Antenatal Bre-Lax Education for Perinatal Anxiety Reduction and Self-efficacy Among Pregnant Women in Karachi's Urban Slums

Introduction:Pakistan is ranked fifth among the most populous countries with a total population ofaround 260 million in spite of a 77 years long history of family planning programs in thecountry. The year 2015 was the culminating year of the Millennium Development Goals(MDGs) for Pakistan as well as in other countries, yet the indicators for achieving MDGs4 (reduce child mortality) and 5 (improve maternal health) have remained unfavorable.Moreover, the current sustainable development's goal (SDGs) has added additionalresponsibility on the country to improve indicators on population control in addition tothe FP2030 vision and commitments.Pregnancy is a significant milestone in a woman's life, bringing joy and expectation.However, it also comes with some challenges, as the body undergoes physical changes whileemotional and psychological changes arise within the women. Despite all these changes,pregnancy is a transformative journey that prepares women for motherhood, making it botha beautiful and demanding experience . However, with the passage of time, there is risingrecognition that pregnancy can also bring psychological challenges within the women.Women are increasingly seen as vulnerable towards the mental health issues like anxietyand depression. Acknowledging these challenges is crucial to providing the necessarysupport and care for pregnant women during this transformative period. It is seen thatDepression and Anxiety are considering as common mental health issues during pregnancy,but recent research suggests that anxiety may be even more prevalent than depression.Emerging evidence indicates that expectant mothers are more likely to experience anxiety,highlighting the need for support for maternal mental health.Pregnancy related anxiety is not only associated with the expected mother but also has agreat influence on the prenatal environment. According to the Fetal ProgrammingHypothesis, a developing fetus is highly sensitive to its environment, especially duringrapid growth stages. Factors like maternal anxiety can lead to physiological changes thataffect the fetus critically. If these influences occur during crucial developmentalstages, they may cause long‐lasting effects in the baby's physical health and as well asin metabolism. Essentially, the conditions in the womb shape long‐term health outcomes.This means that stress and other environmental factors during pregnancy don't just impactthe mother but they can have lifelong effects on the child's body and as well as on itsfunctions.Pregnancy‐related anxiety is strongly linked to various negative health outcomes for boththe mother and baby. Studies consistently shows that high levels of anxiety duringpregnancy can increase the risk of preterm birth, leading to possible complications forthe newborn baby. It is seen that women are more vulnerable toward mental healthdisorders like Anxiety and Depression during the time period of prenatal period, which isclosely associated with the health of the pregnant women and as well as the children.Children born to mothers who experience significant anxiety may face developmental delaysas they grow. Anxiety can also negatively impact the childbirth process, contributing toprolonged labor and increasing the need for pain relief or sedation during delivery.These highlight the crucial role of maternal mental health in pregnancy. When a motherexperiences high stress or anxiety, it can affect both the course of labor and the baby'searly development. Understanding and addressing pregnancy‐related anxiety is essential toimproving birth outcomes and promoting healthier development in children.There are many factors which are associated with the Anxiety among pregnant women, whichincludes socio‐economic factors, demographic factors and environmental factors. Adversechildhood experiences are one of the major factors associated with the Anxiety amongpregnant women. Childhood neglect, abusive or harsh parental behavior, and gender‐baseddiscrimination at an early age can have a profound psychological impact, leading tomental health disturbances such as anxiety and stress during pregnancy. Women who haveexperienced Adverse Childhood Experiences ACEs are more vulnerable to psychologicaldisorders, including anxiety, depression, and post‐traumatic stress during this criticalperiod. It has been seen that those women who faced adverse childhood experience are morevulnerable towards the psychological disorders like Anxiety, Depression and Traumaticstress during the pregnancy. Due to these mental health disturbance in the duration ofthe pregnancy, the risk of the tobacco consumption like cigarette and chewable tobaccoincreases in women and they start intaking such things for mental relaxation but itresults in increasing Anxiety and Psychological disorder and also has a bad impact onfetus. Poverty is one of the important factors which impacts the mental health ofpregnant women significantly. Financial struggles, such as unemployment, householdresponsibilities, housing issues, and rising food expenses, create constant stress to thehuman mind. The increasing cost of daily necessities adds to their burden, making itdifficult to manage basic needs while preparing for a child. These challenges heightenanxiety among the pregnant women, who is conscious about providing a stable environmentand the basic life needs to their baby. The pressure of balancing financial insecuritywith physical and emotional well‐being can be overwhelming and play a vital part inincreasing the risk of high psychological issues during pregnancy.Low income can negatively impact the nutrition and care of an unborn baby which can be areason for increasing Anxiety among pregnant women. Expecting mothers may strugglefinancially, facing challenges in affording medical care and maintaining their child'swell‐being. The cost of prenatal checkups, proper nutrition, and future child‐rearingexpenses can add significant stress and Anxiety . Early marriages play a vital role inpsychological disorder like Anxiety and depression among pregnancy. Adolescent motherswhose age between 11 to 19 years often experience significant anxiety as they navigatepregnancy, childbirth, and parenting in very early time period of their life . Theoverwhelming responsibility can lead to fear of unpreparedness, regret, shame, andemotional distress among them. Many struggles with depression, guilt, loneliness, andsocial isolation, while also facing strained relationships. The mental exhaustion fromthese challenges can deeply impact their well‐being, making motherhood a stressful andanxiety‐inducing experience at a young age .Domestic violence is recognized as one of the biggest sources of the psychologicaldisturbance in the time period of pregnancy. The World Health Organization (WHO) declareddomestic violence as violent and a gender‐based behavior which causes emotional,physical, sexual, and psychological damage to the women . Pregnancy itself has a greatimpact on the physical and psychological health of women, when it emerged with the otherfactor like violence it results in the adverse impact on the women's health which effectsthe health of the mother and the child as well . Domestic violence during pregnancy is aserious issue that significantly affects a woman's quality of life especially affectingwomen's mental health. Research on this topic is increasing worldwide, highlighting itsimpact on both developed and developing countries. Experiencing violence while pregnantposes severe risks to both the mother and fetus, leading to heightened anxiety, emotionaldistress, and physical harm. The fear, stress, and trauma associated with domesticviolence can severely impact maternal mental health, making it a critical public healthconcern .Pregnant women living in urban slums face unique challenges that differ significantlyfrom those in more resource‐rich settings. Limited access to healthcare, poor livingconditions, financial insecurity, and low literacy levels all contribute to heightenedstress and anxiety during pregnancy. Unlike populations where structured antenataleducation, psychosocial support, and relaxation interventions are commonly available,women in slum communities often lack such opportunities. This absence of supportiveinterventions leaves them vulnerable to unmanaged anxiety, negative perceptions ofchildbirth, and poor maternal outcomes .Social support is widely recognized as a buffer against pregnancy‐related stress andanxiety. In slum populations, many women lack robust support from spouses, families, andpeers. This absence of emotional and practical assistance heightens their risk ofisolation and depression and erodes their confidence in navigating pregnancy andchildbirth. Interventions such as structured antenatal education and breathing orrelaxation techniques, shown to be effective in other groups, remain largely untested inthese marginalized communities. This study aims to assess whether structured breathingand relaxation techniques with antenatal education can reduce perinatal anxiety andenhance childbirth experiences in slum populations, where such strategies have not yetbeen adopted. This research will provide evidence on the value of low‐cost, culturallyadapted interventions in underserved communities, supporting better maternal mentalhealth and promoting safer, more positive birth outcomes.Aim of the Study The aim of this study is to evaluate the effectiveness of the BreLaxbreathing and relaxation technique and structured antenatal education, individually andin combination, in reducing perinatal anxiety and enhancing childbirth experiences amongpregnant women living in the slums of Karachi.Objectives of the Study Primary Objective Objective To determine whether the combinedintervention of BreLax and structured antenatal education produces a greater reduction inperinatal anxietyHypothesis: ‐ H₀₁ (Null): The combined intervention does not significantly reduce perinatalanxiety compared to routine antenatal care. ‐ H₁₁ (Alternative): The combined intervention significantly reduces perinatal anxietycompared to routine antenatal care Secondary Objectives Objective 1 To assess theindependent effect of structured antenatal education on perinatal anxiety levelscompared to routine care.Hypothesis: ‐ H₀1: Structured antenatal education has no significant effect on perinatal anxietycompared to routine care. ‐ H₁1: Structured antenatal education significantly reduces perinatal anxiety comparedto routine care..Objective 2 To evaluate the independent effect of the BreLax technique on perinatalanxiety levels compared to routine care.Hypothesis: ‐ H₀2: The BreLax technique has no significant effect on perinatal anxiety compared toroutine care. ‐ H₁2: The BreLax technique significantly reduces perinatal anxiety compared toroutine care.Objective 3 To compare the relative effectiveness of the combined intervention versuseach individual intervention in reducing anxiety scores.Hypothesis: ‐ H₀3: There is no significant difference in anxiety reduction between the combinedintervention and the individual interventions. ‐ H₁3: The combined intervention results in a significantly greater reduction inanxiety compared to the individual interventions.Objective 4 To examine differences in childbirth experiences across all study groups,using the QACE, to identify whether interventions contribute to more positive maternalperceptions of birthHypothesis: ‐ H₀4: There is no significant difference in childbirth experiences among the fourstudy groups. ‐ H₁4: There is a significant difference in childbirth experiences among the fourstudy groups.Study MethodologyStudy Design:This study will be conducted as a population‐based Prospective Randomized Open, BlindedEnd‐point (PROBE) design with three parallel arms. The control group will receive routineantenatal care, which includes general advice and information on pregnancy but excludesstructured education or formal training in breathing and relaxation techniques. The oneintervention group will receive routine antenatal care along with guided sessions in theBreLax breathing and relaxation technique. However, the intervention group will receive acombination of both structured antenatal education and BreLax sessions in addition toroutine care.Eligible participants will be randomly assigned to one of the four study arms using acomputer‐generated randomization sequence with allocation concealment through sealedopaque envelopes. Double blinding will be ensured by keeping both biostatistician andoutcome assessors unaware of group allocation; participants will not be informed of thespecific intervention type beyond routine care, and outcome assessors, includingbiostatisticians, will remain blinded during data analysis.Data will be collected at multiple time points: baseline before the intervention (T0),immediately after completion of the intervention sessions (T1), and in the late thirdtrimester or early postpartum period (T2). Childbirth experience data will also becaptured using the Questionnaire Adverse Childhood Experienc (QACE) within two to fourweeks after delivery (T3). This repeated‐measures design allows for evaluation of bothshort‐term and longer‐term effects of the interventions on maternal anxiety andchildbirth experiences, while maintaining methodological rigor through randomization andblinding.Study Site:The study will be conducted at the primary health care based antenatal care units locatedat slums of Karachi Pakistan, of KarachiParticipants and Eligibility Criteria:Pregnant women aged between 18 and 40 years, with a gestational age of 12 to 28 weeks atrecruitment, residing in selected slum areas of Karachi, and willing to participate byproviding informed consent will be eligible for inclusion. Participants must screenpositive for mild to moderate anxiety using a validated tool such as Pregnancy‐RelatedAnxiety Questionnaire‐Revised 2 (PRAQ‐2), and women with a history of intrauterine deathor stillbirths will be considered. Women will be excluded if they have a diagnosedpsychiatric illness requiring medical treatment, high‐risk pregnancy complications suchas pre‐eclampsia or severe anemia, or if they are already practicing structuredrelaxation techniques or psychological interventions. Those unable to communicate in Urduor the local language, women with recurrent pregnancy loss, those already onantipsychotic or anti‐anxiety medications, and women who screen positive on the Fear ofBirth Scale will also be excluded from participation. This approach ensures that thestudy focuses on women most likely to benefit from the intervention while safeguardingthose for whom participation may pose additional risks.Study Arms / Intervention Groups Arm 1: Control Group ‐ Receive routine antenatal care and advice during ANC visits Arm 2: BreLaxIntervention Group ‐ Routine antenatal care ‐ BreLax Exercise sessions during four ANC visits ‐ Includes: ‐ Deep breathing techniques ("breath in‐breath out") ‐ Progressive muscle relaxation ‐ Guided relaxation practice ‐ Each session approximately 15‐20 minutes Arm 3: Combined Intervention Group ‐ Routine antenatal care ‐ Structured educational guidance by a midwife ‐ BreLax exercise during ANC visits ‐ Combination delivered over four visits, Each session approximately 15‐20 minutesIntervention Duration ‐ Total duration: 8‐12 weeks ‐ Four structured sessions aligned with routine ANC visits Table 1: SPIRIT schedulefor enrollment, allocation, and post‐allocation. TIMEPOINT Study Period Enrolment,Baseline & before the intervention immediately after completion of the interventionsessions (T1) late third trimester or early postpartum period (T2) two to four weeksafter delivery T0 T1 T2 T3ENROLMENT:Eligibility screen X Informed consent X Allocation XINTERVENTIONS:Combined Group (BreLax + Antenatal Ed) X X X X Individual Group A (BreLax Only) X X X XControl Group (Routine Antenatal Care) X X X XASSESSMENTS:Sociodemographic & Contextual Factors XPrimary Outcome:Perinatal Anxiety (PRAQ‐R2) X XSecondary Outcomes:Childbirth Experience (QACE) X XData Collection Procedure 1. Baseline assessment: ‐ Demographic data ‐ Obstetric history ‐ Baseline anxiety score 2. Follow‐up assessments: ‐ After completion of intervention (post 4 visits) ‐ Possibly at third trimester or pre‐delivery 3. Data will be collected using structured questionnaires administered by trained datacollectors Blinding ‐ Participants and trainer cannot be blinded due to behavioral intervention ‐ Outcome assessors and Biostatistician will be blinded to group allocation to reduce biasSample Size:The study will be conducted as a PROBE randomized controlled trial with three parallelarms. The minimum clinically relevant difference in perinatal anxiety scores to bedetected between the intervention and control groups is set at approximately 5 points,based on prior literature. The estimated standard deviation for perinatal anxiety scoresis expected to 8 points from baseline. The significance level (α) is fixed at 0.05 fortwo‐tailed testing, and the statistical power (1 ‐ β) is set at 0.80, ensuring an 80%probability of detecting a true effect if present. Participants will be allocated equallyacross the four arms, following a 1:1:1 ratio.Based on these assumptions, the total sample size required for the study is approximately200 participants . This number will be distributed evenly across the four arms, resultingin about 68 participants with 20% attrition rate, final 85 per arm and 255 in total. Thisallocation is expected to provide sufficient statistical power to detect meaningfuldifferences in perinatal anxiety reduction and childbirth experiences between the controlarm and the three intervention arms.Randomization:Participants in this study will be randomly allocated into one of the four study arms toensure comparability and reduce selection bias. The study biostatistician, using blockrandomization to maintain equal group sizes, will prepare a computer‐generatedrandomization list in advance. Allocation concealment will be achieved through sealed,opaque envelopes that will only be opened at the time of enrollment. This process ensuresthat neither the participants nor the enrolling staff can predict group assignment.Randomization will be stratified by gestational age (10‐16 weeks and 17‐24 weeks) tobalance potential differences in baseline anxiety levels across groups. By employing thismethod, the study will maintain methodological rigor and enhance the validity ofcomparisons between the control, educational intervention, BreLax intervention, andcombined intervention groups.Intervention:The complex intervention developed by Leutenegger V et al. (2024) and is grounded inBandura's self‐efficacy theory shown in figure:1. As per Bandura 25, self‐efficacy refersto an individual's belief in their ability to perform a specific behavior in a givencontext. It consists of two key components: outcome expectation and self‐efficacyexpectation. Outcome expectation relates to an individual's anticipation of the potentialconsequences of a behavior, if a person believes a particular action will produce adesired result, they are more likely to engage in it. Self‐efficacy is shaped andachieved by four primary sources: personal performance, observational learning (vicariousexperience), verbal encouragement, and physiological or emotional states 24As a structured breathing and relaxation program integrated into antenatal education,with the goal of reducing perinatal anxiety and enhancing maternal confidence duringpregnancy and childbirth. It combines supervised practice, culturally adapted educationalmaterials, and home‐based reinforcement to ensure both short‐term and sustained benefitsfor women living in the slums of Karachi.Self‐Efficacy Theory The intervention is grounded in Bandura's self‐efficacy theory,which emphasizes that an individual's belief in their ability to perform a specificbehavior strongly influences whether they engage in it. Self‐efficacy consists of twocomponents: outcome expectation (belief that a behavior will lead to a desired result)and self‐efficacy expectation (belief in one's own ability to perform the behavior). Foursources shape self‐efficacy: personal performance, vicarious experience, verbalencouragement, and regulation of emotional/physiological states.COM‐B Model for Behavior Change The intervention also incorporates the COM‐B model, whichidentifies capability, opportunity, and motivation as essential components for behaviorchange. ‐ Capability: Women will develop psychological and physical capability by learningcorrect breathing patterns, relaxation postures, and understanding the rationalebehind the techniques. Educational materials will be adapted to their literacylevels, and healthcare providers will guide them systematically. ‐ Opportunity: Social and physical opportunities will be created through livedemonstrations, corrections by trained midwives, and provision of pictorialinfographics with clear instructions. The supportive environment of antenatalsessions will encourage adoption of the techniques. ‐ Motivation: Reflective motivation will be fostered by highlighting the benefits ofBreLax for reducing anxiety and improving birth experiences, while automaticmotivation will be reinforced through repeated practice until the techniques becomehabitual.In the BreLax program, women will gain confidence by successfully practicing breathingand relaxation techniques, observing peers performing the same exercises, receivingsupportive feedback from midwives, and experiencing reduced stress and emotional arousal.Visual infographics in Urdu, combined with practical demonstrations, will reinforce theseskills and empower women to continue practicing at home. Figures 1 and 2 illustrate theconceptual framework and infographic‐based reinforcement of self‐efficacy in maternalhealth outcomes.Figure:1 Conceptual framework of the BreLax intervention impact on maternal health outcomFigure 2 also represented the self‐efficacy theory through pictorial info graph. The infograph represents that through picture and guidance in urdu language, mother becomeself‐efficacious towards the change and by empowering them through guidance in form ofpractical as well as educational pamphlet, pregnant mother will feel relax and stressfree during their pregnancy.Women are likely to effectively execute breathing and relaxation methods and see thatother women can do these techniques as well. They will also obtain supportive remarksfrom qualified personnel and midwives. Utilizing the visual infographic or practicalinstructions on breathing and relaxation techniques provided by experienced personnel,women will be encouraged to persist in their practice at home. Participants will getguidance through the exercises from experienced personnel or via graphical infographics,and they will be encouraged to continue practicing at each visit.COM‐B Model for Behavior Change among Women Using BreLax Exercise Technique Theintervention was developed to empower and develop self‐efficacy of the pregnant women atslums. In order to achieve desire outcomes, COM‐B model will be used for behavior changeamong participants. There are three important components of COM‐B model: i. capability,ii. Opportunity, iii. Motivation. The model is preciously design and shown in figure:2.In the model, woman participants develop their Capability through Physically &Psychologically for their behavior change which includes the real understanding towardsthe intervention and acquired correct posture and movement appropriately. Additionally,intervention must be designed to ensure clarity of message with their level of literacyand also healthcare provider will guide them before handing over it. Additionally,opportunities encompass both physical and social supports for pregnant women, such aslive demonstrations with feedback, pictorial infographics with clear explanationsprovided in advance, encouragement from designated healthcare staff, trained midwives forthis intervention, and in‐person training sessions. These resources and opportunitiesfoster both reflective and automatic motivation, empowering women to recognize thebenefits of adopting this technique and to integrate it habitually into their dailyroutinesFigure:3 COM‐B Model for Behavior Change among pregnant women, lead to reduction inperinatal anxiety.Intervention Delivery BreLax sessions will be delivered during routine antenatal visits,lasting approximately 30‐45 minutes. Women will be taught deep breathing techniquesemphasizing prolonged exhalation, progressive muscle relaxation, and guided relaxation invarious positions (standing, sitting, four‐foot, and lateral). Each participant willreceive Urdu‐language manuals and infographic materials, along with access to short audioor video instructions to support independent practice at home two to three times perweek.Midwives and healthcare staff will undergo structured training workshops to ensurefidelity in delivering the intervention. They will provide verbal encouragement, correctposture and breathing during sessions, and motivate women to continue practice outsidethe clinic. The intervention is designed to become habitual, enabling women to recall andapply the techniques during labour and stressful situations.Data Collection Tool:There are three parts of data collection tool, which are as follows 1. Socio‐demographic Scale (Age, Weeks of Pregnancy, ethnic status, Education level,Parity status) 2. The Pregnancy‐Related Anxiety Questionnaire‐Revised 2 (PRAQ‐R2) will be used toassess perinatal anxiety. This instrument consists of 10 items grouped into threesubscales: fear of giving birth (3 items), worries about bearing a handicapped child(4 items), and concern about appearance (3 items). Each item is rated on a 5‐pointLikert scale ranging from 1 ("definitely not true") to 5 ("definitely true"),allowing for straightforward responses and quantifiable measurement of anxietylevels across different domains. 3. The Questionnaire for Assessing Childbirth Experience (QACE) will be used toevaluate women's perceptions of their childbirth experience. This self‐reportinstrument is available in French, includes a validated English translation, and hasbeen used in both research and clinical practice. For this study, the 13‐item shortversion will be used, covering four subscales that measure different dimensions ofthe childbirth experience. Responses will be recorded on a 4‐point Likert scale, andresults will be dichotomized into "totally" versus "in part, not so much, not atall," with scores allocated accordingly. Higher scores indicate a more negativebirth experience, while a score below 19 reflects a positive childbirth experience.Supplementary Figure 3 depicts the study flow, enrollment to allocation and then analysisin the study.Outcome Measures:The primary outcome of the trial is self‐efficacy. Further relevant maternal and neonataloutcomes is summarized in Table 1, including the time points at which the measures willbe taken. Trained data collectors at each time point will administer all questionnaire toparticipants.Table‐1: Outcomes measures and time points Variables Measures Time points Primary OutcomePerinatal Anxiety & Self‐efficacy Pregnancy‐Related Anxiety Questionnaire (PRAQ‐R2):Evaluates pregnancy‐specific anxieties and fear of childbirth. T0, T3Secondary Outcomes Childbirth Experience Childbirth Experience Questionnaire QACE:Quantifies the 13‐item short version will be used, covering four subscales that measuredifferent dimensions of the childbirth experience. Responses will be recorded on a4‐point Likert scale. T1, T3 Sociodemographic & Contextual Baseline Profile: Age,nationality/ethnicity, living arrangements within the Karachi slum settings, educationalattainment, employment status, monthly family income, baseline gestational age, parity,prior obstetric history, medical history, and pre‐existing birth preparation. T0Statistical Analysis:The data will be analyzed using Stata version 17. Descriptive statistics will be used tosummarize baseline characteristics, with categorical variables presented as frequenciesand percentages, and continuous variables reported as means and standard deviations.Normality of the outcome variable (scores) will be assessed using the Shapiro‐Wilk testseparately for pre‐ and post‐intervention measurements in both the intervention andcontrol groups, as well as for the combined pre‐ and post‐intervention scores. Thecontinuous variable results between the control and intervention groups will be evaluatedusing paired sample t‐tests and will be used to assess mean differences between thecontrol and intervention groups from baseline.A repeated measures ANOVA will be conducted to evaluate the effect of group (interventionvs. control), time (pre‐ and post‐intervention), and their interaction on the outcomescores. The analysis will include 160 participants with measurements at multiple timepoints. Group will be considered a between‐subject factor, and time will be awithin‐subject factor. Partial eta‐squared values will be calculated to assess themagnitude of the effects. The model fit will be assessed using R‐squared and adjustedR‐squared values. The between‐subjects error term accounted for by the variable"id/group" will have 160 levels, with pooled covariance over groups. The assumption ofsphericity will be checked using the Huynh‐Feldt correction, and no further correctionwill be necessary (epsilon = 1.0000). Post hoc pairwise comparisons will be performedusing the Bonferroni correction to control for multiple comparisons, ensuring that thereported p‐values account for the increased likelihood of Type I errors.Data Management and Data Monitoring Data collection will be carried out by the principalinvestigator and trained research assistants using structured questionnaires. All datawill be entered directly into a secure, password‐protected electronic database designedspecifically for research studies. Each participant will be assigned a unique trialidentification number, and no personally identifiable information will be stored withinthe database. Data entry will include built‐in validation checks to identify invalidtrial numbers, out‐of‐range values, or mismatched follow‐up identifiers, which will beexcluded to maintain data integrity. Access to the database will be restricted toauthorized members of the research team, with permissions assigned by the investigator toensure confidentiality and security.Given the short timeframe of the study and the minimal risks anticipated forparticipants, a formal data monitoring committee will not be established. Instead, theresearch team will oversee ongoing monitoring of data quality, completeness, andparticipant safety throughout the study. Any unexpected adverse events or ethicalconcerns will be promptly reported to the Institutional Review Board, and the need for aformal monitoring committee will be reassessed if circumstances change. This approachensures that data are managed responsibly and monitored continuously while maintainingefficiency and ethical compliance.