|
 |
| STATISTICS |
|
| Year : 2016 | Volume
: 7
| Issue : 3 | Page : 144-146 |
|
Common pitfalls in statistical analysis: Intention-to-treat versus per-protocol analysis
Priya Ranganathan1, CS Pramesh2, Rakesh Aggarwal3
1 Department of Anaesthesiology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
2 Department of Surgical Oncology, Division of Thoracic Surgery, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
3 Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| Date of Web Publication | 28-Jun-2016 |
Correspondence Address:
Priya Ranganathan
Department of Anaesthesiology, Tata Memorial Centre, Ernest Borges Road, Parel, Mumbai - 400 012, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2229-3485.184823
 Abstract | | |
During the conduct of clinical trials, it is not uncommon to have protocol violations or inability to assess outcomes. This article in our series on common pitfalls in statistical analysis explains the complexities of analyzing results from such trials and highlights the importance of "intention-to-treat" analysis. Keywords: Bias, biostatistics, intention-to-treat analysis
How to cite this article:
Ranganathan P, Pramesh C S, Aggarwal R. Common pitfalls in statistical analysis: Intention-to-treat versus per-protocol analysis. Perspect Clin Res 2016;7:144-6 |
How to cite this URL:
Ranganathan P, Pramesh C S, Aggarwal R. Common pitfalls in statistical analysis: Intention-to-treat versus per-protocol analysis. Perspect Clin Res [serial online] 2016 [cited 2020 Oct 30];7:144-6. Available from: https://www.picronline.org/text.asp?2016/7/3/144/184823 |
| Introduction | |  |
In interventional studies, a subset of participants often do not conform to the protocol. These "protocol violations" can be of various types: One or more participants for some reason do not receive the respective interventions to which they were randomized, inadvertently receive an intervention meant for the other trial arm, receive a prohibited concomitant intervention, or are not available for assessment of the planned outcome either because of loss to follow-up or for another reason. [1] During the analysis of the trial results, the researcher is tempted to exclude such "nonconforming" participants. The motivation is not one of deceit, but of integrity, ensuring that comparisons are made between those participants in each trial arm who strictly adhered to the planned treatment so that the true efficacy of one intervention over the other can be assessed.
However, despite the above apparent attractiveness of this approach, such exclusion poses multiple problems. [1] These include:
- It violates the principle of randomization. In a 2-arm study, randomization ensures comparability of the two groups, i.e., balanced for known and unknown confounders or prognostic factors, only as they were originally randomized. When some participants in either or both the groups are excluded, the remaining participants in the two groups can no longer be considered as balanced. The problem becomes larger as the number of exclusions increases
- At times, the noncompliance is related to a particular intervention or to disease severity. For instance, the inability to complete the scheduled treatment or appearance of unacceptable side effects may be more frequent in patients with severe disease. In addition, these may occur more often in the active treatment arm than in the placebo arm. Hence, exclusion of the participants who do not complete the treatment or follow-up as planned would lead to differential exclusion of patients with severe disease in the treated group, with the residual group unlikely to resemble the original group obtained at randomization. This may make the treatment look better than it actually is
- Exclusion of participants in one or both groups, particularly if their number is large, may lead to a significant reduction in sample size and hence in study power
- Exclusions can introduce a bias. Often the decision to exclude a particular participant is controlled, at least to some extent, by the investigator, who may be tempted to exclude patients who are not doing well in a particular arm
- The purpose of a trial is to assess the proportion of persons in a group who may be expected to benefit from a particular treatment. Those who do not complete treatment can of course not be expected to benefit from it. The proportion of responders among those who complete treatment thus provides an exaggerated estimate of treatment effect - this does not accurately reflect the beneficial effect that may be expected in clinical practice among those who are prescribed this particular treatment.
To obviate (or minimize) these problems, it is recommended that "intention-to-treat (ITT) analysis" be used. The principle of ITT analysis is that all participants should be analyzed in the group to which they had been randomized, i.e. as if they had received the intervention which they were supposed to receive, irrespective of the treatment actually received. Fisher defines ITT as analysis which "Includes all randomized patients in the groups to which they were randomly assigned, regardless of their adherence with the entry criteria, regardless of the treatment they actually received, and regardless of subsequent withdrawal from treatment or deviation from the protocol." [2]
The use of ITT analysis ensures maintenance of comparability between groups as obtained through randomization, maintains sample size, and eliminates bias. In addition, results obtained in such analysis more closely represent clinical practice, dealing with "effectiveness" of the intervention rather than "efficacy." In view of these advantages, ITT is today considered as a defacto standard for analysis of clinical trials, though a minority school of thought believes that this approach is too conservative. [1]
In contrast, per-protocol (PP) analysis refers to inclusion in the analysis of only those patients who strictly adhered to the protocol. The PP analysis provides an estimate of the true efficacy of an intervention, i.e., among those who completed the treatment as planned. However, as discussed above, its results do not represent the real life situation and it is likely to show an exaggerated treatment effect.
The CONSORT guidelines for reporting of "parallel group randomized controlled trials" recommend that both ITT and PP analyses should be reported for all planned outcomes to allow readers to interpret the effect of an intervention. [3]
Of course, there are some special situations. For instance, in noninferiority trials, the use of PP analysis is considered particularly important. [4] A detailed discussion of this is beyond the purview of this piece, but will be done in a subsequent article in this series.
A randomized trial published recently in the New England Journal of Medicine compared early (intervention arm) versus delayed (standard arm) introduction of allergenic foods into the diet of breast-fed children. [5] The primary outcome was the development of allergy to any food between 1 and 3 years of age. Results from the ITT analysis (1162 participants) showed no difference between groups for the primary outcome (intervention arm: 32/567 [5.6%] versus standard arm: 42/595 [7.1%]; P = ns). However, a PP analysis (732 participants) showed a significantly lower frequency of food allergy in the intervention arm versus the standard arm (5/208 [2.4%] vs. 38/524 [7.3%]; P = 0.01). It is interesting to note that only 32% (208/652) of the participants in the intervention arm adhered to the protocol as compared to 88% (524/595) of the participants in the standard arm. The authors have offered several explanations for this lack of compliance. Importantly, and in our opinion rightly, they gave precedence to the results of the ITT analysis over those of the PP analysis, and concluded that "the trial did not show the efficacy of early introduction of allergenic foods."
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Gupta SK. Intention-to-treat concept: A review. Perspect Clin Res 2011;2:109-12.  [ PUBMED]  |
| 2. | 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: Marcel Dekker; 1990. p. 331-50. |
| 3. | Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. PLoS Med 2010;7:e1000251. [ PUBMED] |
| 4. | Schumi J, Wittes JT. Through the looking glass: Understanding non-inferiority. Trials 2011;12:106. |
| 5. | Perkin MR, Logan K, Tseng A, Raji B, Ayis S, Peacock J, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med 2016;374:1733-43. |
| This article has been cited by | | 1 |
Cluster randomized controlled trial (RCT) to support parental contact for children in out-of-home care |
|
| Aino Suomi,Nina Lucas,Morag McArthur,Cathy Humphreys,Timothy Dobbins,Stephanie Taplin | | Child Abuse & Neglect. 2020; 109: 104708 | | [Pubmed] | [DOI] | | | 2 |
Study designs: Part 5 – Interventional studies (III) |
|
| Priya Ranganathan,Rakesh Aggarwal | | Perspectives in Clinical Research. 2020; 11(1): 47 | | [Pubmed] | [DOI] | | | 3 |
Ethics and etiquette in an emergency vaccine trial. The orchestration of compliance |
|
| Arsenii Alenichev | | Global Bioethics. 2020; 31(1): 13 | | [Pubmed] | [DOI] | | | 4 |
Are patient educational resources effective at deterring stroke survivors from considering experimental stem cell treatments? A randomized controlled trial |
|
| D.J. Unsworth,J.L. Mathias,D.S. Dorstyn,S.A. Koblar | | Patient Education and Counseling. 2020; | | [Pubmed] | [DOI] | | | 5 |
Effectiveness of LiuZiJue Qigong versus traditional core stability training for poststroke patients complicated with abnormal trunk postural control: study protocol for a single-center randomized controlled trial |
|
| Chen Wang,Long Yu,Jian Yang,Ren Wei Wang,Ya Nan Zheng,Ying Zhang | | Trials. 2020; 21(1) | | [Pubmed] | [DOI] | | | 6 |
Adjuvanted recombinant HBV vaccine (HBV-AS04) is effective over extended follow-up in dialysis population. An open-label non randomized trial |
|
| Fabrizio Fabrizi,Roberta Cerutti,Rebeca Garcia-Agudo,Cecilia Bellincioni,Giulia Porata,Giulia Frontini,Sami Aoufi-Rabih,Piergiorgio Messa | | Clinics and Research in Hepatology and Gastroenterology. 2020; | | [Pubmed] | [DOI] | | | 7 |
Improving Access to Psychological Therapies (IAPT) in the United Kingdom: A systematic review and meta-analysis of 10-years of practice-based evidence |
|
| Sarah Wakefield,Stephen Kellett,Melanie Simmonds-Buckley,Daniel Stockton,Abigail Bradbury,Jaime Delgadillo | | British Journal of Clinical Psychology. 2020; | | [Pubmed] | [DOI] | | | 8 |
Tuberculosis Chemotherapy Outcome in the Littoral Region of Cameroon: A Meta-analysis of Treatment Success Rate between 2014 and 2016 |
|
| Dorgelesse F. Kouemo Motse,Dickson Shey Nsagha,Dieudonné Adiogo,Loick P. Kojom Foko,Pride M. Teyim,Alain Chichom-Mefire,Jules C. Nguedia Assob | | BioMed Research International. 2020; 2020: 1 | | [Pubmed] | [DOI] | | | 9 |
EMDR for children with medically related subthreshold PTSD: short-term effects on PTSD, blood-injection-injury phobia, depression and sleep |
|
| Maya G. Meentken,Malindi van der Mheen,Ingrid M. van Beynum,Elisabeth W. C. Aendekerk,Jeroen S. Legerstee,Jan van der Ende,Riwka Del Canho,Ramón J. L. Lindauer,Manon H. J. Hillegers,Henriette A. Moll,Wim A. Helbing,Elisabeth M. W. J. Utens | | European Journal of Psychotraumatology. 2020; 11(1): 1705598 | | [Pubmed] | [DOI] | | | 10 |
Test Agreement between Roche Cobas 6800 and Cepheid GeneXpert Xpress SARS-CoV-2 Assays at High Cycle Threshold Ranges |
|
| Kari Broder,Ahmed Babiker,Charles Myers,Terri White,Heather Jones,John Cardella,Eileen M. Burd,Charles E. Hill,Colleen S. Kraft,Alexander J. McAdam | | Journal of Clinical Microbiology. 2020; 58(8) | | [Pubmed] | [DOI] | | | 11 |
A study protocol for a cluster randomised controlled trial on mindfulness-based stress reduction: studying effects of mindfulness-based stress reduction and an additional organisational health intervention on mental health and work-related perceptions of teachers in Dutch secondary vocational schools |
|
| Math Janssen,Yvonne Heerkens,Beatrice Van der Heijden,Hubert Korzilius,Pascale Peters,Josephine Engels | | Trials. 2020; 21(1) | | [Pubmed] | [DOI] | | | 12 |
Effects of Predischarge Patient Education Combined With Postdischarge Follow-Ups on Self-Care, Readmission, Sleep, and Depression in Patients With Heart Failure |
|
| Hsing-Mei CHEN,Shan-Tair WANG,Shyh-Jong WU,Chee-Siong LEE,Susan J. FETZER,Liang-Miin TSAI | | Journal of Nursing Research. 2020; 28(5): e112 | | [Pubmed] | [DOI] | | | 13 |
Can self-management programmes change healthcare utilisation in COPD? |
|
| Katelyn R. Smalley,Lisa Aufegger,Kelsey Flott,Erik K. Mayer,Ara Darzi | | Patient Education and Counseling. 2020; | | [Pubmed] | [DOI] | | | 14 |
Effects of Dietary or Supplementary Micronutrients on Sex Hormones and IGF-1 in Middle and Older Age: A Systematic Review and Meta-Analysis |
|
| Ryan Janjuha,Diane Bunn,Richard Hayhoe,Lee Hooper,Asmaa Abdelhamid,Shaan Mahmood,Joseph Hayden-Case,Will Appleyard,Sophie Morris,Ailsa Welch | | Nutrients. 2020; 12(5): 1457 | | [Pubmed] | [DOI] | | | 15 |
Polyphenols intervention is an effective strategy to ameliorate inflammatory bowel disease: a systematic review and meta-analysis |
|
| Fang Liu,Deming Li,Xinjing Wang,Yuan Cui,Xinli Li | | International Journal of Food Sciences and Nutrition. 2020; : 1 | | [Pubmed] | [DOI] | | | 16 |
Computerised cognitive training to improve cognition including delirium following coronary artery bypass grafting surgery: protocol for a blinded randomised controlled trial |
|
| Danielle Greaves,Peter J Psaltis,Amit Lampit,Daniel H J Davis,Ashleigh E Smith,Alice Bourke,Michael G Worthington,Michael J Valenzuela,Hannah A D Keage | | BMJ Open. 2020; 10(2): e034551 | | [Pubmed] | [DOI] | | | 17 |
Addressing Syndemics and Self-care in Individuals with Uncontrolled HIV: An Open Trial of a Transdiagnostic Treatment |
|
| S. A. Safren,A. Harkness,J. S. Lee,B. G. Rogers,N. A. Mendez,J. F. Magidson,A. J. Blashill,S. Bainter,A. Rodriguez,G. Ironson | | AIDS and Behavior. 2020; | | [Pubmed] | [DOI] | | | 18 |
A Randomized Trial of Static and Articulating Spacers for the Treatment of Infection Following Total Knee Arthroplasty |
|
| Cindy R. Nahhas,Peter N. Chalmers,Javad Parvizi,Scott M. Sporer,Keith R. Berend,Mario Moric,Antonia F. Chen,Matthew S. Austin,Gregory K. Deirmengian,Michael J. Morris,Craig J. Della Valle | | The Journal of Bone and Joint Surgery. 2020; 102(9): 778 | | [Pubmed] | [DOI] | | | 19 |
Findings From a Real-World Translation Study of the Evidence-Based “Partners in Dementia Care” |
|
| David M Bass,Thomas Hornick,Mark Kunik,Katherine S Judge,Branka Primetica,Keith Kearney,Julie Rentsch,Catherine Mccarthy,Jennifer Grim,J Jill Suitor | | Innovation in Aging. 2019; 3(3) | | [Pubmed] | [DOI] | | | 20 |
Women in LOVe: Lacto-Ovo-Vegetarian Diet Rich in Omega-3 Improves Vasomotor Symptoms in Postmenopausal Women. An Exploratory Randomized Controlled Trial |
|
| Ornella Rotolo,Iris Zinzi,Nicola Veronese,Anna M. Cisternino,Rosa Reddavide,Rosa Inguaggiato,Gioacchino Leandro,Maria Notarnicola,Valeria Tutino,Valentina De Nunzio,Giampiero De Leonardis,Vito Guerra,Rossella Donghia,Fabio Fucilli,Raffaella Licinio,Anna Mastrosimini,Caterina C.M. Rinaldi,Tiziana Daddabbo,Nicola Giampaolo,Palma A. Iacovazzi,Sara Giannico,Maria G. Caruso | | Endocrine, Metabolic & Immune Disorders - Drug Targets. 2019; 19(8): 1232 | | [Pubmed] | [DOI] | | | 21 |
Methods for the Watch the Spot Trial. A Pragmatic Trial of More- versus Less-Intensive Strategies for Active Surveillance of Small Pulmonary Nodules |
|
| Michael K. Gould,Rebecca Smith-Bindman,Karen Kelly,Danielle E. Altman,Igor Barjaktarevic,Beth Creekmur,Evan de Bie,Debra S. Dyer,Eduardo J. Mortani Barbosa,Richard A. Mularski,Lihong Qi,Laszlo T. Vaszar,Sophronia Yu,Diana L. Miglioretti | | Annals of the American Thoracic Society. 2019; 16(12): 1567 | | [Pubmed] | [DOI] | | | 22 |
Results of a multicentre double-blind placebo-controlled randomized trial of the liquid form of Anaferon for children in the treatment of acute upper respiratory tract infections |
|
| B. M. Blokhin,O. V. Shamsheva,N. L. Chernaya,I. G. Sitnikov,S. G. Lazareva,N. B. Balzerovich,O. A. Perminova,O. V. Zhiglinskaya,M. Yu. Koshavtseva | | Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2019; 64(4): 105 | | [Pubmed] | [DOI] | | | 23 |
Open reduction and plate fixation compared with non-surgical treatment for displaced midshaft clavicle fracture |
|
| Miao Qin,Shishun Zhao,Wenlai Guo,Li Tang,Hangyu Li,Xuejie Wang,Zhe Zhu,Tianwen Sun | | Medicine. 2019; 98(20): e15638 | | [Pubmed] | [DOI] | | | 24 |
*The efficacy of the attachment-based SAFE® prevention program: a randomized control trial including mothers and fathers |
|
| I. Walter,S. Landers,J. Quehenberger,E. Carlson,K. H. Brisch | | Attachment & Human Development. 2019; : 1 | | [Pubmed] | [DOI] | | | 25 |
GRADE-ing the Benefit/Risk Equation in Food Immunotherapy |
|
| Bettina Duca,Nandinee Patel,Paul J. Turner | | Current Allergy and Asthma Reports. 2019; 19(6) | | [Pubmed] | [DOI] | | | 26 |
The CABANA Debate – Once a Treatment Becomes Popular, it is Hard to Interpret the Results in Medicine |
|
| Ozcan Ozeke,Serkan Cay,Firat Ozcan,Serkan Topaloglu,Dursun Aras | | European Journal of Arrhythmia & Electrophysiology. 2019; 5(1): 17 | | [Pubmed] | [DOI] | | | 27 |
Use of a Bidirectional Text Messaging System for Emergency Department Follow-Up Versus Usual Follow-Up |
|
| Brooks J. Obr,Tracy Young,Karisa K. Harland,Andrew Nugent | | Telemedicine and e-Health. 2019; | | [Pubmed] | [DOI] | | | 28 |
Randomized Controlled Trials and Quasi-Experimental Studies Published in Nursing Journals: Findings From a Scoping Review With Implications for Further Research |
|
| Silvia Gonella,Paola Di Giulio,Alvisa Palese,Valerio Dimonte,Sara Campagna | | Worldviews on Evidence-Based Nursing. 2019; | | [Pubmed] | [DOI] | | | 29 |
Modeling HPV vaccination scale-up among urban young men who have sex with men in the context of HIV |
|
| Neal D. Goldstein,Michael T. LeVasseur,Nguyen K. Tran,Jonathan Purtle,Seth L. Welles,Stephen C. Eppes | | Vaccine. 2019; | | [Pubmed] | [DOI] | | | 30 |
The effect of ‘Zesy002’ kiwifruit (Actinidia chinensis var. chinensis) on gut health function: a randomised cross-over clinical trial |
|
| Sarah L. Eady,Alison J. Wallace,Christine A. Butts,Duncan Hedderley,Lynley Drummond,Juliet Ansell,Richard B. Gearry | | Journal of Nutritional Science. 2019; 8 | | [Pubmed] | [DOI] | | | 31 |
Does Lifestyle Intervention After Gastric Bypass Surgery Prevent Weight Regain? A Randomized Clinical Trial |
|
| Susanna E. Hanvold,Kathrine J. Vinknes,Elin B. Løken,Anette Hjartåker,Ole Klungsøyr,Eline Birkeland,Hilde Risstad,Hanne L. Gulseth,Helga Refsum,Anne-Marie Aas | | Obesity Surgery. 2019; | | [Pubmed] | [DOI] | | | 32 |
The Effect of HIV Self-Testing Delivery Models on Female Sex Workers’ Sexual Behaviors: A Randomized Controlled Trial in Urban Uganda |
|
| Katrina F. Ortblad,Daniel Kibuuka Musoke,Thomson Ngabirano,Aidah Nakitende,Guy Harling,Jessica E. Haberer,Margaret McConnell,Joshua A. Salomon,Catherine E. Oldenburg,Till Bärnighausen | | AIDS and Behavior. 2019; | | [Pubmed] | [DOI] | | | 33 |
The effects of medication adherence on study outcomes in randomized clinical trials: a role for cognitive dysfunction? |
|
| V. Sanborn,M. A. Azcarate-Peril,J. Gunstad | | Applied Neuropsychology: Adult. 2019; : 1 | | [Pubmed] | [DOI] | | | 34 |
Effectiveness of prophylactic sacral protective dressings to prevent pressure injury: a systematic review and meta-analysis |
|
| Paul Fulbrook,Vainess Mbuzi,Sandra Miles | | International Journal of Nursing Studies. 2019; : 103400 | | [Pubmed] | [DOI] | | | 35 |
Iron-containing cookware for the reduction of iron deficiency anemia among children and females of reproductive age in low- and middle-income countries: A systematic review |
|
| Clark Alves,Ahlam Saleh,Halimatou Alaofè,Joann M. McDermid | | PLOS ONE. 2019; 14(9): e0221094 | | [Pubmed] | [DOI] | | | 36 |
Practical and Conceptual Considerations for the Primary Prevention of Asthma |
|
| Steven M. Brunwasser,Tina V. Hartert | | Clinics in Chest Medicine. 2019; 40(1): 1 | | [Pubmed] | [DOI] | | | 37 |
Response to Comment on “Letter to the Editor” |
|
| Hendrike E. Bolkenstein,Esther C. J. Consten,Ivo A. M. J. Broeders,Werner A. Draaisma | | Annals of Surgery. 2019; 270(6): e102 | | [Pubmed] | [DOI] | | | 38 |
A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis |
|
| Raimunda Nonata Ribeiro Sampaio,Juliana Saboia Fontenele e Silva,Carmen Dea Ribeiro de Paula,Cláudia Porto,Jorgeth de Oliveira Carneiro da Motta,Ledice Inacia de Araujo Pereira,Sofia Sales Martins,Daniel Holanda Barroso,Gustavo Subtil Magalhães Freire,Ciro Martins Gomes | | Revista da Sociedade Brasileira de Medicina Tropical. 2019; 52(0) | | [Pubmed] | [DOI] | | | 39 |
Variations in study outcomes relative to intention-to-treat and per-protocol data analysis techniques in the evaluation of efficacy for treatment of venous leg ulcers with dehydrated human amnion/chorion membrane allograft |
|
| Christian Bianchi,William Tettelbach,Niki Istwan,Brandon Hubbs,Kimberly Kot,Stan Harris,Donald Fetterolf | | International Wound Journal. 2019; | | [Pubmed] | [DOI] | | | 40 |
Effectiveness of Interventions for Preventing People With Dementia Exiting or Getting Lost |
|
| Luke Emrich-Mills,Vaisakh Puthusseryppady,Michael Hornberger,Patricia C. Heyn | | The Gerontologist. 2019; | | [Pubmed] | [DOI] | | | 41 |
Walking Green: Developing an Evidence Base for Nature Prescriptions |
|
| Elizabeth P.D. Koselka,Lucy C. Weidner,Arseniy Minasov,Marc G. Berman,William R. Leonard,Marianne V. Santoso,Junia N. de Brito,Zachary C. Pope,Mark A. Pereira,Teresa H. Horton | | International Journal of Environmental Research and Public Health. 2019; 16(22): 4338 | | [Pubmed] | [DOI] | | | 42 |
One Drop with an Activity Tracker for Adults with Type 1 Diabetes: Randomized Control Trial (Preprint) |
|
| Chandra Y. Osborn,Ashley Hirsch,Lindsay Sears,Mark Heyman,Jennifer Raymond,Brian Huddleston,Jeff Dachis | | JMIR mHealth and uHealth. 2019; | | [Pubmed] | [DOI] | | | 43 |
Effectiveness of deltamethrin-impregnated dog collars on the incidence of canine infection by Leishmania infantum: A large scale intervention study in an endemic area in Brazil |
|
| Wendel Coura-Vital,Gleisiane Gomes de Almeida Leal,Luana Araújo Marques,Aimara da Costa Pinheiro,Mariângela Carneiro,Alexandre Barbosa Reis,Knut Stieger | | PLOS ONE. 2018; 13(12): e0208613 | | [Pubmed] | [DOI] | | | 44 |
Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer: a register-based, observational study |
|
| Frederik Birkebæk Thomsen,Cecilia Bosco,Hans Garmo,Jan Adolfsson,Niklas Hammar,Pär Stattin,Mieke Van Hemelrijck | | Acta Oncologica. 2018; : 1 | | [Pubmed] | [DOI] | | | 45 |
Prevention Science and Child/Youth Development: Randomized Explanatory Trials for Integrating Theory, Method, and Analysis in Program Evaluation |
|
| James Jaccard,Ai Bo | | Journal of the Society for Social Work and Research. 2018; : 000 | | [Pubmed] | [DOI] | | | 46 |
Dietary therapy and non-surgical periodontal treatment in obese patients with chronic periodontitis |
|
| Mayte Martinez-Herrera,Sandra López-Domènech,Francisco Javier Silvestre,Javier Silvestre-Rangil,Celia Bañuls,Antonio Hernández-Mijares,Milagros Rocha | | Journal of Clinical Periodontology. 2018; | | [Pubmed] | [DOI] | | | 47 |
Assessment of collagen fiber orientation dispersion in articular cartilage by small-angle X-ray scattering and diffusion tensor imaging: Preliminary results |
|
| Sirisha Tadimalla,Monique C. Tourell,Robert Knott,Konstantin I. Momot | | Magnetic Resonance Imaging. 2018; | | [Pubmed] | [DOI] | | | 48 |
Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer’s disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients |
|
| Lídia Blanco-Silvente,Dolors Capellà,Josep Garre-Olmo,Joan Vilalta-Franch,Xavier Castells | | BMC Geriatrics. 2018; 18(1) | | [Pubmed] | [DOI] | | | 49 |
John Charnley Award |
|
| Michael J. Taunton,Robert T. Trousdale,Rafael J. Sierra,Ken Kaufman,Mark W. Pagnano | | Clinical Orthopaedics and Related Research. 2018; 476(2): 216 | | [Pubmed] | [DOI] | | | 50 |
Liuzijue Qigong vs traditional breathing training for patients with post-stroke dysarthria complicated with abnormal respiratory control: study protocol of a single center randomized controlled trial |
|
| Hongli Li,Gaiyan Li,Gongliang Liu,Ying Zhang | | Trials. 2018; 19(1) | | [Pubmed] | [DOI] | | | 51 |
Reducing Stress and Enhancing Academic Buoyancy among Adolescents Using a Brief Web-based Program Based on Acceptance and Commitment Therapy: A Randomized Controlled Trial |
|
| Anne Puolakanaho,Raimo Lappalainen,Päivi Lappalainen,Joona S. Muotka,Riikka Hirvonen,Kenneth M. Eklund,Timo P. S. Ahonen,Noona Kiuru | | Journal of Youth and Adolescence. 2018; | | [Pubmed] | [DOI] | | | 52 |
Elective replacement of intravenous cannula in neonates—a randomised trial |
|
| Li Yen Chin,Timothy A. Walsh,Karen Van Haltren,Laura Hayden,Miranda Davies-Tuck,Atul Malhotra | | European Journal of Pediatrics. 2018; | | [Pubmed] | [DOI] | | | 53 |
Konjenital Musku¨ler Tortikollis ve Birlikte Gelisen Deformasyonel Plagiosefalinin Ev Fizyoterapi Programina Yanitlarinin Incelenmesi |
|
| Hilal KEKLICEK,Fatma UYGUR | | Türk Fizyoterapi ve Rehabilitasyon Dergisi. 2017; | | [Pubmed] | [DOI] | | | 54 |
Efficacy of antidepressants: bias in randomized clinical trials and related issues |
|
| Sheng-Min Wang,Changsu Han,Soo-Jung Lee,Tae-Youn Jun,Ashwin A. Patkar,Prakash S. Masand,Chi-Un Pae | | Expert Review of Clinical Pharmacology. 2017; : 1 | | [Pubmed] | [DOI] | | | 55 |
Direct provision versus facility collection of HIV self-tests among female sex workers in Uganda: A cluster-randomized controlled health systems trial |
|
| Katrina Ortblad,Daniel Kibuuka Musoke,Thomson Ngabirano,Aidah Nakitende,Jonathan Magoola,Prossy Kayiira,Geoffrey Taasi,Leah G. Barresi,Jessica E. Haberer,Margaret A. McConnell,Catherine E. Oldenburg,Till Bärnighausen,Elvin H. Geng | | PLOS Medicine. 2017; 14(11): e1002458 | | [Pubmed] | [DOI] | |
|
 |
|
|
|
