Internet-based cognitive behavioral therapy for patients with chronic somatic conditions: a meta-analytic review

Sylvia van Beugen, Maaike Ferwerda, Dane Hoeve, Maroeska M Rovers, Saskia Spillekom-van Koulil, Henriët van Middendorp, Andrea Wm Evers, Sylvia van Beugen, Maaike Ferwerda, Dane Hoeve, Maroeska M Rovers, Saskia Spillekom-van Koulil, Henriët van Middendorp, Andrea Wm Evers

Abstract

Background: Patients with chronic somatic conditions face unique challenges accessing mental health care outside of their homes due to symptoms and physical limitations. Internet-based cognitive behavioral therapy (ICBT) has shown to be effective for various psychological conditions. The increasing number of recent trials need to be systematically evaluated and quantitatively analyzed to determine whether ICBT is also effective for chronic somatic conditions and to gain insight into the types of problems that could be targeted.

Objective: Our goal was to describe and evaluate the effectiveness of guided ICBT interventions for chronic somatic conditions on general psychological outcomes, disease-related physical outcomes, and disease-related impact on daily life outcomes. The role of treatment length was also examined.

Methods: PubMed, PsycINFO, and Embase were searched from inception until February 2012, by combining search terms indicative of effect studies, Internet, and cognitive behavioral therapy. Studies were included if they fulfilled the following six criteria: (1) randomized controlled trial, (2) Internet-based interventions, (3) based on cognitive behavioral therapy, (4) therapist-guided, (5) adult (≥18 years old) patients with an existing chronic somatic condition, and (6) published in English. 23 randomized controlled trials of guided ICBT were selected by 2 independent raters after reviewing 4848 abstracts. Demographic, clinical, and methodological variables were extracted. Standardized mean differences were calculated between intervention and control conditions for each outcome and pooled using random effects models when appropriate.

Results: Guided ICBT was shown to improve all outcome categories with small effect sizes for generic psychological outcomes (effect size range 0.17-0.21) and occasionally larger effects for disease-specific physical outcomes (effect size range 0.07 to 1.19) and disease-related impact outcomes (effect size range 0.17-1.11). Interventions with a longer treatment duration (>6 weeks) led to more consistent effects on depression.

Conclusions: Guided ICBT appears to be a promising and effective treatment for chronic somatic conditions to improve psychological and physical functioning and disease-related impact. The most consistent improvements were found for disease-specific outcomes, which supports the possible relevance of tailoring interventions to specific patient groups. Explorative analyses revealed that longer treatment length holds the promise of larger treatment effects for the specific outcome of depression. While the current meta-analysis focused on several chronic somatic conditions, future meta-analyses for separate chronic somatic conditions can further consolidate these results, also in terms of cost-effectiveness.

Keywords: cognitive behavior therapy; eHealth; internet; intervention; meta-analysis; self-management.

Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
PRISMA flow diagram of study selection.
Figure 2
Figure 2
Risk of bias graph.
Figure 3
Figure 3
Risk of bias summary: review authors' judgements for each included study about each risk of bias item. A=Random sequence generation (selection bias); B=Allocation concealment (selection bias); C=Blinding of participants and personnel (performance bias); D=Blinding of outcome assessment (detection bias); E=Incomplete outcome data (attrition bias); F=Selective reporting (reporting bias).
Figure 4
Figure 4
Forest plot of standardized mean differences of the effect on depression of Internet-based cognitive behavioral therapy compared with a passive control condition.
Figure 5
Figure 5
Forest plot of standardized mean differences of the effect on anxiety of Internet-based cognitive behavioral therapy compared with a passive control condition.
Figure 6
Figure 6
Forest plot of standardized mean differences of the effect on general distress of Internet-based cognitive behavioral therapy compared with a passive control condition.
Figure 7
Figure 7
Forest plot of standardized mean differences of the effect on disease-specific quality of life of Internet-based cognitive behavioral therapy compared with a passive control condition.
Figure 8
Figure 8
Forest plot of standardized mean differences of the effect on disease-specific distress of Internet-based cognitive behavioral therapy compared with a passive control condition.

References

    1. Butler AC, Chapman JE, Forman EM, Beck AT. The empirical status of cognitive-behavioral therapy: a review of meta-analyses. Clin Psychol Rev. 2006 Jan;26(1):17–31. doi: 10.1016/j.cpr.2005.07.003.
    1. Holroyd KA, Nash JM, Pingel JD, Cordingley GE, Jerome A. A comparison of pharmacological (amitriptyline HCL) and nonpharmacological (cognitive-behavioral) therapies for chronic tension headaches. J Consult Clin Psychol. 1991 Jun;59(3):387–93.
    1. Ismail K, Winkley K, Rabe-Hesketh S. Systematic review and meta-analysis of randomised controlled trials of psychological interventions to improve glycaemic control in patients with type 2 diabetes. Lancet. 2004 May 15;363(9421):1589–97. doi: 10.1016/S0140-6736(04)16202-8.
    1. Lee YH, Chiou PY, Chang PH, Hayter M. A systematic review of the effectiveness of problem solving approaches towards symptom management in cancer care. J Clin Nurs. 2011 Jan;20(1-2):73–85. doi: 10.1111/j.1365-2702.2010.03401.x.
    1. Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database Syst Rev. 2008;(3):CD001027. doi: 10.1002/14651858.CD001027.pub2.
    1. Halford J, Brown T. Cognitive-behavioural therapy as an adjunctive treatment in chronic physical illness. Advances in Psychiatric Treatment. 2009 Jun 30;15(4):306–317. doi: 10.1192/apt.bp.107.003731.
    1. White CA. Cognitive behavioral principles in managing chronic disease. West J Med. 2001;175(5):338–42.
    1. Andersson G, Cuijpers P. Pros and cons of online cognitive-behavioural therapy. Br J Psychiatry. 2008;193(4):270–271. doi: 10.1192/bjp.bp.108.054080.
    1. Griffiths F, Lindenmeyer A, Powell J, Lowe P, Thorogood M. Why are health care interventions delivered over the internet? A systematic review of the published literature. J Med Internet Res. 2006;8(2):e10. doi: 10.2196/jmir.8.2.e10.
    1. Andersson E, Ljótsson B, Smit F, Paxling B, Hedman E, Lindefors N, Andersson G, Rück C. Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial. BMC Public Health. 2011;11:215. doi: 10.1186/1471-2458-11-215.
    1. Tate DF, Finkelstein EA, Khavjou O, Gustafson A. Cost effectiveness of internet interventions: review and recommendations. Ann Behav Med. 2009;38(1):40–45. doi: 10.1007/s12160-009-9131-6.
    1. van Os-Medendorp H, Koffijberg H, Eland-de Kok PC, van der Zalm A, de Bruin-Weller MS, Pasmans SG, Ros WJ, Thio HB, Knol MJ, Bruijnzeel-Koomen CA. E-health in caring for patients with atopic dermatitis: a randomized controlled cost-effectiveness study of internet-guided monitoring and online self-management training. Br J Dermatol. 2012;166(5):1060–8. doi: 10.1111/j.1365-2133.2012.10829.x.
    1. Hedman E, Ljótsson B, Lindefors N. Cognitive behavior therapy via the Internet: a systematic review of applications, clinical efficacy and cost-effectiveness. Expert Rev Pharmacoecon Outcomes Res. 2012 Dec;12(6):745–64. doi: 10.1586/erp.12.67.
    1. Barak A, Hen L, Boniel-Nissim M, Shapira N. A Comprehensive Review and a Meta-Analysis of the Effectiveness of Internet-Based Psychotherapeutic Interventions. Journal of Technology in Human Services. 2008 Jul 03;26(2-4):109–160. doi: 10.1080/15228830802094429.
    1. Griffiths F, Lindenmeyer A, Powell J, Lowe P, Thorogood M. Why are health care interventions delivered over the internet? A systematic review of the published literature. J Med Internet Res. 2006;8(2):e10. doi: 10.2196/jmir.8.2.e10.
    1. Spek V, Cuijpers P, Nyklícek I, Riper H, Keyzer J, Pop V. Internet-based cognitive behaviour therapy for symptoms of depression and anxiety: a meta-analysis. Psychol Med. 2007 Mar;37(3):319–28. doi: 10.1017/S0033291706008944.
    1. Andersson G, Ljótsson B, Weise C. Internet-delivered treatment to promote health. Curr Opin Psychiatry. 2011 Mar;24(2):168–72. doi: 10.1097/YCO.0b013e3283438028.
    1. Cuijpers P, van Straten A, Andersson G. Internet-administered cognitive behavior therapy for health problems: a systematic review. J Behav Med. 2008 Apr;31(2):169–77. doi: 10.1007/s10865-007-9144-1.
    1. Eland-de Kok P, van Os-Medendorp H, Vergouwe-Meijer A, Bruijnzeel-Koomen C, Ros W. A systematic review of the effects of e-health on chronically ill patients. J Clin Nurs. 2011 Nov;20(21-22):2997–3010. doi: 10.1111/j.1365-2702.2011.03743.x.
    1. Macea DD, Gajos K, Daglia Calil YA, Fregni F. The efficacy of Web-based cognitive behavioral interventions for chronic pain: a systematic review and meta-analysis. J Pain. 2010 Oct;11(10):917–29. doi: 10.1016/j.jpain.2010.06.005.
    1. Stinson J, Wilson R, Gill N, Yamada J, Holt J. A systematic review of internet-based self-management interventions for youth with health conditions. J Pediatr Psychol. 2009 Jun;34(5):495–510. doi: 10.1093/jpepsy/jsn115.
    1. Wantland DJ, Portillo CJ, Holzemer WL, Slaughter R, McGhee EM. The effectiveness of Web-based vs. non-Web-based interventions: a meta-analysis of behavioral change outcomes. J Med Internet Res. 2004 Nov 10;6(4):e40. doi: 10.2196/jmir.6.4.e40.
    1. Webb TL, Joseph J, Yardley L, Michie S. Using the internet to promote health behavior change: a systematic review and meta-analysis of the impact of theoretical basis, use of behavior change techniques, and mode of delivery on efficacy. J Med Internet Res. 2010;12(1):e4. doi: 10.2196/jmir.1376.
    1. Bouman T, Schaap C. Cognities: wat moet ik hiervan denken? In: Sanderman R, Pool G, editors. Handboek psychologische interventies bij chronisch-somatische aandoeningen. Assen: Van Gorcum; 2004. pp. 143–152.
    1. Christensen H, Griffiths KM, Mackinnon AJ, Brittliffe K. Online randomized controlled trial of brief and full cognitive behaviour therapy for depression. Psychol Med. 2006;36(12):1737–46. doi: 10.1017/S0033291706008695.
    1. Anderson G. Chronic care: making the case for ongoing care. Princeton, NJ: Robert Wood Johnson Foundation; 2010. [2014-03-12]. .
    1. Beck AT, Rush AJ, Shaw BF, Emery G. Cognitive therapy of depression. New York: Guilford Press; 1979.
    1. Dori GA, Overholser JC. Evaluating depression severity and remission with a modified Beck Depression Inventory. Personality and Individual Differences. 2000 Jun;28(6):1045–1061. doi: 10.1016/S0191-8869(99)00156-7.
    1. Cochrane Collaboration Cochrane handbook for systematic reviews of interventions version 5.1. 2011. [2014-03-12].
    1. Fisher LD, Dixon DO, Herson J, Frankowski RK, Hearron MS, Peace KE. Intention to treat in clinical trials. In: Peace KE, editor. Statistical issues in drug research and development. New York: M. Dekker; 1990. pp. 331–350.
    1. Morris SB. Estimating effect sizes from pretest-posttest-control group designs. Organizational Research Methods. 2007 Jul 23;11(2):364–386. doi: 10.1177/1094428106291059.
    1. Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, NJ: L. Erlbaum Associates; 1988.
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. doi: 10.1136/bmj.327.7414.557.
    1. Hedges LV, Vevea JL. Fixed- and random-effects models in meta-analysis. Psychological Methods. 1998;3(4):486–504. doi: 10.1037/1082-989X.3.4.486.
    1. Abbott JA, Kaldo V, Klein B, Austin D, Hamilton C, Piterman L, Williams B, Andersson G. A cluster randomised trial of an internet-based intervention program for tinnitus distress in an industrial setting. Cogn Behav Ther. 2009;38(3):162–73. doi: 10.1080/16506070902763174.
    1. Andersson G, Lundström P, Ström L. Internet-based treatment of headache: does telephone contact add anything? Headache. 2003 Apr;43(4):353–61.
    1. Andersson G, Strömgren T, Ström L, Lyttkens L. Randomized controlled trial of internet-based cognitive behavior therapy for distress associated with tinnitus. Psychosom Med. 2002;64(5):810–6.
    1. Berman RL, Iris MA, Bode R, Drengenberg C. The effectiveness of an online mind-body intervention for older adults with chronic pain. J Pain. 2009 Jan;10(1):68–79. doi: 10.1016/j.jpain.2008.07.006.
    1. Brattberg G. Internet-based rehabilitation for individuals with chronic pain and burnout: a randomized trial. Int J Rehabil Res. 2006 Sep;29(3):221–7. doi: 10.1097/01.mrr.0000210055.17291.f5.
    1. Buhrman M, Fältenhag S, Ström L, Andersson G. Controlled trial of Internet-based treatment with telephone support for chronic back pain. Pain. 2004 Oct;111(3):368–77. doi: 10.1016/j.pain.2004.07.021.
    1. Buhrman M, Nilsson-Ihrfeldt E, Jannert M, Ström L, Andersson G. Guided internet-based cognitive behavioural treatment for chronic back pain reduces pain catastrophizing: a randomized controlled trial. J Rehabil Med. 2011 May;43(6):500–5. doi: 10.2340/16501977-0805.
    1. David N, Schlenker P, Prudlo U, Larbig W. Online counseling via e-mail for breast cancer patients on the German internet: preliminary results of a psychoeducational intervention. Psychosoc Med. 2011;8:Doc05. doi: 10.3205/psm000074.
    1. Devineni T, Blanchard EB. A randomized controlled trial of an internet-based treatment for chronic headache. Behav Res Ther. 2005 Mar;43(3):277–92. doi: 10.1016/j.brat.2004.01.008.
    1. Ghahari S, Leigh Packer T, Passmore AE. Effectiveness of an online fatigue self-management programme for people with chronic neurological conditions: a randomized controlled trial. Clin Rehabil. 2010 Aug;24(8):727–44. doi: 10.1177/0269215509360648.
    1. Hedborg K, Muhr C. Multimodal behavioral treatment of migraine: an Internet-administered, randomized, controlled trial. Ups J Med Sci. 2011 Aug;116(3):169–86. doi: 10.3109/03009734.2011.575963.
    1. Hesser H, Gustafsson T, Lundén C, Henrikson O, Fattahi K, Johnsson E, Zetterqvist Westin V, Carlbring P, Mäki-Torkko E, Kaldo V, Andersson G. A randomized controlled trial of Internet-delivered cognitive behavior therapy and acceptance and commitment therapy in the treatment of tinnitus. J Consult Clin Psychol. 2012 Aug;80(4):649–61. doi: 10.1037/a0027021.
    1. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 Sep;47(9):797–802. doi: 10.1016/j.brat.2009.05.002.
    1. Kaldo V, Levin S, Widarsson J, Buhrman M, Larsen HC, Andersson G. Internet versus group cognitive-behavioral treatment of distress associated with tinnitus: a randomized controlled trial. Behav Ther. 2008 Dec;39(4):348–59. doi: 10.1016/j.beth.2007.10.003.
    1. Ljótsson B, Andersson G, Andersson E, Hedman E, Lindfors P, Andréewitch S, Rück C, Lindefors N. Acceptability, effectiveness, and cost-effectiveness of internet-based exposure treatment for irritable bowel syndrome in a clinical sample: a randomized controlled trial. BMC Gastroenterol. 2011;11:110. doi: 10.1186/1471-230X-11-110.
    1. Ljótsson B, Hedman E, Lindfors P, Hursti T, Lindefors N, Andersson G, Rück C. Long-term follow-up of internet-delivered exposure and mindfulness based treatment for irritable bowel syndrome. Behav Res Ther. 2011;49(1):58–61. doi: 10.1016/j.brat.2010.10.006.
    1. Ljótsson B, Hedman E, Andersson E, Hesser H, Lindfors P, Hursti T, Rydh S, Rück C, Lindefors N, Andersson G. Internet-delivered exposure-based treatment vs. stress management for irritable bowel syndrome: a randomized trial. Am J Gastroenterol. 2011;106(8):1481–91. doi: 10.1038/ajg.2011.139.
    1. Lorig K, Ritter PL, Laurent DD, Plant K, Green M, Jernigan VB, Case S. Online diabetes self-management program: a randomized study. Diabetes Care. 2010;33(6):1275–81. doi: 10.2337/dc09-2153.
    1. Lorig KR, Ritter PL, Laurent DD, Plant K. Internet-based chronic disease self-management: a randomized trial. Med Care. 2006;44(11):964–71. doi: 10.1097/01.mlr.0000233678.80203.c1.
    1. Lorig KR, Ritter PL, Laurent DD, Plant K. The internet-based arthritis self-management program: a one-year randomized trial for patients with arthritis or fibromyalgia. Arthritis Rheum. 2008 Jul 15;59(7):1009–17. doi: 10.1002/art.23817.
    1. Ström L, Pettersson R, Andersson G. A controlled trial of self-help treatment of recurrent headache conducted via the Internet. J Consult Clin Psychol. 2000 Aug;68(4):722–7.
    1. Thompson NJ, Walker ER, Obolensky N, Winning A, Barmon C, Diiorio C, Compton MT. Distance delivery of mindfulness-based cognitive therapy for depression: project UPLIFT. Epilepsy Behav. 2010 Nov;19(3):247–54. doi: 10.1016/j.yebeh.2010.07.031.
    1. van Bastelaar KM, Pouwer F, Cuijpers P, Riper H, Snoek FJ. Web-based depression treatment for type 1 and type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2011 Feb;34(2):320–5. doi: 10.2337/dc10-1248.
    1. Siddiqui O, Ali MW. A comparison of the random-effects pattern mixture model with last-observation-carried-forward (LOCF) analysis in longitudinal clinical trials with dropouts. J Biopharm Stat. 1998 Nov;8(4):545–63. doi: 10.1080/10543409808835259.
    1. Verbeke G, Molenberghs G. Linear Mixed Models for Longitudinal Data (Springer Series in Statistics) New York: Springer; 2000.
    1. Li X, Mehrotra DV, Barnard J. Analysis of incomplete longitudinal binary data using multiple imputation. Stat Med. 2006 Jun 30;25(12):2107–24. doi: 10.1002/sim.2343.
    1. Beck R, Fernandez E. Cognitive-behavioral therapy in the treatment of anger: a meta-analysis. Cog Ther Res. 1990;22:63–74. doi: 10.1023/A:1018763902991.
    1. Patrick DL, Deyo RA. Generic and disease-specific measures in assessing health status and quality of life. Med Care. 1989 Mar;27(3 Suppl):S217–32.
    1. Wiebe S, Guyatt G, Weaver B, Matijevic S, Sidwell C. Comparative responsiveness of generic and specific quality-of-life instruments. J Clin Epidemiol. 2003 Jan;56(1):52–60.
    1. Andersson G, Estling F, Jakobsson E, Cuijpers P, Carlbring P. Can the patient decide which modules to endorse? An open trial of tailored internet treatment of anxiety disorders. Cogn Behav Ther. 2011;40(1):57–64. doi: 10.1080/16506073.2010.529457.
    1. Carlbring P, Maurin L, Törngren C, Linna E, Eriksson T, Sparthan E, Strååt M, Marquez von Hage C, Bergman-Nordgren L, Andersson G. Individually-tailored, Internet-based treatment for anxiety disorders: A randomized controlled trial. Behav Res Ther. 2011 Jan;49(1):18–24. doi: 10.1016/j.brat.2010.10.002.
    1. Lustria ML, Cortese J, Noar SM, Glueckauf RL. Computer-tailored health interventions delivered over the Web: review and analysis of key components. Patient Educ Couns. 2009 Feb;74(2):156–73. doi: 10.1016/j.pec.2008.08.023.
    1. Morrison LG, Yardley L, Powell J, Michie S. What design features are used in effective e-health interventions? A review using techniques from Critical Interpretive Synthesis. Telemed J E Health. 2012 Mar;18(2):137–44. doi: 10.1089/tmj.2011.0062.
    1. Beltman MW, Voshaar RC, Speckens AE. Cognitive-behavioural therapy for depression in people with a somatic disease: meta-analysis of randomised controlled trials. Br J Psychiatry. 2010 Jul;197(1):11–9. doi: 10.1192/bjp.bp.109.064675.
    1. Hesser H, Weise C, Westin VZ, Andersson G. A systematic review and meta-analysis of randomized controlled trials of cognitive-behavioral therapy for tinnitus distress. Clin Psychol Rev. 2011 Jun;31(4):545–53. doi: 10.1016/j.cpr.2010.12.006.
    1. Hoffman BM, Papas RK, Chatkoff DK, Kerns RD. Meta-analysis of psychological interventions for chronic low back pain. Health Psychol. 2007;26(1):1–9. doi: 10.1037/0278-6133.26.1.1.
    1. Boutron I, Tubach F, Giraudeau B, Ravaud P. Blinding was judged more difficult to achieve and maintain in nonpharmacologic than pharmacologic trials. J Clin Epidemiol. 2004;57(6):543–50. doi: 10.1016/j.jclinepi.2003.12.010.
    1. Eysenbach G, CONSORT-EHEALTH Group CONSORT-EHEALTH: improving and standardizing evaluation reports of Web-based and mobile health interventions. J Med Internet Res. 2011;13(4):e126. doi: 10.2196/jmir.1923.
    1. Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol. 1992 Mar;45(3):255–65.
    1. Naylor CD. Two cheers for meta-analysis: problems and opportunities in aggregating results of clinical trials. CMAJ. 1988;138(10):891–5.
    1. Eysenbach G. The law of attrition. J Med Internet Res. 2005;7(1):e11. doi: 10.2196/jmir.7.1.e11.
    1. McAuley L, Pham B, Tugwell P, Moher D. Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses? Lancet. 2000 Oct 7;356(9237):1228–31. doi: 10.1016/S0140-6736(00)02786-0.
    1. Couper MP, Alexander GL, Zhang N, Little RJ, Maddy N, Nowak MA, McClure JB, Calvi JJ, Rolnick SJ, Stopponi MA, Cole Johnson C. Engagement and retention: measuring breadth and depth of participant use of an online intervention. J Med Internet Res. 2010;12(4):e52. doi: 10.2196/jmir.1430.
    1. Morrison LG, Yardley L, Powell J, Michie S. What design features are used in effective e-health interventions? A review using techniques from Critical Interpretive Synthesis. Telemed J E Health. 2012 Mar;18(2):137–44. doi: 10.1089/tmj.2011.0062.
    1. Schubart JR, Stuckey HL, Ganeshamoorthy A, Sciamanna CN. Chronic health conditions and internet behavioral interventions: a review of factors to enhance user engagement. Comput Inform Nurs. 2011 Feb;29(2):81–92. doi: 10.1097/NCN.0b013e3182065eed.
    1. Kelders SM, Kok RN, Ossebaard HC, Van Gemert-Pijnen JE. Persuasive system design does matter: a systematic review of adherence to web-based interventions. J Med Internet Res. 2012;14(6):e152. doi: 10.2196/jmir.2104.
    1. Danaher BG, Seeley JR. Methodological issues in research on web-based behavioral interventions. Ann Behav Med. 2009 Aug;38(1):28–39. doi: 10.1007/s12160-009-9129-0.
    1. Sowan AK, Jenkins LS. Paradata: a new data source from web-administered measures. Comput Inform Nurs. 2010;28(6):333–42; quiz 343. doi: 10.1097/NCN.0b013e3181f698fd.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe