Living Well: Protocol for a web-based program to improve quality of life in rural and urban ovarian cancer survivors

May combine two claims.

Ovarian cancer survivors often have long-term symptoms such as anxiety, depression, sleep problems, fatigue, physical symptoms, reduced health-related quality of life, and a poor outlook.

“Ovarian cancer (OC) survivors commonly experience chronic symptoms including anxiety, depression, sleep disturbances, fatigue, physical symptoms, poor health-related quality of life (HRQOL), and a generally poor prognosis.”

• Also stated in: § Introduction · plain

  “Ovarian cancer (OC) survivors commonly experience chronic and often debilitating symptoms including anxiety, depression, sleep disturbances, fatigue, physical symptoms/side effects, existential concerns, poor health-related quality of life (HRQOL), and a generally poor prognosis [1–9].”

• cites [1] sourceNot checked — no full text of the source
• cites [2] sourceNot checked — no full text of the source
• cites [3] sourcePartly supported

  The Discussion reports that sleep disturbance commonly persisted through the first year after ovarian cancer diagnosis and was associated with diminished quality of life; the Introduction also describes anxiety as common and notes poor prognosis. The paper links depression to poor sleep, but does not establish that ovarian cancer survivors commonly have chronic fatigue or the unspecified physical symptoms in the claim. Its follow-up extends only to one year, so it does not establish longer-term persistence of the full symptom list. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [4] sourceNot checked — no full text of the source
• cites [5] sourcePartly supported

  The Patient Characteristics section (page not available in our copy) reports sleep disturbances and low energy at one year, as well as elevated anxiety, depression, and poorer physical and overall quality of life at study entry. But the study includes several gynecologic cancers, not ovarian cancer survivors alone, and reports that mood and quality of life improved over the first year. Its poorer-prognosis description applies to the regionally advanced group, not to ovarian cancer survivors generally. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [6] sourceNot checked — no full text of the source
• cites [7] sourceNot checked — no full text of the source
• cites [8] sourceNot checked — no full text of the source
• cites [9] sourcePartly supported

  The Results (page unavailable) report anxiety, insomnia, fatigue, pain and other physical symptoms as quality-of-life concerns among the ovarian cancer survivors studied. They do not establish that these symptoms are chronic or that depression is a common symptom; depression appears only as a possible pre-existing diagnosis in Materials and Methods. The introduction describes prognoses as ranging widely, rather than survivors having a generally poor prognosis. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Social isolation, stress, and depression are linked to biological processes that drive tumor progression and lower survival.

“Additionally, factors such as social isolation, stress, and depression are associated with key biological processes promoting tumor progression and poorer survival.”

• Also stated in: § Introduction · plain

  “Additionally, factors such as social isolation, stress, and depression are associated with key biological processes promoting tumor progression and poorer survival [10–15].”

• cites [10] sourceNot checked — no full text of the source
• cites [11] sourcePartly supported

  The Results and Discussion (page unavailable in our copy) link lower social support, greater distress, and depressed mood with impaired natural killer cell activity in ovarian tumors. The paper does not establish that these factors promote tumor progression or reduce survival in these patients; it says longitudinal research is needed to understand disease implications. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [12] sourcePartly supported

  The Results and Discussion (page not provided) link depression and stress to elevated macrophage MMP-9, and lower social support to tumor-cell MMP-9 and VEGF—factors the paper describes as supporting angiogenesis and invasion. The Conclusion says these mechanisms could have implications for survival, but the study does not establish an association with poorer survival. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [13] sourceNot checked — no full text of the source
• cites [14] sourcePartly supported

  The Introduction (page unavailable) links low social support and depressive symptoms to tumor biomarkers, while the Discussion describes stress-response pathways that may promote tumor growth. The study also associates lower social attachment with poorer survival, but its survival analysis found that neither past nor current major depression significantly predicted survival; it does not establish that the proposed biological pathways mediated survival. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [15] sourceSupported

May combine two claims.

Gene expression from dried blood spot samples was 85% concordant with venous PAXgene whole blood and peripheral blood mononuclear cell gold standards across 19,679 named gene transcripts, demonstrating robust and reliable technology.

“from dried blood spot samples were 85% concordant with gold-standards of venous PAXgene whole blood samples and peripheral blood mononuclear cells across 19,679 named gene transcripts, thus demonstrating that this is a robust and reliable technology [29].”

• cites [29] sourcePartly supported

  The Results section (“Individual gene-level correspondence”; page unavailable) reports correlations of r = .85 between dried-blood-spot expression values and each comparator across 19,679 named transcripts. That supports strong correspondence, but a correlation of .85 is not a measurement of 85% concordance. The Discussion also notes greater variability in some dried-blood-spot analyses, qualifying the broad claim that the technology is reliable. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Among cancer patients in DBS self-collection feasibility studies, 90-95% returned samples and 76-89% preferred DBS or had no preference versus venipuncture.

“In feasibility studies of DBS self-collection in cancer patients, 90–95% of participants returned DBS samples, and 76–89% reported either preferring DBS or having no preference compared to venipuncture [30, 31].”

• cites [30] sourceNot checked — no full text of the source
• cites [31] sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The conserved transcriptional response to adversity (CTRA) is a 53-gene composite linked to chronic stress.

“It will examine expression of the conserved transcriptional response to adversity (CTRA), a 53-gene composite associated with chronic stress, as well as involvement of lymphocyte subsets [24].”

• cites [24] sourcePartly supported

  The Introduction links the CTRA pattern to chronic stress. The Measurement section says the 53-gene contrast is one way to measure CTRA, not the definition of CTRA itself, so calling CTRA a 53-gene composite overstates the source. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

The Mindful Living intervention was found to be feasible and acceptable in single-arm trials.

“The intervention was feasible and acceptable, and preliminary data indicate increased HRQOL and decreased perceived stress and depression among OC survivors in single-arm trials [23].”

• cites [23] sourcePartly supported

  The Discussion (Principal Findings; page unavailable) reports high acceptability and moderate feasibility in a one-armed field trial. However, the Introduction names the intervention Living WELL, not Mindful Living, and the paper reports one field trial rather than multiple single-arm trials. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Early data from single-arm trials suggest that Mindful Living raised health-related quality of life and lowered perceived stress and depression in ovarian cancer survivors.

“The intervention was feasible and acceptable, and preliminary data indicate increased HRQOL and decreased perceived stress and depression among OC survivors in single-arm trials [23].”

• cites [23] sourcePartly supported

  The Results (Preliminary Outcomes; page unavailable) report improved ovarian cancer-specific quality of life and reduced perceived stress, plus a nonsignificant decrease in depressive symptoms. The Discussion (Principal Findings; page unavailable) describes these as preliminary findings from a one-armed field trial. The paper calls the intervention Living WELL, not Mindful Living, and reports one trial rather than multiple trials. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

Dried blood spot technology is feasible for field-based gene expression studies, and using DBS yields more representative samples than clinic-based designs.

“DBS technology has been shown to be feasible in field-based studies of gene expression and use of DBS supports more representative samples than are possible with clinic-based research designs [29].”

• cites [29] sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

No facilitator leads groups in both the Mindful Living and Healthy Lifestyles arms.

“The facilitators for Mindful Living do not lead any Healthy Lifestyles groups nor do Healthy Lifestyles facilitators lead Mindful Living groups.”

May combine two claims.

Mindful Living could substantially improve health-related quality of life and reduce distress in ovarian cancer survivors.

“The Mindful Living intervention has the potential to substantially enhance HRQOL and decrease distress in OC survivors.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Within each stratum, cluster randomization uses permuted blocks of size 2 or 4.

“The cluster-randomization for each strata employs permuted blocks of block size 2 or 4.”

May combine two claims.

Limiting enrollment to those with no more than one prior recurrence makes the sample more homogeneous, but it reduces generalizability and excludes people later in their disease course who could still benefit.

“This design has the additional advantage of providing greater study population homogeneity, but it also decreases study generalizability and limits access for individuals later in their disease trajectory who might still benefit from the intervention.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Facilitators learning their group's assignment one to two weeks before the group begins does not bias recruitment because the group slots are already full.

“Facilitators’ knowledge of group assignment the week before the group starts does not bias participant recruitment because the slots have already been filled for that group.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

When data are missing at random, a likelihood-based linear mixed model can handle incomplete observations and yield valid estimates.

“In the presence of missing data, under the assumption of missing at random (MAR), linear mixed model analysis which can handle incompletely observed participants and uses a likelihood estimation method will provide correct likelihoods and lead to valid estimates.”

• AssumptionThe authors state this as an assumption: Missing data are assumed to be missing at random.

Probably not a substantial claim: may not pass S3 (load-bearing).

Participants are assigned to intervention arms through cluster randomization stratified by time slot.

“Assignment to the intervention arms is done by cluster-randomization stratified by time slot.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Any variable showing a significant between-group difference will be included as a covariate when comparing outcomes across arms.

“Variables found to differ significantly between groups will be used as covariates in the comparison of outcome measures between treatment groups.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Each arm's groups are led by facilitators who received training specific to that intervention.

“Groups are led by facilitators trained specifically for their intervention group.”

Classified as probably not a substantial claim. May combine two claims.

The statistician generates randomization lists before enrollment, and allocation stays concealed until a group must be assigned.

“Randomization lists are generated by the statistician prior to participant enrollment and allocation remains concealed until a group needs to be assigned.”

May combine two claims.

The intervention could overcome earlier barriers to psychosocial intervention delivery and improve health-related quality of life in an understudied cancer group with high recurrence risk.

“The intervention has the potential to overcome prior barriers to the implementation of such psychosocial interventions and improve HRQOL in an understudied cancer population with a high likelihood of recurrence.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The group format also gives survivors a way to connect socially with other people who have ovarian cancer.

“The group-based approach also provides survivors with much-needed social connections to other individuals with OC.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Participants referred through non-clinic routes provide physician contact information during consent to verify self-reported clinical information.

“Participants who come through non-clinic referrals provide contact information for their physician as part of the consent process to verify self-report clinical information.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The study received IRB approval from the University of Iowa Holden Comprehensive Cancer Center (201911073), with reliance agreements from dedicated clinical sites.

“The study was approved by the University of Iowa Holden Comprehensive Cancer Center Institutional Review Board (201911073) with reliance agreements from dedicated clinical sites.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The trial is registered with ClinicalTrials.gov (NCT04533763).

“The trial is registered with ClinicalTrials.gov (NCT04533763).”

Classified as probably not a substantial claim.

All randomized participants will be included in an intent-to-treat analysis using every available data point.

“Intent-to-Treat (ITT) analysis will be performed using all available data for all randomized participants.”

May combine two claims.

Because the program is delivered online, ovarian cancer survivors can access it even where face-to-face psychosocial support is lacking, and rural populations can reach it easily, which helps address rural disparities.

“The intervention’s web-based platform is available to OC survivors in locations where in-person psychosocial support is not available and easily accessed by rural populations, thus addressing the issue of rural health disparities.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Intervention fidelity will be assessed by having two trained raters review and rate 20% of recorded sessions in every cohort within each arm.

“To assess intervention fidelity, 20% of recorded sessions in each cohort of each intervention arm will be reviewed and rated for fidelity by two trained raters.”

Probably not a substantial claim: may not pass S3 (load-bearing).

For multi-item inventories, coefficient alpha and test-retest correlations across the data-collection period will be assessed.

“The internal consistency (coefficient alpha) and test-retest correlations over the course of data collection will be evaluated for multi-item inventories.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Use of psychotherapy, psychotropic drugs, and services such as support groups is monitored at every assessment and controlled for when needed.

“We monitor for use of psychotherapy, psychotropic medications, and service utilization (e.g., support groups) at each assessment point and control for these if necessary.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Only the Research Coordinator can access the randomization sequence file.

“Only the Research Coordinator has access to the randomization sequence file.”