Search Plan & Results
| Question: | Does regular use of marijuana have long-term effects on mental health? |
| Date of Literature Review | March 2019 |
| Inclusion/Exclusion Criteria: | Age: Adults aged 18 and over Health status: no pre-existing mental health conditions or co-morbid conditions that increase vulnerability to mental health conditionsNutrition-related problem/condition: marijuana, but specifically edibles (edible ingestion of marijuana)Study design preference: case control study design, randomized controlled trials were allowed; longitudinal studies were excluded (did not meet age criteria or frequency of marijuana usage criteria)Date of Publication: 1995-2019Language: English only |
| Electronic Databases: | Google Scholar; PubMed |
| Search terms: | marijuana edibles AND mental health; marijuana ingestion; marijuana AND mental health; marijuana AND psychiatric effects |
| Summary of articles identified to be reviewed | Total number of hits: 221 Total number of articles considered: 11 Number of Included Primary Research Articles: 6 Number of Included Peer Reviewed Articles: 1 Total Number of Included Articles: 7 Number of Articles Considered but Excluded: 4 |
| Inclusion List: | 1. Buckner, Ecker, and Cohen. “Mental Health Problems and Interest in Marijuana Treatment among Marijuana-using College Students.” Addictive Behaviors 35.9 (2010): 826-33. Web. 2. Andrea H. Weinberger, Lauren R. Pacek, Christine E. Sheffer, Alan J. Budney, Joun Lee, Renee D. Goodwin, Serious psychological distress and daily cannabis use, 2008 to 2016: Potential implications for mental health?, Drug and Alcohol Dependence, Volume 197, 2019, Pages 134-140. 3. “Self-medicating with Marijuana May Offer Pain Relief but Carries Possible Mental Health Risk.(Clinical Digest).” Nursing Standard 26.46 (2012): 16. Web. 4. Allen, Davis, Duke, Nonnemaker, Bradfield, and Farrelly. “New Product Trial, Use of Edibles, and Unexpected Highs among Marijuana and Hashish Users in Colorado.” Drug and Alcohol Dependence 176 (2017): 44-47. Web. 5. Cohn, Johnson, Ehlke, and Villanti. “Characterizing Substance Use and Mental Health Profiles of Cigar, Blunt, and Non-blunt Marijuana Users from the National Survey of Drug Use and Health.” Drug and Alcohol Dependence 160 (2016): 105-11. Web. 6. Amelia M. Arria, Kimberly M. Caldeira, Brittany A. Bugbee, Kathryn B. Vincent, Kevin E. O’Grady, Marijuana use trajectories during college predict health outcomes nine years post-matriculation, Drug and Alcohol Dependence, Volume 159, 2016, Pages 158-165. 7. Lisa Dierker, Arielle Selya, Stephanie Lanza, Runze Li, Jennifer Rose, Depression and marijuana use disorder symptoms among current marijuana users, Addictive Behaviors, Volume 76, 2018, Pages 161-168. |
| Exclusion List: | 1. Guttmannova, Kosterman, White, Bailey, Lee, Epstein, Jones, and Hawkins. “The essay writer Association between Regular Marijuana Use and Adult Mental Health Outcomes.” Drug and Alcohol Dependence 179 (2017): 109-16. Web. -excluded because it’s a longitudinal study that started with subjects in their adolescence; out of scope of age criteria 2. Joan S. Tucker, Anthony Rodriguez, Eric R. Pedersen, Rachana Seelam, Regina A. Shih, Elizabeth J. D’Amico, Greater risk for frequent marijuana use and problems among young adult marijuana users with a medical marijuana card, Drug and Alcohol Dependence, Volume 194, 2019. – excluded because it involves usage of medical marijuana, not “healthy” adults who use marijuana for recreational purposes 3. Villarosa‐Hurlocker, M. C., Bravo, A. J., Pearson, M. R. and , (2019), The Relationship Between Social Anxiety and Alcohol and Marijuana Use Outcomes Among Concurrent Users: A Motivational Model of Substance Use. Alcohol Clin Exp Re. doi:10.1111/acer.13966 – excluded because population of marijuana users also used alcohol; cannot isolate mental health effects of alcohol alone 4. Lisa Dierker, Arielle Selya, Stephanie Lanza, Runze Li, Jennifer Rose, Depression and marijuana use disorder symptoms among current marijuana users, Addictive Behaviors, Volume 76, 2018, Pages 161-168. – excluded because population already had a mental disorder (depression) which they were using marijuana for |
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| Author, Year, Study Design, Class Rating | Study Purpose | Study Population | Outcomes | Conclusion | Limitations |
| Buckner, Ecker, and Cohen, 2010 Case control study | The study set out to determine the effects of marijuana use on the mental health and academic performance of college students. | Undergraduate students; final N = 1,689 participants ages 18-54; undergraduate students in their sophomore or junior years with undeclared majors were targeted | – 29.2% of the sample reported use of marijuana – 19.4% reported infrequent (less than weekly) use and 9.8% endorsed frequent use (weekly use or greater) – There was a significant difference in the mean percentages of non-users, infrequent marijuana users, and frequent marijuana users in the prevalence of anxiety problems. | – There is a link between marijuana use and greater psychiatric impairment; more frequent marijuana use was positively correlated with greater academic difficulties and adverse mental health symptoms – For the most part, marijuana use (regardless of infrequent or frequent) was associated with greater mental health problems including anxiety, depression, hostility, interpersonal sensitivity, paranoia, psychoticism. | Many participants used alcohol concurrently with marijuana so it is possible mental health outcomes are affected more by alcohol than marijuana usageDesign does not allow relationship between variables to be observed as a cause-effect relationship |
| Weinberger et al., 2019 Cross-sectional study | To analyze the relationship between daily marijuana use and serious psychological distress | – “Daily cannabis users” were classified as those who indicated using cannabis on at least 25 days out of the past 30 (similar to other studies) – Data from current study came from the National Survey on Drug Use and Health public use data files for the years of 2008 to 2016 – Only data of persons 18 and older was included; Total sample for 2016 was N = 42,625 and the combined total sample for 2008 to 2016 was N = 356,413 | – The percentage of US adults who reported serious psychological distress increased over the study period from 4.78% in 2008 to 5.55% in 2016. This linear trend was significant. – In 2016, the prevalence of daily cannabis use was significantly higher among persons with past-month serious psychological distress versus those without past-month serious psychological distress | There is a relationship between the increasing use of cannabis in persons with serious psychological distress. Those with serious psychological distress are more likely to use cannabis every day than persons without serious psychological distress | – Because data was self-reported, there could be an underreporting of illegal behaviors such as cannabis use, errors in memory, or biases in reporting |
| Allen et al., 2017 | |||||
| Cohn et al., 2016 | |||||
| Amelia et al., 2016 | |||||
| Selva et al., 2018 |
| Buckner et al. | Weinberger et al. | Allen et al. | Cohn et al. | Amelia et al. | Selva et al. | ||
| Year | 2010 | 2019 | 2017 | 2016 | 2016 | 2018 | |
| Relevance Questions | |||||||
| 1 | N/A | N/A | |||||
| 2 | Yes | Yes | |||||
| 3 | Yes | Yes | |||||
| 4 | N/A | N/A | |||||
| Validity Questions | |||||||
| 1 | Yes | Yes | |||||
| 2 | Yes | Yes | |||||
| 3 | Yes | Yes | |||||
| 4 | Yes | Yes | |||||
| 5 | Yes | Yes | |||||
| 6 | No | Yes | |||||
| 7 | N/A | Yes | |||||
| 8 | Yes | Yes | |||||
| 9 | Yes | Yes | |||||
| 10 | N/A | Yes | |||||
| Quality Rating (+, 0, —) | + | + |
Evidence Analysis & Article Review
| Citation | Buckner, Ecker, and Cohen. “Mental Health Problems and Interest in Marijuana Treatment among Marijuana-using College Students.” Addictive Behaviors 35.9 (2010): 826-33. Web. |
| Study Design | Case Control Study |
| Class | |
| Quality Rating | + (Positive) |
| Research purpose | To determine the effects of marijuana usage on academic performance and mental health outcomes of college students |
| Inclusion criteria | Age: participants were between 18-54 Nutrition-related problem: marijuana usage Demographic: students with undeclared majors were targeted because students with undeclared majors are most likely to have academic difficulties and drop out (this study also looked at academic performance outcomes from usage of marijuana) |
| Exclusion criteria | Surveys that were incomplete or had questionable validity were discarded. This resulted in 456 survey responses to be discarded. |
| Description of Study Protocol | Recruitment: Undergraduate students were emailed a survey. Design Undergraduate students at a large public university in Southern Louisiana were approached via email survey to participate. Data were collected in February 2009.Two items from the Core Institute’s Campus Assessment of Alcohol and Other Drug Norms assessed perceived norms for frequency of marijuana use. Response options included daily, nearly every day, 2-3 times per week, 1 time per week, 2-3 times per month, 1 time per month, 3-6 times per year, 1-2 times per year, and never.The Marijuana Problems Scale (MPS) assessed negative social, occupational, physical, and personal consequences associated with marijuana use in the past 90 days.Participants were presented with a list of “different types of problems you may have experienced as a result of smoking marijuana”; the scale for rating the items was from 0 (no problem), 1 (minor problem) or 2 (serious problem).The Brief Symptom Inventory (BSI) is a self-report measure of psychiatric symptomatology. A Likert-like scale was used to assess the severity of the symptoms, from low severity to high severity as the numbers increased. |
| Data Collection Summary | Timing & Measurements The scales listed above were used to collect data. Students completed an online survey at surveymonkey.com Analyses Used Multivariate analysis of variance models (MANOVA) was conducted |
| Description of Actual Data Sample | Initial: 2,145 Attrition (final N): 1,689 Age: 18-54 Ethnicity: 8.1% African-American 4.0% Asian, 1.2% American Indian, 83.6% Caucasian, and 3.1% Hispanic/Latino Other relevant demographics: College-level education Location: United States (southern Louisiana) |
| Summary of Results | Key Findings: There was a significant difference in the mean percentages of non-users, infrequent marijuana users, and frequent marijuana users in the prevalence of anxiety problems. Non-users had a 9.56% reporting of anxiety symptoms, infrequent users had 10.25%, and frequent users had 10.37%. The p value was .005.There was also a significant difference in means with symptoms of depression, obsession/compulsions, hostility, paranoia, and more.12.22% of non-users reported depression symptoms, compared to 13.99% of infrequent users and 13.90% of frequent users. Other Findings: Nearly one-third of substance-using college students are interested in reducing or stopping their use |
| Author Conclusion | For the most part, marijuana use (regardless of infrequent or frequent) was associated with greater mental health problems including anxiety, depression, hostility, interpersonal sensitivity, paranoia, psychoticism. There were a few exceptions. Social anxiety was not found to be related to marijuana use status. |
| Reviewer Comments | Strengths This study used established symptom inventories that had strong internal validity and test-retest reliability. Findings were consistent with other studies about mental health outcomes and marijuana usage Weaknesses Many of the participants used alcohol concurrently with marijuana so it is unclear how much influence on mental health alcohol consumption had or if the health outcomes would have been different if only participants who only used marijuana were used |
| Funding Source | National Institute of Health; no conflicts of interest reported |
Quality Criteria Checklist
| Relevance Questions | ||
| 1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population studies? | 1 | N/A |
| 2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | 2 | Yes |
| 3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dietetics practice? | 3 | Yes |
| 4. Is the intervention or procedure feasible? (N/A for some epidemiological studies) | 4 | N/A |
| Validity Questions | ||
| 1. Was the research question clearly stated? 1.1 Was the specific intervention(s) or procedure (independent variable(s)) identified? 1.2 Was the outcome(s) (dependent variable(s)) clearly indicated? 1.3 Were the target population and setting specified? | 1 | Yes |
| 1.1 | Yes | |
| 1.2 | Yes | |
| 1.3 | Yes | |
| 2. Was the selection of study subjects/patients free from bias? 2.1 Were inclusion/exclusion criteria specified (e.g. risk, point in disease progression, diagnostic, or prognosis criteria), and with sufficient detail without omitting criteria critical to the study? 2.2 Were criteria applied equally to all study groups? 2.3 Were health, demographic, and other characteristics of subjects described? 2.4 Were the subjects/patients a representative sample of the relevant population? | 2 | Yes |
| 2.1 | No | |
| 2.2 | N/A | |
| 2.3 | Yes | |
| 2.4 | Yes | |
| 3. Were study groups comparable? 3.1 Was the method of assigning subjects/patients to groups described and unbiased? 3.2 Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? 3.3 Were concurrent controls used? (Concurrent preferred over historical controls.) 3.4 If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? 3.5 If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable. Criterion may not be applicable in some cross-sectional studies.) 3.6 If diagnostic test, was there any independent blind comparison with an appropriate reference standard? | 3 | N/A |
| 3.1 | N/A | |
| 3.2 | Yes | |
| 3.3 | No | |
| 3.4 | N/A | |
| 3.5 | No | |
| 3.6 | N/A |
| 4. Was method of handing withdrawals described? 4.1 Were follow up methods described and the same for all groups? 4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) 4.3. Were all enrolled subjects/patients (in the original sample) accounted for? 4.4. Were reasons for withdrawals similar across groups? 4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? | 4 | Yes |
| 4.1 | N/A | |
| 4.2 | Yes | |
| 4.3 | Yes | |
| 4.4 | N/A | |
| 4.5 | N/A | |
| 5. Was blinding used to prevent introduction of bias? 5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? 5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) 5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? 5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? 5.5. In diagnostic study, were test results blinded to patient history and other test results? | 5 | Unclear |
| 5.1 | N/A | |
| 5.2 | Yes | |
| 5.3 | N/A | |
| 5.4 | Unclear | |
| 5.5 | N/A | |
| 6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were intervening factors described? 6.1. In RCT or other intervention trial, were protocols described for all regimens studied? 6.2. In observational study, were interventions, study settings, and clinicians/provider described? 6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? 6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? 6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? 6.6. Were extra or unplanned treatments described? 6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? 6.8. In diagnostic study, were details of test administration and replication sufficient? | 6 | Yes |
| 6.1 | N/A | |
| 6.2 | Yes | |
| 6.3 | N/A | |
| 6.4 | N/A | |
| 6.5 | No | |
| 6.6 | No | |
| 6.7 | N/A | |
| 6.8 | N/A | |
| 7. Were outcomes clearly defined and the measurements valid and reliable? 7.1. Were primary and secondary endpoints described and relevant to the question? 7.2. Were nutrition measures appropriate to question and outcomes of concern? 7.3. Was the period of follow-up long enough for important outcome(s) to occur? 7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? 7.5. Was the measurement of effect at an appropriate level of precision? 7.6. Were other factors accounted for (measured) that could affect outcomes? 7.7. Were the measurements conducted consistently across groups? | 7 | Yes |
| 7.1 | Yes | |
| 7.2 | Yes | |
| 7.3 | N/A | |
| 7.4 | Yes | |
| 7.5 | Yes | |
| 7.6 | Yes | |
| 7.7 | Yes |
| 8. Was the statistical analysis appropriate for the study design and type of outcome indicators? 8.1. Were statistical analyses adequately described the results reported appropriately? 8.2. Were correct statistical tests used and assumptions of test not violated? 8.3. Were statistics reported with levels of significance and/or confidence intervals? 8.4. Was “intent to treat” analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? 8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? 8.6. Was clinical significance as well as statistical significance reported? 8.7. If negative findings, was a power calculation reported to address type 2 error? | 8 | Yes |
| 8.1 | Yes | |
| 8.2 | Yes | |
| 8.3 | Yes | |
| 8.4 | Yes | |
| 8.5 | Yes | |
| 8.6 | Yes | |
| 8.7 | N/A | |
| 9. Are conclusions supported by results with biases and limitations taken into consideration? 9.1. Is there a discussion of findings? 9.2. Are biases and study limitations identified and discussed? | 9 | Yes |
| 9.1 | Yes | |
| 9.2 | Yes | |
| 10. Is bias due to study’s funding or sponsorship unlikely? 10.1. Were sources of funding and investigators’ affiliations described? 10.2. Was there no apparent conflict of interest? | 10 | Yes |
| 10.1 | Yes | |
| 10.2 | Yes | |
| MINUS/NEGATIVE (-) If most (six or more) of the answers to the above validity questions are “No,” the report should be designated with a minus (-) symbol on the Evidence Worksheet.. |
| Citation | Andrea H. Weinberger, Lauren R. Pacek, Christine E. Sheffer, Alan J. Budney, Joun Lee, Renee D. Goodwin, Serious psychological distress and daily cannabis use, 2008 to 2016: Potential implications for mental health?, Drug and Alcohol Dependence, Volume 197, 2019, Pages 134-140. |
| Study Design | Cross-sectional study |
| Class | |
| Quality Rating | + (Positive) |
| Research purpose | To determine the relationship between daily cannabis use and serious psychological distress (SPD). |
| Inclusion criteria | Age: participants were between 18-54 Nutrition-related problem: marijuana usage Demographic: since data came from the National Survey on Drug Use and Health public use data files for the years of 2008 to 2016, researchers only used data from respondents age 18 and over |
| Exclusion criteria | Any respondents under the age of 18 were excluded from the sample size. |
| Description of Study Protocol | Recruitment: Preexisting data from the National Survey on Drug Use and Health public use data files for the years 2008 – 2016 Design |
| Data Collection Summary | Definitions & Measurements Daily cannabis use was classified as using cannabis on at least 25 out of the past 30 days (similar to other studies)Serious psychological distress (SPD) was assessed using the Kessler Psychological Distress Scale (K6) screening instrument which is a 6-item scale that assesses frequency of feeling nervous; hopeless; restless or fidgety; sad or depressed; that everything is an effort; or feeling down on oneself, no good, or worthless.Respondents were classified into one or two non-overlapping groups: past-month SPD (respondents who met the critical score of 13 or more for SPD) and no SPD (respondents who did not meet criteria for SPD in the past month) Analyses Used Linear time trends of daily cannabis use were assessed using logistic regression models with continuous year as the predictorMultivariable logistic regression was used to adjust for demographics and heavy alcohol use |
| Description of Actual Data Sample | Total Sample for 2016: 42,625 Combined Total Sample from 2008 to 2016: 356,413 Age: 18 and older Ethnicity: Not specified Other relevant demographics: Respondents from all 50 states Location: United States |
| Summary of Results | Key Findings The percentage of US adults who reported serious psychological distress increased over the study period from 4.78% in 2008 to 5.55% in 2016. This linear trend was significant.In 2016, the prevalence of daily cannabis use was significantly higher among persons with past-month serious psychological distress versus those without past-month serious psychological distress Other Findings There were significant increases in the prevalence of past-month daily cannabis use among persons with and without past-month SPDThese increasing trends remain significant after adjusting for demographics and heavy alcohol useThere was no significant interaction of time and SPD status suggesting that the increase in cannabis use prevalence over time was similar among those with and without SPD. |
| Author Conclusion | Daily cannabis use is significantly more common among persons with SPD and is increasing in this group, as well as among those without. This could have serious implications on the increased affinity for mental health vulnerabilities. |
| Reviewer Comments | Strengths The time passed, demographics, and past-month SPD and no SPD were all adjusted for. Weaknesses Because data was self-reported, there could be an underreporting of illegal behaviors such as cannabis use, errors in memory, or biases in reporting. |
| Funding Source | National Institute of Health; no conflicts of interest reported |
| Relevance Questions | ||
| 1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population studies? | 1 | N/A |
| 2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | 2 | Yes |
| 3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dietetics practice? | 3 | Yes |
| 4. Is the intervention or procedure feasible? (N/A for some epidemiological studies) | 4 | N/A |
| Validity Questions | ||
| 1. Was the research question clearly stated? 1.1 Was the specific intervention(s) or procedure (independent variable(s)) identified? 1.2 Was the outcome(s) (dependent variable(s)) clearly indicated? 1.3 Were the target population and setting specified? | 1 | Yes |
| 1.1 | Yes | |
| 1.2 | Yes | |
| 1.3 | Yes | |
| 2. Was the selection of study subjects/patients free from bias? 2.1 Were inclusion/exclusion criteria specified (e.g. risk, point in disease progression, diagnostic, or prognosis criteria), and with sufficient detail without omitting criteria critical to the study? 2.2 Were criteria applied equally to all study groups? 2.3 Were health, demographic, and other characteristics of subjects described? 2.4 Were the subjects/patients a representative sample of the relevant population? | 2 | Yes |
| 2.1 | Yees | |
| 2.2 | Yes | |
| 2.3 | Yes | |
| 2.4 | Yes | |
| 3. Were study groups comparable? 3.1 Was the method of assigning subjects/patients to groups described and unbiased? 3.2 Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? 3.3 Were concurrent controls used? (Concurrent preferred over historical controls.) 3.4 If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? 3.5 If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable. Criterion may not be applicable in some cross-sectional studies.) 3.6 If diagnostic test, was there any independent blind comparison with an appropriate reference standard? | 3 | Yes |
| 3.1 | Yes | |
| 3.2 | Yes | |
| 3.3 | Yes | |
| 3.4 | Yes | |
| 3.5 | N/A | |
| 3.6 | N/A |
| 4. Was method of handing withdrawals described? 4.1 Were follow up methods described and the same for all groups? 4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) 4.3. Were all enrolled subjects/patients (in the original sample) accounted for? 4.4. Were reasons for withdrawals similar across groups? 4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? | 4 | N/A |
| 4.1 | N/A | |
| 4.2 | N/A | |
| 4.3 | Yes | |
| 4.4 | N/A | |
| 4.5 | N/A | |
| 5. Was blinding used to prevent introduction of bias? 5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? 5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) 5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? 5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? 5.5. In diagnostic study, were test results blinded to patient history and other test results? | 5 | Yes |
| 5.1 | N/A | |
| 5.2 | N/A | |
| 5.3 | N/A | |
| 5.4 | N/A | |
| 5.5 | N/A | |
| 6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were intervening factors described? 6.1. In RCT or other intervention trial, were protocols described for all regimens studied? 6.2. In observational study, were interventions, study settings, and clinicians/provider described? 6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? 6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? 6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? 6.6. Were extra or unplanned treatments described? 6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? 6.8. In diagnostic study, were details of test administration and replication sufficient? | 6 | Yes |
| 6.1 | N/A | |
| 6.2 | Yes | |
| 6.3 | N/A | |
| 6.4 | N/A | |
| 6.5 | No | |
| 6.6 | No | |
| 6.7 | N/A | |
| 6.8 | N/A | |
| 7. Were outcomes clearly defined and the measurements valid and reliable? 7.1. Were primary and secondary endpoints described and relevant to the question? 7.2. Were nutrition measures appropriate to question and outcomes of concern? 7.3. Was the period of follow-up long enough for important outcome(s) to occur? 7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? 7.5. Was the measurement of effect at an appropriate level of precision? 7.6. Were other factors accounted for (measured) that could affect outcomes? 7.7. Were the measurements conducted consistently across groups? | 7 | Yes |
| 7.1 | Yes | |
| 7.2 | Yes | |
| 7.3 | N/A | |
| 7.4 | Yes | |
| 7.5 | Yes | |
| 7.6 | Yes | |
| 7.7 | Yes |
| 8. Was the statistical analysis appropriate for the study design and type of outcome indicators? 8.1. Were statistical analyses adequately described the results reported appropriately? 8.2. Were correct statistical tests used and assumptions of test not violated? 8.3. Were statistics reported with levels of significance and/or confidence intervals? 8.4. Was “intent to treat” analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? 8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? 8.6. Was clinical significance as well as statistical significance reported? 8.7. If negative findings, was a power calculation reported to address type 2 error? | 8 | Yes |
| 8.1 | Yes | |
| 8.2 | Yes | |
| 8.3 | Yes | |
| 8.4 | N/A | |
| 8.5 | Yes | |
| 8.6 | Yes | |
| 8.7 | N/A | |
| 9. Are conclusions supported by results with biases and limitations taken into consideration? 9.1. Is there a discussion of findings? 9.2. Are biases and study limitations identified and discussed? | 9 | Yes |
| 9.1 | Yes | |
| 9.2 | Yes | |
| 10. Is bias due to study’s funding or sponsorship unlikely? 10.1. Were sources of funding and investigators’ affiliations described? 10.2. Was there no apparent conflict of interest? | 10 | Yes |
| 10.1 | Yes | |
| 10.2 | Yes | |
| MINUS/NEGATIVE (-) If most (six or more) of the answers to the above validity questions are “No,” the report should be designated with a minus (-) symbol on the Evidence Worksheet.. |
