AHRQ Report on Meditation Techniques Walton Review

Transcription

1 Critique of Meditation Practices for Health: State of the Research Kenneth Walton, Ph.D. Conducted at the request of University of Alberta Evidence Based Practice Center Page 1

2 I. CHAPTER 2. METHODS I.A. Critique On p. 18 under Databases and search terms, Scientific Research on the Transcendental Meditation Program: Collected Papers (Volumes 1 to 4), was listed as a journal, which was included in the search. There are two problems with this: 1) This is not a journal, but is a series of volumes of anthologies of research papers, including papers reprinted from over 100 peer-reviewed journals in different fields; 2) The search should have included Vol. 5 of the Collected Papers, which was published in 1990, and which is available through interlibrary loan as well as from Amazon.com. I.A.1. COMMENT The 75 papers published in Volume 5 should be included in the review. Most of the papers reprinted there were incorrectly excluded. I.A.2. DISCRETIONARY REVISION 1) Include in the review Volume 5 of Scientific Research on the Transcendental Meditation Program: Collected Papers. (I sent the authors a complimentary copy). 2) Correct through out the review that this is a research anthology (instead of a journal) and format the references accordingly, i.e., as papers appearing in an edited book. 3) For all papers that were originally published in journals, cite the primary journal reference, not the secondary reference to the Collected Papers. Appraisal of Studies I.B. Critique 1: Inappropriateness of Jadad scores for research on meditation techniques On page 20 it is stated that the Jadad scale was used to assess the methodological quality of research studies, but this scale in its original form is inappropriate for research on meditation techniques, as the authors admit on page 191, paragraph 3, and gives a misleading impression of the overall quality of meditation research. Furthermore, use of this scale does not give due recognition to studies that are single blinded. I.B.1. COMMENT Based to a large extent upon Jadad criteria, the report concludes (e.g., p. 100) that meditation studies are mostly of low quality. However, the Jadad scale was developed based on trials for pain treatment, where placebo controls are often easily constructed. The standard Jadad scale appears less appropriate for behavioral interventions, where the subjective participation of the patient may be important, and true double blinding is not possible. In the Jadad scale, two out of five points are awarded for double blinding, including its adequate description, but no credit is given for single blinding (concealing subjects treatment group membership from test administrators). As the report notes on page 191, paragraph 3: Some treatments cannot be tested in a double blinded fashion according to the principles of Western science dictates. On page 20 the AHRQ researchers state that they modified the Jadad scale for NRCT s. Likewise the Jadad scale could be modified to set an appropriate standard for what is generally feasible methodology in meditation RCTs. Single blinding of the test administrators/data collectors and controlling for subject expectancy (i.e. structuring control interventions to involve identical attention from instructors and testers, administration of instruments to gauge expectation) should be taken into account by the modified scale. Page 2

3 I.B.2. AHRQ Report on Meditation Techniques Walton Review MAJOR COMPULSORY REVISION A modified Jadad score should be calculated for all studies in which the double blinding criteria are replaced with blinding of testers/data collectors (single blinded). Points should also be awarded for whether equal time, attention, and expectancy of benefits are given to both the intervention and the control groups. Data Synthesis I.C. Assumptions, Statistical Procedures, and Interpretation of Meta-Analyses: Topics III and V I.C.1. CRITIQUE Critical methodological details of the meta-analytic procedures, such as the underlying assumptions and statistical procedures used in the meta-analyses, are not sufficiently described. More attention also is needed on the methods used in interpreting results. I.C.2. MAJOR COMPULSORY REVISIONS The statistical approaches used in the meta-analyses should be more completely described and justified, as follows: 1. A more detailed description of the methods should include an explanation of the statistical assumptions of each of the methods employed. 2. Prior to the reporting of meta-analysis findings in each section, there should be an analysis of the degree to which the data being included in the meta-analysis fit the statistical assumptions of the meta-analysis procedures. This is true both for the general approach and for the indirect comparisons procedure. 3. For each meta-analytic statistical estimate of change or difference between procedures for which statistical significance (type-i error) is being reported, an estimate of the statistical power (or conversely, of type-ii error) should also be reported. This is particularly crucial given the small number of studies being used in each comparison. The issue of using meta-analytic procedures with as few as two studies is raised (p. 199) and justified by the authors by stating that this should provide a better estimate of effects than single studies. Nevertheless, when inferences are being made on the basis of such small study numbers, the authors should be obliged to provide statistical power estimates so that the readers can judge in each case the adequacy of the basis on which inferences are being made. 4. An additional broad concern about the way the meta-analysis results are reported is that the consideration of possible sources of heterogeneity in cases where the sample of study results is not homogeneous is often highly speculative, given that the number of dimensions along which the studies differ is frequently larger than the number of studies available. This could be addressed by adopting a criterion in this regard, such as only suggesting possible sources of heterogeneity when the number of studies in the analysis is more than ten. I.D. Structured Format and Peer Review Process (pages 24, 25) I.D.1. CRITIQUE The steps of the peer review process are not adequately described in the text, and the process described to this reviewer in communications from the authors is not an adequate peer review. I.D.2. COMMENT The Structured Format for Peer Reviewers states that Major Compulsory Revisions are Revisions that the author must respond to before a decision on publication can be reached. This is standard for peer-reviewed journals. It is generally the case that peer-reviewed journals make sure that the peer reviewers are satisfied with the authors responses to major compulsory revisions before a paper is accepted for publication. It is especially important to adhere to this high standard in the current report on meditation techniques, because the reviewers have expertise in specific areas of research and methodology that a general editor may not possess. Moreover, this report, coming as it does from NIH/AHRQ, will have important national policy implications. Therefore even greater care than ordinary should be taken to fully utilize the Page 3

4 reviewers comments to overcome any serious deficiencies in the report, which the reviewers were mandated to address with their comments. Failure to do this would not be genuinely utilizing the peer-review process, which could result in a seriously flawed report. I.D.3. MAJOR COMPULSORY REVISIONS: The authors responses to the Major Compulsory Revisions must be sent to the peer reviewers and the peer reviewers must sign off that the revisions were satisfactorily made prior to the decision that the report is ready for publication. II. CHAPTER 3. RESULTS III. CHAPTER 3. TOPIC III: EVIDENCE FOR THE EFFICACY AND EFFECTIVENESS OF MEDITATION HYPERTENSION STUDIES WITH BP AS OUTCOME STUDY SELECTION 1. Inclusion/Exclusion Criteria Inclusion of only hypertensive subjects III.A. Critique Page 99 states: All studies were conducted in patients with a diagnosis of essential hypertension. All studies in this section should meet commonly accepted criteria for hypertension such as the JNC VII definition of hypertensive subjects (i.e., SBP=>140 mm Hg and/or DBP=>90 mm Hg as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure--JNC VII), Chobanian et al., JAMA. 2003; 289. Those studies that have included (nonhypertensive) subjects should be excluded from this section. III.A.1. MAJOR COMPULSORY REVISION: According to Appendix H, characteristics of clinical trials of meditation in hypertension, and a review of the original manuscripts, the following studies included subjects who were not hypertensive and should be excluded from the Topic III, Hypertension section: a. Castillo-Richmond 2000 b. Calderon 2000, (This study should be excluded for a second reason, i.e., it duplicates the Castillo- Richmond 2000 sample. c. Tsai 2003 (Since this is the only study on Tai Chi, the category of Tai Chi should be deleted from this section.) 2. Inclusion/Exclusion Criteria Non-independent, Overlapping Samples III.B. Critique Studies are included in this section whose samples are not independent samples. They are either substudies or have overlapping samples with other trials (see p. 107). III.B.1. MAJOR COMPULSORY REVISION Delete the following studies from this section that do not include independent samples. a. Kondwani 1998: Kondwani 1998, later published in the Journal of Social Behavior and Personality, 2005, 17, , is a sub-study of Schneider 2005 and should be excluded (see Kondwani, 2005, pg. 184). b. Calderon 2000: The Calderon 2000 subjects are from the same study as Castillo-Richmond Castillo-Richmond 2000 is the better of the two studies in terms of design (Jadad score of 3) and is published in a peer-reviewed heart journal (Stroke American Heart Association). The Calderon 2000 study is published as a dissertation and has a Jadad score of 1. Page 4

5 3. Inclusion/Exclusion: Incorrect Classifications III.C. Critique The study by Seer and Raeburn 1980 (see p. 99 and ref #214) did not use the Transcendental Meditation program. The authors point out that their study involved a newly invented form of meditation that they call SRELAX. Please note that the teaching of the Transcendental Meditation technique is only given in a fully standardized way by teachers certified by Maharishi Vedic Education Development Corp. III.C.1. MAJOR COMPULSORY REVISION Delete the Seer and Raeburn 1980 study from the Transcendental Meditation studies. III.D. Critique The study by Yen 1996 (see p. 120) was not specifically on Zen Buddhist meditation. The intervention used involved progressive muscle relaxation with performance in Buddhist meditation being optional. III.D.1. MAJOR COMPULSORY REVISION Delete the Yen 1996 study from the category of Zen Buddhism since it is mainly PMR and not clearly specified as Zen Buddhist meditation. With only one study remaining in this category, the direct comparison analysis should be deleted and conclusions originally stated about this category in the report should be correspondingly changed. 4. Inclusion/Exclusion of before-and-after studies on hypertensive subjects III.E. Critique Table 3 on pg. 19 shows the inclusion criteria for Topics II to V. Table 3 also indicates that before-and-after studies are included in topic V but are not included in topic III. Study designs across data sections should be consistent in order to avoid being arbitrary and potentially biased. Therefore before-and-after studies should be included in topic II as well as topic V. III.E.1. MAJOR COMPULSORY REVISION Include the following before-and-after studies in topic III, because these studies are also on hypertensive patients: a. Agarwal, BL and Kharbanda, A. Effects of Transcendental Meditation on mild and moderate hypertension. Scientific Research on Maharishi s Transcendental Meditation and TM-Sidhi Programme- Collected Papers. Vol. 3. Switzerland: MERU: MVU Press, , (currently in topic V) b. Benson, H, Rosner, BA, Marzetta et al. Decreased blood pressure in borderline hypertensive subjects who practiced meditation. J Chronic Dis, 27(3): , (currently in topic V) c. Benson H, Rosner BA, Marzetta, BR Lemchuk, HM, Decreased blood pressure in pharmacologically treated hypertensive patients who regularly elicited the relaxation response. Lancet 1, , 1974 d. Benson H, Wallace RK, Decreased blood pressure in hypertensive subjects who practiced meditation. Circulation 45/46 Supp. 526, 1972 e. Pollack, AA, Case, DB, Weber, MA et al.. Limitations of Transcendental Meditation in the treatment of essential hypertension. Lancet, 1(8002):71-73, (currently in topic V) 5. Inclusion/Exclusion of studies on children III.F. Critique Research on children is excluded. This probably violates NIH policy on including children in research. III.F.1. COMMENT According to the NIH (NIH policy and guidelines on the inclusion of children as participants in research involving human subjects, March 6, 1998) It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all NIH conducted or supported research involving human subjects. Page 5

6 III.F.2. MAJOR COMPULSORY REVISION Include the following studies by Barnes on adolescents in this section: a. Barnes VA, Treiber FA, Davis H. Impact of Transcendental Mediation on cardiovascular function at rest and during acute stress in adolescents with high normal blood pressure. J Psychosom Res 2001;51: b. Barnes VA, Treiber FA, Johnson MH. Impact of Transcendental Meditation on ambulatory blood pressure in African- American adolescents. Am J Hypertens 2004;17: STUDY IDENTIFICATION III.G. Critique The Alexander et al. (1989) RCT on meditation modalities in subjects with high BP (average 140 mm Hg) should be included under BP outcomes. III.G.1. MAJOR COMPULSORY REVISION Alexander 1989 (Alexander C.N., E.J. Langer, R.I. Newman, H.M. Chandler and J.L. Davies, Transcendental Meditation, mindfulness, and longevity: an experimental study with the elderly. Journal of Personality and Social Psychology, (6): p ) should be included in either topic III or topic V. The study was already included under the verbal fluency subsection in topic V under the reference: Alexander, Davies et al., 1991, in Maharishi s Transcendental Meditation and TM-Sidhi programme Collected Papers, vol. 4 (reference #271). DATA COLLECTION III.H. Critique: Report of funding and withdrawals/dropouts Table 24 (pg. 103) has information missing for the following categories: a) report of funding and b) description of withdrawals/dropouts. III.H.1. MAJOR COMPULSORY REVISION: Provide the following information in this table and change the Jadad score for Castillo Richmond to 3. a. Schneider yes, reported funding. b. Schneider yes, reported funding. c. Castillo Richmond yes, reported funding and describes withdrawals and dropouts in the study III.I. Critique: Incorrect statement regarding BP change and the TM technique Pg. 108 incorrectly states that the study with the shortest duration (3 mos) was the only trial that reported statistically significant changes in DBP favoring TM. Schneider et al also found a one-year significant reduction in DBP for the TM technique compared vs. controls. III.I.1. MAJOR COMPULSORY REVISION The above statement should be changed, showing that trials of both 3-month (Schneider 1995) and one-year (Schneider 2005) duration indicated significant reductions in BP with TM. DATA SYNTHESIS III.J. Critique: Need for modified Jadad scoring for meditation studies Page 6

7 III.J.1. COMMENT AHRQ Report on Meditation Techniques Walton Review Jadad scores indicate that the preponderance of meditation studies is of low quality. Jadad scores emphasize doubleblinding, which is extremely difficult to attain in meditation research. Because of the very low percentage of double-blinded studies in this report, studies that are single blinded should be given improved Jadad scores. (See also critique under Methods.) III.J.2. MAJOR COMPULSORY REVISIONS Re-score all studies using a modified Jadad scoring system in which double-blinding is replaced with single-blinding. For those studies that are single-blinded, this will result in a higher modified Jadad score, approximately 2 points higher. For all analyses, studies should be separated by low and high Jadad scores (<3 vs. >=3) and results should be clearly reported according to these separate groups. III.K. Critique: Misinterpretation of mixed treatment comparisons Tables 26 & 27, Figures 25 & 26 give a misleading impression of which techniques in relation to NT have the highest likelihood of being the best technique. III.K.1. COMMENT Although the authors acknowledge on page 23 that statistical power in the hypertension mixed treatment meta-analysis is low and cite in numerous places in the report that the quality of the studies is low, the authors give the impression that it can be determined which technique has the highest probability of being the most effective in reducing BP in hypertensive patients. The technique rated as the best technique, Tai Chi, has only one study and that being with prehypertensive subjects. Other technique categories such as Qi Gong and Yoga (and Tai Chi) involve exercise as a major component and therefore substantially confound any meditation effect that there may be from these interventions. From a purely statistical standpoint, ranking 15 treatments entails over 100 pairwise comparisons among the treatments, significantly elevating type I error. III.K.2. MAJOR COMPULSORY REVISIONS: Delete the last column of Tables 26 & 27 on the probability of best practice. IV. CHAPTER 3. TOPIC III. EVIDENCE OF THE EFFICACY AND EFFECTIVENESS OF MEDITATION HYPERTENSION STUDIES WITH OUTCOMES OF BODY WEIGHT, HEART RATE, STRESS, ETC. STUDY SELECTION 1. Inclusion/Exclusion Criteria Hypertensive patients IV.A. Critique Mixing results from hypertensive subjects with results from non-hypertensive subjects IV.A.1. COMMENT Appendix H: Characteristics of clinical trials of meditation in hypertension, and a review of the literature, indicate that the studies listed below included nonhypertensive subjects. These two studies were included in the direct comparison of TM vs. HE in this section on hypertensive subjects and should be excluded. a. Castillo-Richmond 2000 b. Calderon 2000 (also overlaps with the Castillo-Richmond sample, see HTN Study Selection inclusion/exclusion criteria #2 above) Page 7

8 IV.A.2. AHRQ Report on Meditation Techniques Walton Review MAJOR COMPULSORY REVISION This entire section comparing TM to HE on body weight, heart rate, stress, anger, self-efficacy, dietary intake, and physical activity; pgs should be deleted since the Castillo-Richmond 2000 and Calderon 2000 studies include nonhypertensive patients and do not meet the criteria for being hypertension studies. Only the one Kondwani 1998/2005 study remains (substudy of Schneider 2005) which is not enough for a meta-analysis according to the criteria on pg. 104: Direct meta-analyses were conducted when two or more studies were of the same genre; that is to say, they assessed the same type of meditative technique, used similar comparison groups and had usable data for common outcomes of interest. 2. Inclusion/Exclusion Criteria: Mortality as important outcome in hypertensive subjects IV.B. Critique The clinical endpoint mortality with hypertensive patients should be included as an outcome in the HTN section. IV.B.1. MAJOR COMPULSORY REVISION There are two important RCTs on mortality in hypertensive subjects practicing Transcendental Meditation. Schneider 2005 (see below) published a pooled long-term follow-up of both of the following studies (a. Schneider, Staggers et al., A randomized controlled trial of stress reduction for hypertension in older African Americans. Hypertension, 1995, 26(5): and b. Alexander, C.N., E.J. Langer, R.I. Newman, H.M. Chandler and J.L. Davies, Transcendental Meditation, mindfulness, and longevity: an experimental study with the elderly. Journal of Personality and Social Psychology, (6): p ) There were two trials here, so a meta-analysis should be done on this long-term clinical outcome. Reference: Schneider R.H., Alexander C.N., Staggers F., Rainforth M., Salerno J.W., Hartz A., Arndt S., Barnes V.A., Nidich S.I. Long-term effects of stress reduction on mortality in persons 55 years of age with systemic hypertension: American Journal of Cardiology, 95: , V. CHAPTER 3. TOPIC III: EVIDENCE FOR THE EFFICACY AND EFFECTIVENESS OF MEDITATION: SUBSTANCE ABUSE STUDY SELECTION V.A. Overall Critique: No meta-analyses were conducted on substance usage due to the dissimilarity with respect to the type of meditation technique, comparison group and data for common outcome of interest. V.A.1. COMMENT: The study inclusion criteria should be expanded to include all studies with any of the following substance usage outcomes: non-prescribed drug use, alcohol use, or cigarette smoking/tobacco use. The studies should not be limited only to patients who are substance abusers or have a history of substance abuse. Patients with a formal medical diagnosis of Substance abuse or substance abuse disorder are only a small subset of all individuals who use alcohol, cigarettes or other non-prescribed drugs. V.A.2. MAJOR COMPULSORY REVISION: All of the studies listed below should be included in this section and meet the following criteria: 1) primary research reports; 2) sample sizes greater than 10; 3) measurable data for health-related substance usage; and 4) study designs which are either RCTs, NRCTs, or B&As (Table 3: Inclusion Criteria for topics II to V, pg. 19). See argument for inclusion of beforeand after designs given below. 1. Inclusion/exclusion criteria: RCT and NRCT studies on substance usage a. Brooks, J.S. and T. Scarano, Transcendental Meditation in the Treatment of Post-Vietnam Adjustment. Journal of Counseling and Development, : p RCT, alcohol consumption Page 8

9 b. Katz, D (1977) Decreased drug use and prevention of drug use through the Transcendental Meditation program. In DW Orme-Johnson and JT Farrow (Eds) Scientific Research on the Transcendental Meditation program: Collected Papers, volume 1, (pp ) Rheinweiler, Germany: Maharishi European Research University Press. NRCT, marijuana use, alcohol use c. Nidich S, (1989) The Science of Creative Intelligence and the Transcendental Meditation program: Reduction of drug and alcohol consumption. In RA Chalmers, G Clements, H Schenkluhn and M Weinless (Eds), Scientific Research on the Maharishi s Transcendental Meditation and TM-Sidhi Program: Collected Papers, volume 3 (pp ) Vlodrop, The Netherlands: Maharishi Vedic University Press. NRCT, marijuana use, alcohol use d. Alexander, CN, Swanson, GC, Rainforth M, Carlisle, TW, Todd, CC, and Oates, RM. Effects of the Transcendental Meditation program on stress reduction, health, and employee development: a prospective study in occupation settings. Anxiety, Stress, and Coping, 6: , NRCT, alcohol and cigarette smoking. e. Myers, T.I. & Eisner, E.J. (1974) An experimental evaluation of the effects of karate and meditation. Final report for the U.S. Army Institute for the Behavioral and Social Sciences, Social Processes Technical Area. Washington, DC: American Institutes for Research. RCT, drug use f. Ottens, A.J., The effect of transcendental meditation upon modifying the cigarette smoking habit. Journal of the School of Health, (10): p RCT, cigarette smoking 2. Inclusion/exclusion criteria: before-and-after (BA) studies on substance usage (Before-and-after studies should be included in topic III as well as topic V no reason is given why BA designs are included in one section of this report and not in another that employs the same statistical methodology) a. Lazar Z, Farwell L and Farrow JT (1977) The effects of the Transcendental Meditation program on anxiety, drug abuse, cigarette smoking and alcohol consumption. In DW Orme-Johnson and JT Farrow (Eds) Scientific Research on the Transcendental Meditation program: Collected Papers, volume 1, (pp ) Rheinweiler, Germany: Maharishi European Research University Press. BA, marijuana use, drug use, alcohol and cigarette use b.takashi Haratani and Takkemitsu Hemmi, Effects of Transcendental Meditation on the health behaviour of industrial workers, Japanese Journal of Public Health 37 (10 Suppl.): 729, BA, cigarette smoking c. Royer, A., The role of the Transcendental Meditation Technique in promoting smoking cessation; a longitudinal study, in Self Recovery Treating Addictions Using Transcendental Meditation and Maharishi Ayur-Veda, D.F. O'Connell and C.N. Alexander, Editors. 1994, Harrington Park Press: Binghamton, NY. p BA, tobacco use 3. Inclusion/exclusion criteria: exclusion of study without substance usage outcome The following study originally included in this section should be deleted since it does not include data on substance usage: a. Ramirez J. The Transcendental Meditation program as a possible treatment modality for drug offenders: evaluation of a pilot project at Milan Federal Correctional Institution. In: Chalmers RA, Clements G, Schenkluhn H, et al., eds. Sci Res Maharishi's Transcendental Meditation and TM-Sidhi Programme - Collected papers. Vol. 2. Switzerland: Maharishi European Research University - MVU Press; p VI. CHAPTER 3: TOPIC V: EVIDENCE ON THE PHYSIOLOGICAL EFFECTS OF MEDITATION TECHNIQUES The following 10 outcome measures for physiological effects of the Transcendental Meditation technique are reviewed in the order in which they are listed on page 153. VI.A. Cardiovascular functioning Outcome Measure: Blood Pressure Page 9

10 STUDY SELECTION 1. Studies Incorrectly Excluded AHRQ Report on Meditation Techniques Walton Review The following studies included healthy subjects in trials of Transcendental Meditation program and blood pressure. They should be included in the Fig. 22. Meta-analysis of effects of TM versus NT on blood pressure. a. Broome, J.R.N., Orme-Johnson, D.W., Schmidt-Wilk, J. (2005). Worksite stress reduction through the Transcendental Meditation program. Journal of Social Behavior and Personality, 17, b. Wenneberg, S.R., Schneider, R.H., Walton, K.G., MacLean, C.R.K., Levitsky, D.K., Salerno, J.W., Wallace, R.K., Mandarino, J.V., Rainforth, M.V., Waziri, R.: A controlled study of the effects of the Transcendental Meditation program on cardiovascular reactivity and ambulatory blood pressure. Internat J Neurosci 89, 15-28, 1997 c. Bagga OP, Gandhi A. A comparative study of the effect of transcendental meditation (TM) and shavasana practice on cardiovascular system. Indian Heart J 1983;35(1): d. Alexander, C.N., E.J. Langer, R.I. Newman, H.M. Chandler and J.L. Davies, Transcendental Meditation, mindfulness, and longevity: an experimental study with the elderly. Journal of Personality and Social Psychology, (6): p Note: The trial by Alexander, 1989 included hypertensive and normotensive subjects. It might be best to include it in Topic III on hypertension. However, Topic V would be a second choice. Trials on adolescents should be included Note: As every applicant for NIH research grants knows, the NIH has required all applicants to avoid ageism in health studies for the past 9 years. It is ageism to not include relevant studies on mediation and BP done in individuals less than 18 years of age. Therefore the following trials by Barnes and colleges should be included in this topic on BP. Barnes VA, Treiber FA, Davis H. Impact of Transcendental Mediation on cardiovascular function at rest and during acute stress in adolescents with high normal blood pressure. J Psychosom Res 2001;51: Barnes VA, Treiber FA, Johnson MH. Impact of Transcendental Meditation on ambulatory blood pressure in African- American adolescents. Am J Hypertens 2004;17: The following study should be excluded from the Topic III on BP Note: The study by Fields 2002 was not designed as a study of meditation per se. The methods clearly indicate that it was a study of a traditional system of medicine that included Vedic diet, exercise, herbal supplements and the TM technique. Therefore it should be removed from the meditation alone and BP section. If there is a section on composite interventions including the TM technique, it may be included there. Fields, JZ, Walton KG, Schneider RH, et al Am J Cardiol, :952-8 The following before and after studies on TM and blood pressure in healthy subjects should be included. Lovell-Smith HD, Dickie A, Robinson J, Blood pressure and plasma cholesterol levels before and after learning Transcendental Meditation, In Chalmers R et al (Eds) Scientific research on Maharishi s Transcendental Meditation and TM-Sidhis programme, Collected Papers Vol. 2, pp , 1989 Note: This study included both normotensive and hypertensive subjects. The following before and after studies on TM and blood pressure should be excluded from this section. Note: All these studies were on hypertensive subjects. Move to Topic III on Hypertension. Agarwal 1990 Benson 1974a, (Journal of Chronic Diseases) Pollack 1977 Add the following before and after studies to Topic III on Hypertension. Note: All these studies were on hypertensive subjects. Page 10

11 Benson H, Wallace RK, Decreased blood pressure in hypertensive subjects who practiced meditation. Circulation 45/46 Supp. 526, 1972 Benson H, Rosner BA, Marzetta, BR Lemchuk, HM, Decreased blood pressure in pharmacologically treated hypertensive patients who regularly elicited the relaxation response. Lancet 1, , 1974 [Benson, 1974b] DATA SYNTHESIS AND DISCUSSION VI.A.1. CRITIQUE The three before and after studies on hypertensive subjects-- Agarwal, 1990, Benson, 1974, and Pollack, (see Figure 32, page 163) in topic V, as stated by the authors (pg. 162) have a combined estimate of change from baseline in SBP of mm Hg and in DBP of 6.86 mm Hg, indicating a small, significant improvement (reduction) favoring TM. This judgmental statement is incorrect. According to JNC VII (Chobanian, 2003, ttp:// these degrees of BP reduction are similar to those produced by many BP drugs and would result in highly clinically significant reductions in cardiovascular morbidity and mortality. VI.A.2. MAJOR COMPULSORY REVISION Change wording on page 162, last paragraph, to read: indicating a statistically and clinically significant improvement (reduction) favoring TM. VI.B. Pulmonary Functioning a. DILLBECK, M. C., and ORME-JOHNSON, D. W. Physiological differences between Transcendental Meditation and rest. American Psychologist 42: , (Paper # 356 in Collected Papers) Higher Basal Skin Resistance; Lower Respiration Rate; Lower Plasma Lactate. Lower Baseline Levels of Spontaneous Skin Resistance Responses, Respiration Rate, Heart Rate, and Plasma Lactate. Adults, Meta-Analysis of 32 Studies Not cited. All the studies in this meta-analysis should be included in the review but currently are not. b. GALLOIS, P. Modifications neurophysiologiques et respiratoires lors de la pratique des techniques de relaxation. L Encéphale 10: , (Paper #358 in CP) Lower Heart Rate; Decreased Breath Rate; Episodes of Spontaneous Respiratory Suspension (Without Compensatory Hyperventilation). Increased Alertness: Faster Reaction Time after the Practice. Lower Heart Rate outside the Practice. Adults, N=30. NRCT, acute changes Before-During-After TM compared to autogenic training and relaxation groups. This paper may not have been included because it was in French, but a long English summary of it is available, reprinted in Collected Papers volume 5, which I have shipped to the authors. c. GARNIER, D.; CAZABAT, A.; THÉBAULT, P.; and GAUGE, P. An experimental study: pulmonary ventilation during the Transcendental Meditation technique applications in preventive medicine. Summary of a paper that appeared in Est-Médicine 4(76): , (Paper # 359 in CP) Lower Oxygen Consumption per Kilo Body Weight during and outside TM Practice. Adults, N=20, NRCT, acute changes Before-During-After TM compared to eyes-closed rest in the control group. Not cited. Other relevant papers not cited Wilson, A.F., R.W. Honsberger, J.T. Chiu and H.S. Novey, Transcendental Meditation and asthma. Respiration, : p Page 11

12 Badawi, K., R.K. Wallace, D. Orme-Johnson and A.-M. Rouzeré, Electrophysiologic characteristics of respiratory suspension periods occurring during the practice of the Transcendental Meditation program. Psychosomatic Medicine, (3): p Kesterson, J. and N. Clinch, Metabolic rate, respiratory exchange ratio and apneas during meditation. American Physiological Society, : p. R632-R638. VI.C. Peripheral nerve tests such as skin conductance Outcome Measure: Skin resistance/conductance STUDY SELECTION 1. Studies Incorrectly Excluded Data in these studies should allow performance of a meta-analysis. ORME-JOHNSON, D. W. Autonomic stability and Transcendental Meditation. Psychosomatic Medicine 35: , (Paper #25 in Collected Papers) Design of Exp. 2 NRCT; outcome: spontaneous SR changes before, during and after a TM session, compared to before, during and after a resting session in non-meditating controls; N= 30, age=24-28 yrs; duration 3 weeks BERKER, E. Stability of skin resistance responses one week after instruction in the Transcendental Meditation technique. Department of Biology, Rollins College, Winter Park, Florida, U.S.A., (Paper #27 in Collected Papers) Design: NRCT study on short term effects (Exp 1); N=49, age: yrs, intervention period one week; Outcomes: spontaneous skin resistance responses (SSRR) and trials to habituation Alexander, C. N., Swanson, G. C., Rainforth, M. V., Carlisle, T. W., Todd, C. C., & Oates, R. M. (1993). Effects of the Transcendental Meditation program on stress reduction, health, and employee development: A prospective study in two occupational settings. Anxiety, Stress and Coping: An International Journal, 6, VI.D. Blood gas measurements These three papers are suitable for a meta-analysis on Oxygen consumption WILSON, A. F.; JEVNING, R.; and GUICH, S. Marked reduction of forearm carbon dioxide production during states of decreased metabolism. Physiology and Behavior 41: , (Paper #361 in CP) Reduced Difference between Arterial and Venous CO2 Content in Forearm Metabolism. Adults, N=62. NRCT, acute changes Before-During-After TM compared to unstylized rest in the control group. This paper was cited in the larger Included Studies list but was not included in Chapter 3 review of the physiological effects of meditation. Dhanaraj VH, Singh M. Reduction in metabolic rate during the practice of the Transcendental Meditation technique. Sci Res Maharishi's Transcendental Meditation TM-Sidhi Programme - Collected Papers, 1977; 1:137-9 Design: BA w control group (before TM or EC rest and after 15 min TM or EC rest), N=21, Age=not specified-college undergraduates, Outcomes: O2 consumption, RQ GARNIER, D.; CAZABAT, A.; THÉBAULT, P.; and GAUGE, P. An experimental study: pulmonary ventilation during the Transcendental Meditation technique applications in preventive medicine. Summary of a paper that appeared in Est- Médicine 4(76): , (paper 359 in CP) Lower Oxygen Consumption per Kilo Body Weight during and outside TM Practice. Adults, N=20, BA Design, acute changes Before-During-After TM compared to eyes-closed rest in the control group. Page 12

13 VI.E. Adrenocortical functioning Cortisol levels (pp ) 1) Studies incorrectly excluded Jevning, R., Wilson, A.F., Smith, W.R. (1978). The Transcendental Meditation technique, adrenocortical activity, and implications for stress. Experientia, 34, (Paper #191 in Collected Papers) Compares the acute fall of plasma cortisol during a practice session of the TM technique in a TM group (n=15) with change in the same measure in controls (n=15) after ordinary relaxation. Bevan, A. (1980). Endocrine changes in Transcendental Meditation. Clinical and Experimental Pharmacology and Physiology, 7, (Paper #200 in Collected Papers) Compares the acute fall of serum cortisol during practice of the TM technique in a TM group (n=15) with change in the same measure in controls (n=9) after ordinary relaxation. Subrahmanyam, S., Porkodi, K. (1980). Neurohumoral correlates of Transcendental Meditation. Journal of Biomedicine, 1: (Paper #202 in Collected Papers) Compares plasma cortisol level in normal subjects before learning the TM technique and after 6 months of practice (n=20) (shown in Table I of paper) New meta-analyses to be performed on cortisol change: The following two analyses appear to conform to the author s guidelines. a. The B & A results (6 months) on plasma cortisol levels from Subrahmanyam and Porkodi (1980, see above) should be combined with the within-group changes (4 months) in either the baseline cortisol or the average plasma cortisol from the RCT of MacLean et al. 281 b. The NRCT results on blood plasma cortisol from Jevning, Wilson, and Smith (see above) should be combined with the serum measures of cortisol from Bevan (see above). (Blood levels of cortisol estimated from plasma and from serum are within the margin of error of the assays and raw data can be combined. However, the Bevan study lacks raw data. Thus a numerical estimate of cortisol change must be obtained from the p and n values combined with knowledge of the normal range, as seen in the Jevning et al., MacLean et al., or Subrahmanyam studies, for example.) 2) Studies incorrectly included Page The meta-analysis shown in Figure 33 is inappropriate because, as noted in the Discussion from the MacLean et al. 281 paper, both accounts are from the same study. One report (MacLean et al. 281 ) examined the blood levels of cortisol and other hormones, while the other (Levitsky 276 ) examined the urinary excretion rates of cortisol, other hormones, and neurotransmitter metabolites. This correction will result in dropping the Levitsky 276 dissertation from the cortisol metaanalyses. 3) Corrections of data extraction (into tables or other description of results) The existing meta-analysis on cortisol changes with the TM technique (pages ) is to be dropped. However, please note that the Levitsky 276 data listed were not correctly extracted. Cortisol was determined in each of three 8-hour urine collection periods on the same day, and data were given separately for each of these periods as well as for the waking hours (periods 2 + 3) and the full 24-hour day (periods ). In addition, the cortisol was assayed using two separate methods of analysis. The first method was considered by Levitsky to be superior because the double-antibody assay is said to be more specific and because the analysis was conducted the shortest time after sample collection. The person performing the metaanalysis on page 164 chose to extract data from the less reliable of the two methods and chose data representing time period 1 (during sleep 10 PM to 6 AM) for the TM group and time period 2 (6 AM to 2 PM) for the control group. This comparison is inappropriate because cortisol excretion has a striking circadian rhythm, and for these two periods of the day it tends to differ by large amounts. Page 13

14 4) Corrections for Conclusions/Discussion The conclusion of heterogeneity of results was also incorrect. Note that among the five comparisons of the urinary data from the assay method of choice, the TM group showed significant within group reductions in all but the period 1 (overnight) sample, while the control group showed no significant within group change for any period. Although no between group difference reached significance, the TM versus control changes in cortisol between the pretest and the 4- month posttest were similar for the blood samples of MacLean et al. and the waking and 24-hour urine samples of Levitsky. VI.F. Lipoprotein levels Outcome measure: Total Cholesterol, LDL, HDL STUDY SELECTION 1. Studies Incorrectly Excluded (p , Fig 30) Subrahmanyam, S. and D. Porkodi, Neurohumoral correlates of Transcendental Meditation. Journal of Biomedicine, : p (Paper # 202 in Collected Papers) Design: Before and After TM (no control group); N=40, duration 6 mos; secondary outcome: total cholesterol Castillo-Richmond, A, Schneider RH, Alexander CN, Cook R, Myers H, Nidich SI, Haney C, Rainforth M, & Salerno JW Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans, Stroke 2000, 31, p Design: RCT, N=60, Age: ave 53 yrs; intervention period 6-9 mo, se secondary outcome: total cholesterol, HDL, LDL 2. Cholesterol studies to be excluded from this meta-analysis As recommended for Topic III, it is preferable to separate multimodality interventions from unimodality ones. The following study involved a multimodality intervention: Fields et al., 2002 American Journal of Cardiology (REF# 274 in the report). The following study was correctly excluded from this analysis. The first author, Dr. Cooper, has confirmed by communication with this reviewer that it represents a subgroup analysis of the included study. Cooper, M.J. and M.M. Aygen, A relaxation technique in the management of hypercholesterolemia. Journal of Human Stress, (4): p (Paper # 236 in Collected Papers) VI.G. EMG 1. Studies Incorrectly Excluded: Acute effects of TM compared to relaxation (3 studies) a. Chenard J-R. A controlled study of the influence of Transcendental Meditation on a specific value of the H-reflex (Hoffman reflex) recruitment curve and the surface EMG. Sc Res on Maharishi s Transcendental Meditation and TM-Sidhi program: 3; NRCT, Comparing before, during, and after 20 minutes of TM and relaxation, N=20, Age=19-56, Measures= EMG and H-reflex. b. Sultan SE. A study of the ability of individuals trained in Transcendental Meditation to achieve and maintain levels of physiological relaxation. Sc Res on Maharishi s Transcendental Meditation and TM-Sidhi program: 2; NRCT, Comparing TM and relaxing controls during meditation/relaxation and during task, N=30, Age 22-26, Measures=EMG. Page 14

15 VI.H. AHRQ Report on Meditation Techniques Walton Review Carbohydrate metabolism (e.g. glucose and insulin levels) JEVNING, R.; WILSON, A. F.; PIRKLE, H.; GUICH, S.; and WALSH, R. N. Modulation of red cell metabolism by states of decreased activation: comparison between states. Physiology and Behavior 35: , (paper 362 of CP) Marked Decline of Red Cell Metabolism. Adults, N=52, NRCT, longitudinal changes during unstylized rest before learning TM to changes during TM after 2 weeks if practicing it, as compared to changes in long-term meditators measured during the same periods. This paper was cited in the larger Included Studies list but was not included in Chapter 3 review of the physiological effects of meditation. VI.I. Brain electrophysiology (EEG etc.) VI.I.1. MAJOR COMPULSORY REVISION: The studies listed below in this review section should be included in the topic of EEG Coherence. These studies include. 1. Prospective study on changes in EEG coherence during TM compared to resting controls. a) Dillbeck, M. C. and E. C. Bronson (1981). Short-Term Longitudinal Effects of the Transcendental Meditation Technique on EEG Power and Coherence. The International Journal of Neuroscience. 14(3-4). (Paper #217 from Collected Papers Vol. 3). NRCT, N=15, Mean Age=22.4, Measures=EEG coherence and power. Subjects were randomly assigned to either practice general relaxation or NT for two-weeks, then all subjects learned TM and were measured for change over two weeks of TM practice. b) Gaylord, C.; Orme-Johnson, D.; Willbanks, M.; Travis, F.; Rainforth, M.; and Reynolds, B. The effects of the Transcendental Meditation program on self-concept and EEG coherence in black college students. Abstract of paper presented at the 101st session of the Iowa Academy of Science, Storm Lake, Iowa, April Also see abstract insert in Journal of the Iowa Academy of Science 96(1), A31 A32. Reprinted in the Sc Res on Maharishi s Transcendental Meditation and TM-Sidhi program--collected papers: 5; (Paper # 371, Collected Papers Vol. 5). RCT, N=50, Adults, 2.5 month intervention comparing TM, Progressive Muscle Relaxation, and resting control groups. Measures= EEG coherence and self-concept. Results: Increased EEG coherence during TM from eyes closed compared to no increase in NT or PMR. Longitudinal increase in EEG coherence outside of meditation. c) TRAVIS, F. (2002). Development Along an Integration Scale: Longitudinal Transformation in Brain Dynamics with Regular Transcendental Meditation Practice. Psychophysiology. 39: S81. NRCT Six-month longitudinal changes in frontal coherence, alpha/beta ratios and CNV patterns in 12 TM and 12 ageand gender-matched non-tm subjects. Results: increased frontal coherence, increased alpha/beta ratios, and higher simple CNV and lower choice CNV in the TM group. 2. Acute effects of TM on EEG coherence compared to NT and PMR (2 studies). These studies show that the state of awareness experienced during TM differs from that experienced during eyes-closed rest and PR. a). Gaylord, C., D. Orme-Johnson and F. Travis (1989). The Effects of the Transcendental Mediation Technique and Progressive Muscle Relaxation on EEG Coherence, Stress Reactivity, and Mental Health in Black Adults. The International journal of neuroscience. 46(1-2): Paper # 370, Collected Papers, Vol. 5). RCT, N=83, Adults. One year intervention comparing changes in TM, Progressive Relaxation, and NT. Measures=EEG coherence, mental health factor, cognitive/iq factor. Results: Increased global EEG coherence (all coherence pairs and all Page 15

16 frequencies) during TM compared to eyes closed resting, with no increases during PR or NT. The strongest change during TM compared eyes closed was in the right hemisphere and theta, alpha1 and alpha2. Note: Cited in Included list and in Chapter 3, but not found in the results anywhere. b). Gaylord, C.; Orme-Johnson, D.; Willbanks, M.; Travis, F.; Rainforth, M.; and Reynolds, B. The effects of the Transcendental Meditation program on self-concept and EEG coherence in black college students. Abstract of paper presented at the 101st session of the Iowa Academy of Science, Storm Lake, Iowa, April Also see abstract insert in Journal of the Iowa Academy of Science 96(1), A31 A32. Reprinted in the Sc Res on Maharishi s Transcendental Meditation and TM-Sidhi program (Paper #371, Collected papers: 5; 3025). RCT, N=50, Adults, 2.5 month intervention comparing TM, Progressive Muscle Relaxation, and resting control groups. Measures= EEG coherence and self-concept. Results: Increased EEG coherence during TM from eyes closed compared to no increase in NT or PMR. Longitudinal increase in EEG coherence outside of meditation. Note: Not cited in the AHRQ report. VI.J. Metabolic product levels (e.g. lactic acid) This meta-analysis has papers on lactic acid that can be analyzed. DILLBECK, M. C., and ORME-JOHNSON, D. W. Physiological differences between Transcendental Meditation and rest. American Psychologist 42: , Higher Basal Skin Resistance; Lower Respiration Rate; Lower Plasma Lactate. Lower Baseline Levels of Spontaneous Skin Resistance Responses, Respiration Rate, Heart Rate, and Plasma Lactate. (paper 356 in CP) Adults, Meta-Analysis of 32 Studies Jevning, R., A.F. Wilson, J.P. O'Halloran and R.N. Walsh, Forearm blood flow and metabolism during stylized and unstylized states of decreased activation. American Journal of Physiology, : p. R110-R116. Jevning, R., A.F. Wilson, H. Pirkle, J.P. O'Halloran and R.N. Walsh, Metabolic control in a state of decreased activation: Modulation of red cell metabolism. American Journal of Physiology: Cellular Physiology, (14): p. C457 C461. VII. CHAPTER 3. TOPIC V: EVIDENCE ON THE COGNITIVE/NEUROPSYCHOLOGICAL EFFECTS OF MEDITATION Study Selection VII.A.1. VII.A.2. OVERALL CRITIQUE: a).this section reports on ten commonly reported cognitive/neuropsychological outcomes (pg. 153): 1)attention, 2) memory, 3) perception, 4) other cognitive measures such as cognitive functioning, 5) reasoning, 6) sensorimotor functioning, 7) language, 8) creativity, 9) intelligence, and 10) spatial abilities. b). It neglects to report on other important health-related outcome areas, e.g., mental health e.g., anxiety and depression, which are major contributing factors to the onset and progression of major diseases such as cardiovascular disease. c.) It does not report on important research with children. COMMENT: a). A substantial number of cognitive/neuropsychological studies on Transcendental Meditation were not included in this section. Sections #1 to #10 below list the cognitive/neuropsychological studies that were erroneously excluded from topic V. b.) Important measurable data for health-related outcomes (Table 3: Outcomes of Interest, pg. 19) such as anxiety and depression should be reported to provide a more complete understanding of the effects of meditation. For example, a meta-analysis on anxiety a psychosocial stress risk factor for CVD analyzed over Page 16