the emergency department. Only one nurse administered the experimental therapy in order to maintain the facilitating quality. She received LT certification upon completion of a 34-hour LT course at the Korea Laughter Clinic Academy. The LT intervention details were adapted to accommodate the LT program already being conducted at the time at the Asan Medical Center, which is open to all patients with cancer and their family members on a regular basis. However, the LT program in the Asan Medical Center was closed during the study period to avoid exposing the wait list control group to additional LT that was not study protocol directed.

Participants in the experimental group received 60-minute LT sessions once per day over 3 consecutive days, with each participant receiving a total of three treatment sessions. Sessions began with a 10-minute introduction on the effect of laughter followed by 40 minutes of patient participation in physical activities directed to make them laugh aloud. These activities included laughing aloud for 15 seconds, moving the upper body from side to side to the beat of music, and clapping hands and stomping feet while smiling and saying "I love you" to the person beside them. The program ended with an opportunity for all participants to share their feelings, followed by meditation with quiet music.

Participants in the wait list control group were provided with LT identical to that provided to the experimental group once they had completed the study.

Data collection, sample size and randomization, and statistical methods

Demographic data and disease characteristics for all participants was obtained from their medical records. The level of mood state and self-esteem of both groups were each measured twice: 1 week before the application of LT and immediately after completion of the third LT session.

The Korean version of the Profile of Mood States-Brief (POMS-B) was used to evaluate changes in mood states.^25,26The POMS-B consists of 30 questions, each using a 5-point Likert response scale.²⁶In addition to scoring total mood disturbance (TMD), the scale includes six subcategories: tension, depression, anger, vigor, fatigue, and confusion.²⁶Higher scores in each subcategory signify stronger mood states in the corresponding fields, whereas higher scores for TMD signify worsened mood states.²⁶

To measure self-esteem, the Rosenberg Self-Esteem Scale, developed by Rosenberg²⁷and adapted by Jeon,²⁸was used. It contains a total of 10 questions, 5 of which correspond to positive self-esteem and 5 to negative self-esteem. Responses to all items are rated on a 4-point Likert scale.²⁷Higher scores signify higher degrees of self-esteem and vice versa.²⁷

The required sample size was calculated according to a procedure in a previous study that applied a psychological intervention on patients.²⁹The mean TMD scores for the experimental and wait list control groups were 17.7 and ?1.7, respectively, with a standard deviation estimated to be 24.²⁹A sample size of 31 patients per group was necessary to compare the mean TMD scores between the groups, given a dropout rate of 20%, with a two-sided independentt-test, using a 5% significance level and a power of 80% (G*Power, version 3.1.1; Heinrich-Heine-Universitt Dsseldorf, Dsseldorf, Germany).

On a first-come, first-served basis, study participants were randomly assigned according to standard randomization procedures to the active LT experimental group or wait list control group by an investigator who had no clinical involvement in the study trials. Random numbers were stratified by sex, mixed in a 46 block, and generated online (http://www.randomization.com).³⁰Experimental group and wait list control group participants were distributed with a 1:1 ratio. Whereas participants allocated to the groups and data analysts were blinded to study assignment, the nurse who facilitated the LT program and the researchers were aware of the allocated group.

Following the primary intention-to-treat (ITT) analysis, a secondary per-protocol (PP) analysis was conducted. Missing values were replaced by the last observation carried forward. The mean difference between the pretreatment and post-treatment values was measured in the two groups and analyzed with a Mann-Whitney test and independentt-test. General and disease characteristics were examined by the chi-square and Fisher exact test using SPSS software, version 18.0 (IBM, Armonk, NY).

Results

A total of 436 patients were receiving radiation therapy between November 2012 and February 2013; 219 who did not meet the eligibility criteria were excluded. Two hundred and seventeen patients were invited to participate and received information about this study. Of these, 153 declined to participate because they were busy, were not interested in this subject, could not meet the schedule, or felt fatigued. Sixty-four patients agreed to participate in the study; 33 were randomly allocated to the experimental group and 31 to the wait list control group. Before the collection of baseline data, two patients dropped out of the study. Therefore, 62 participants were included in the ITT analysis. PP analysis was performed on 22 active LT experimental group members who participated in LT at least once and who completed the pre- and post-questionnaires.

Eleven members from the experimental group were excluded from the PP analysis. While 2 members did participate in LT, their post-therapy results were not measured because the therapy was completed at the time of the post-questionnaire and they resided in the regional provinces. Although the remaining 9 members answered the pre- and post-questionnaires, they were excluded because they did not participate in LT. Two could not participate because of schedule conflicts with their radiation treatments, 2 because of weak physical strength, and 1 because of concurrent illness with a cold. Moreover, 4 stated they did not participate because they felt the program was cumbersome. In the control group, 27 were included in the PP analysis and 1 was excluded because of exposure to LT before the post-questionnaire. Another was excluded because of missing follow-up (Fig. 1). The mean participation rate was 1.7 sessions for the ITT analysis and 2.5 sessions for the PP analysis.

Assessed for Eligibility (n=436) Excluded (n=372) - not meeting inclusion criteria (n=219) - Declined to participate (n=153) Randomized (n=64) Allocated to Experiment Group (n=33) Allocated to Control Group (n=33) Analyzed for intervention to treat (n=33) Analyzed for intervention to treat (n=31) Excluded from analysis (n=0) Excluded from analysis (n=2) - refused to participate (n=2) Analyzed for per Pr01000' 01:22) Analyzed for per protocol (n=29) Excluded from analysis (F11) Excluded from analysis (n=2) ' not participated in laughter therapy (n=9) - exposure to laughter therapy (n=1) - flu loss (n=2) - flu loss (n=1)