BMJ 1999;319:670-674 ( 11 September )

Papers

What is meant by intention to treat analysis? Survey of published randomised controlled trials

Sally Hollis, senior lecturer ^a,  Fiona Campbell, statistician ^b. 

^a Medical Statistics Unit, Fylde College, Lancaster University, Lancaster LA1 4YF, ^b AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG

Correspondence to: S Hollis s.hollis{at}lancs.ac.uk

	Abstract

Top Abstract Introduction Methods Results Discussion References

Objectives: To assess the methodological quality of intention to treat analysis as reported in randomised controlled trials in four large medical journals.
Design: Survey of all reports of randomised controlled trials published in 1997 in the BMJ, Lancet, JAMA, and New England Journal of Medicine.
Main outcome measures: Methods of dealing with deviations from random allocation and missing data.
Results: 119 (48%) of the reports mentioned intention to treat analysis. Of these, 12 excluded any patients who did not start the allocated intervention and three did not analyse all randomised subjects as allocated. Five reports explicitly stated that there were no deviations from random allocation. The remaining 99 reports seemed to analyse according to random allocation, but only 34 of these explicitly stated this. 89 (75%) trials had some missing data on the primary outcome variable. The methods used to deal with this were generally inadequate, potentially leading to a biased treatment effect. 29 (24%) trials had more than 10% of responses missing for the primary outcome, the methods of handling the missing responses were similar in this subset.
Conclusions: The intention to treat approach is often inadequately described and inadequately applied. Authors should explicitly describe the handling of deviations from randomised allocation and missing responses and discuss the potential effect of any missing response. Readers should critically assess the validity of reported intention to treat analyses.

Key messages Intention to treat gives a pragmatic estimate of the benefit of a change in treatment policy rather than of potential benefit in patients who receive treatment exactly as planned Full application of intention to treat is possible only when complete outcome data are available for all randomised subjects About half of all published reports of randomised controlled trials stated that intention to treat was used, but handling of deviations from randomised allocation varied widely Many trials had some missing data on the primary outcome variable, and methods used to deal with this were generally inadequate, potentially leading to bias Intention to treat analyses are often inadequately described and inadequately applied

	Introduction

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"Intention to treat" is a strategy for the analysis of randomised controlled trials that compares patients in the groups to which they were originally randomly assigned. This is generally interpreted as including all patients, regardless of whether they actually satisfied the entry criteria, the treatment actually received, and subsequent withdrawal or deviation from the protocol. However there is a debate about the validity of excluding specific cases within each of these categories from an intention to treat analysis.¹ Clinical effectiveness may be overestimated if an intention to treat analysis is not done.²

The intention to treat approach has two main purposes. Firstly, the approach maintains treatment groups that are similar apart from random variation. This is the reason for randomisation, and the feature may be lost if analysis is not performed on the groups produced by the randomisation process. For example, in a trial comparing medical and surgical treatment for stable angina pectoris, some patients allocated to surgical intervention died before being operated on.³ If these deaths are not attributed to surgical intervention using an intention to treat analysis, surgery seems to have a falsely low mortality (table 1). Secondly, intention to treat analysis allows for non-compliance and deviations from policy by clinicians. There are, of course, exceptions. Some types of deviations from randomised allocation may occur only within the trial setting and would not be expected in routine practice. For example, in a trial comparing active and placebo vaccination there is the potential for placebo vaccine to be incorrectly administered in place of active, but this could not occur outside the trial and so need not be accounted for in estimates of potential efficacy. However, most types of deviations from protocol would continue to occur in routine practice and so should be included in the estimated benefit of a change in treatment policy. Intention to treat analysis is therefore most suitable for pragmatic trials⁴ of effectiveness rather than for explanatory investigations of efficacy.

View this table: [in this window] [in a new window]   Table 1. Use of intention to treat and other methods to analyse trial of coronary artery bypass surgery and medical treatment for stable angina pectoris in 768 men.2 Mortality 2 years after randomisation is shown by allocated and actual intervention*

Deviations from randomised allocation often result in missing outcome data. A full application of the intention to treat approach is possible only when complete outcome data are available for all randomised subjects. Care must always be taken to minimise missing responses and to follow up those who withdraw from treatment, but this is particularly important for the implementation of an intention to treat analysis.⁵ No consensus exists about how missing responses should be handled in intention to treat analyses, and different approaches may be appropriate in different situations. Practice also varies over handling of false inclusions (subjects found after randomisation not to satisfy the entry criteria). Thus, there is no single definition of an intention to treat analysis, and the phrase seems to have different meanings for different authors.⁶ We carried out a survey of recently published reports to examine current application of intention to treat analysis.

	Methods

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We identified all reports of randomised controlled trials published in 1997 in four major medical journals: BMJ, Lancet, JAMA, and New England Journal of Medicine. All except the New England Journal of Medicine have adopted the CONSORT statement,⁷ which requires that authors indicate whether analyses were performed on an intention to treat basis. The total number of randomised controlled trials was obtained by Medline searches for publication type "randomized controlled trials" within each journal and cross checked against the Cochrane controlled trials register.⁸ The journals were then hand searched to identify trials which reported an intention to treat analysis. For articles in the BMJ and Lancet, we also carried out a full text search for "intention to treat" or "intent to treat" on the internet (www.bmj.com, www.thelancet.com).

All trials that reported an intention to treat analysis were then independently assessed by both authors. We considered deviations from random allocation, false inclusions, and missing response. For each trial we recorded whether each of these occurred, and if so, the method of analysis and whether this method was explicitly stated. The assessment of missing response was limited to the primary outcomes if any were specified. Any uncertainties or disagreements between the two assessments were resolved by consensus.

	Results

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About half of all the randomised controlled trials reported an analysis explicitly described as intention to treat (table 2), with similar proportions in each journal. A total of 119 reports of randomised controlled trials including an intention to treat analysis were assessed. Table 3 summarises their characteristics.

View this table: [in this window] [in a new window]   Table 2. Randomised controlled trials identified for assessment

View this table: [in this window] [in a new window]   Table 3. Characteristics of intention to treat analyses

Most reports stated in the methods section that intention to treat analysis was used but did not specify how any deviations from randomised allocation, false inclusions, or missing outcomes were handled. Of the 15 reports that did not analyse according to randomised allocation, 12 specifically excluded from the analysis any patients who did not start the allocated intervention (table 4). Three papers described intention to treat analyses that do not comply with the basic principle of analysing all randomised subjects as allocated. In a report of a trial comparing conventional anterior surgery and laparoscopic surgery for repairing inguinal hernia, various patients were excluded, including those not receiving the allocated intervention:

Data on all patients who were randomly assigned ... were analysed on an intention to treat basis. In this analysis we did not include patients without hernias, those who withdrew their consent before undergoing surgery, those who at the time of surgery were found to be poor candidates for general anaesthesia, and those who did not undergo the assigned operation because of a misunderstanding resulting in an unplanned open or laparoscopic repair.²¹

This resulted in the exclusion of 57 (5%) enrolled patients.

View this table: [in this window] [in a new window]   Table 4. Trials in which patients who did not start allocated intervention were excluded from intention to treat analysis

In a trial of endometrial resection or hysterectomy for menorrhagia, the authors excluded from the intention to treat analysis 26 (13%) women who withdrew after randomisation but before surgery.²² The researchers contacted 10 of these women and found that, "of six who had been assigned endometrial resection, four had hysterectomy and two had resection, whereas three of four assigned hysterectomy chose endometrial resection and one chose hysterectomy." In a trial of folic acid supplementation, 17 (14%) women were excluded because of non-compliance.²³ The aim of this trial was to predict the likely effect of food fortification, which would not provide the same opportunity for non-compliance as supplementation using tablets. Thus, exclusion of women who did not comply was appropriate, but it should not have been described as an intention to treat analysis.

Five reports explicitly stated that there were no deviations from random allocation. The remaining 99 reports seemed to analyse according to random allocation, but only 34 of these explicitly stated this. Of the 25 reports which stated that false inclusions had occurred, only a quarter included these cases in the reported intention to treat analysis (table 3).

Eighty nine trials had some missing data on the primary outcome variable. The most common method of handling missing data was complete case analysis (44, 49%), in which all patients with a missing response are excluded from the analysis. Twenty nine (33%) papers used all available information on each patient (28 censored at end of follow up and one used all available outcome measurements over five assessments). Fifteen (17%) imputed values for the missing response. The imputation methods used were carry forward of last observed response (seven), explicit allocation of poor outcome (four), implicit assumption of good or poor outcome by including patients with missing response in the denominator but not the numerator when calculating rates (three), and use of the group average (one). Only one paper examined the effect of using a range of methods to handle the missing responses.²⁴ Twenty nine (24%) trials had more than 10% of responses missing for the primary outcome, the methods of handling the missing responses were similar in this subset.

	Discussion

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Almost half the reports of randomised controlled trials included an analysis described as intention to treat. This compares with 12% of trials found in a survey of reports published in obstetric and gynaecological journals in 1990-1.²⁵ Evidence based health care encourages appraisal of research methods, and critical appraisal guides for trials usually include a question on whether follow up was complete and whether subjects have been analysed in the groups to which they were randomised.²⁶ This increased general awareness of intention to treat analysis may have contributed to its incomplete use in the analysis of randomised controlled trials. The trials may have not been planned with a complete strategy for the reduction and handling of deviations from the allocated intervention.

Failure to start intervention
The exclusion of patients who did not start the allocated intervention from the intention to treat analysis was fairly common (10%). In some situations this seems sensible and is unlikely to lead to biaswhen the intended effect of an intervention depends on the occurrence of a subsequent event that cannot be influenced by the randomised allocation. For example, prophylaxis for prevention of transplant rejection can be effective only if a transplant is received; it seems unlikely that allocation to active treatment or placebo could affect this. Ideally, these situations should be avoided by randomisation after the necessary event, but this is not always possible in practice. Perhaps more could be achieved towards appropriate timing of randomisation, as illustrated by the surgeon who ensured randomisation after diagnosis by tossing a sterilised coin in the operating theatre once the patient's abdomen was open.²⁷ Unless the possibility of bias can be confidently rejected, patients who did not start the allocated intervention should be included in the intention to treat analysis where possible.

Non-compliance
If deviations from randomised allocation are due to non-compliance of the patient, the effect of the intervention if compliance had been complete may be relevant. However, naive comparisons based on compliance may be misleading. For example, the coronary drug project²⁸ found a substantially lower five year mortality in patients who complied well with clofibrate than in those who complied poorly, which seemed to indicate clofibrate was beneficial when taken as instructed. However, when compliance was examined in the placebo group, death rates in patients with both good and poor compliance were similar to those in the clofibrate group. The authors concluded that there are serious difficulties in evaluating treatment efficacy in subgroups defined by patient responses after randomisation. Considerable work has been carried out on valid statistical analysis of the effect of compliance in clinical trials,^29-32 but this is a complex area and should be approached with care.

False inclusions
False inclusions should also generally not be excluded from an intention to treat analysis.³³ Their exclusion can be justified only if the reascertainment of the entry criteria is applied identically in each group. From a pragmatic viewpoint, if false inclusions occur in the controlled environment of a trial, it seems inevitable that misclassification will also occur in routine clinical practice.

Missing response
The main problem in the application of intention to treat seen in this survey was the handling of missing response. Inappropriate handling of missing response can produce misleading conclusions. Table 5 shows the effect of various approaches. Complete case analysis, which was the approach used in most trials, violates the principle of intention to treat and leads to bias unless data are missing at randomthat is, absence of an observation is independent of the outcome. ^{35 36} Partial information, such as outcome at some time points, or time to drop out, may be used to produce a more efficient analysis, but this is still potentially biased.³⁷

View this table: [in this window] [in a new window]   Table 5. Effect of various methods of handling missing response in trial comparing balloon angioplast and stent placement for obstructed coronary bypass grafts34

Various imputation methods may be used to estimate the missing responses. However, clinical trials usually do not collect sufficient data to allow good estimation, and the only commonly feasible options are using the last observed response (carry forward) or assuming that all missing responses were constant. Extreme case analysis (for example, all patients lost to the group that fared better are assigned a poor outcome; all lost to the group that fared worse are assigned a good outcome) has also been recommended,³⁸ but this is unlikely to yield a conclusive answer in practice (Meyer K, Windeler J, 19th International Society for Clinical Biostatistics meeting, Dundee 1998). More sophisticated techniques for handling missing data are available³⁹ but depend on assumptions about the missing data mechanism which cannot be completely verified in most clinical trials. In general, imputation is used to produce a conservative estimate of treatment effect. However, no imputation method can give an unbiased estimate of the treatment effect unless the assumptions made about the missing data are valid. To fully appreciate the potential influence of missing responses, some form of sensitivity analysis is recommended, examining the effect of different strategies on the conclusions.

Recommendations for intention to treat analysis "ITT is better regarded as a complete trial strategy for design, conduct and analysis rather than as an approach to analysis alone"5 Design Decide whether the aim is pragmatic or explanatory. For pragmatic trials, intention to treat is essential Justify in advance any inclusion criteria which when violated would merit exclusion from intention to treat analysis Conduct Minimise missing response on the primary outcome Follow up subjects who withdraw from treatment Analysis Include all randomised subjects in the groups to which they were allocated Investigate the potential effect of missing response Reporting Specify that intention to treat analysis has been carried out, explicitly describing the handling of deviations from randomised allocation and missing response Report deviations from randomised allocation and missing response Discuss the potential effect of missing response Base conclusions on the results of intention to treat analysis

Implications
Full reporting of any deviations from random allocation and missing response is essential in the assessment of the necessity and appropriateness of an intention to treat approach, as emphasised in the CONSORT guidelines on the reporting of randomised controlled trials.⁷ However, the CONSORT guidelines do not address intention to treat analysis in any detail and so we have provided recommendations for its implementation (box).

Our survey revealed that the intention to treat approach is often inadequately described and inadequately applied. We hope that future researchers will take note of our recommendations, but we advise readers to assess critically the validity of reported intention to treat analyses.

	Acknowledgments

Contributors: SH initiated the research and is guarantor. SH and FC searched for eligible reports, assessed the reports, and participated in data analysis and writing of the paper.

	Footnotes

Funding: None.

Competing interests: None declared.

	References

Top Abstract Introduction Methods Results Discussion References

1.	Fisher LD, Dixon DO, Herson J, Frankowski RK, Hearon MS, Pearce KE. Intention to treat in clinical trials. In: Pearce KE, ed. Statistical issues in drug research and development. New York: Marcel Dekker, 1990:331-350.
2.	Bollini P, Pampallona S, Tibaldi G, Kupelnick B, Munizza C. Effectiveness of antidepressants. Meta-analysis of dose-effect relationships in randomised clinical trials. Br J Psychiatry 1999; 174: 297-300[Abstract/Free Full Text].
3.	European Coronary Surgery Study Group. Coronary-artery bypass surgery in stable angina pectoris: Survival at two years. Lancet 1979; i: 889-893.
4.	Roland M, Torgerson DJ. Understanding controlled trials. What are pragmatic trials?. BMJ 1998; 316: 285[Free Full Text].
5.	Lewis JA, Machin D. Intention to treatwho should use ITT? Br J Cancer 1993; 68: 647-650[Medline].
6.	Issues in trial reporting. Bandolier 1996; 3: 6-7.
7.	Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA 1996; 276: 637-639[Medline].
8.	Cochrane Controlled Trials Register. Cochrane library. Cochrane Collaboration. Oxford: Update Software , 1997.
9.	Spruance SL, Rea TL, Yhoming C, Tucker R, Saltzman R, Boon R. Penciclovir cream for the treatment of herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group. JAMA 1997; 277: 1374-1379[Abstract].
10.	Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B. Randomised placebo controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group. Lancet 1997; 349: 589-593[Medline].
11.	CAESAR Coordinating Committee. Randomised trail of addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens for patients with HIV-1 infection: the CAESAR trial. Lancet 1997; 349: 1413-1421[Medline].
12.	Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 1997; 350: 535-540[Medline].
13.	Rutgeerts P, Rauws E, Wara P, Swain P, Hoos A, Solleder E, et al. Randomised trial of single and repeated fibrin glue compared with injection of polidocanol treatment of bleeding peptic ulcer. Lancet 1997; 350: 692-696[Medline].
14.	Nashan B, Moore R, Amlot P, Schmidt AG, Abeywickrama K, Soulillou JP. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet 1997; 350: 1193-1198[Medline].
15.	Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 1997; 336: 1487-1493[Abstract/Free Full Text].
16.	Kaplan LD, Straus DJ, Testa MA, Von Roenn J, Dezube BJ, Cooley TP, et al. Low dose compared with standard dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 1997; 336: 1641-1648[Abstract/Free Full Text].
17.	Englund JA, Baker CJ, Raskino C, McKinney RE, Petrie B, Fowler MG, et al. Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group Study 152 Team. N Engl J Med 1997; 336: 1704-1712[Abstract/Free Full Text].
18.	Tardif JC, Cote G, Lesperance J, Bourassa M, Lambert J, Doucet S, et al. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. Multivitamins and Probuco Study Group. N Engl J Med 1997; 337: 365-372[Abstract/Free Full Text].
19.	Guilhot F, Chastang C, Michallot M, Guerci A, Harousseau JL, Maloisel F, et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group. N Engl J Med 1997; 337: 223-229[Abstract/Free Full Text].
20.	Daoud EG, Strickberger SA, Man KC, Goyal R, Deeb GM, Bolling SF, et al. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med 1997; 337: 1785-1791[Abstract/Free Full Text].
21.	Liem MS, van der Graaf Y, van Steensel CJ, Boelhouwer RU, Clevers GJ, Meijer W, et al. Comparison of conventional anterior surgery and laparoscopic surgery for inguinal-hernia repair. N Engl J Med 1997; 336: 1541-1547[Abstract/Free Full Text].
22.	O'Connor H, Broadbent JA, Magos AL, McPherson K. Medical Research Council randomised trial of endometrial resection versus hysterectomy in management of menorrhagia. Lancet 1997; 349: 879-901.
23.	Daly S, Mills JL, Molloy AM, Conley IM, Lee YJ, Kirke PN, et al. Minimum effective dose of folic acid for food fortification to prevent neural-tube defects. Lancet 1997; 350: 1662-1665[Medline].
24.	Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med 1997; 336: 153-162[Abstract/Free Full Text].
25.	Schulz KF, Grimes DA, Altman DG, Hayes RJ. Blinding and exclusions after allocation in randomised controlled trials: survey of published parallel group trials in obstetrics and gynaecology. BMJ 1996; 312: 742-744[Abstract/Free Full Text].
26.	Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature.2. How to use an article about therapy or prevention. A. Are the results of the study valid? JAMA 1993; 270: 2598-2601[Free Full Text].
27.	Newell DJ. Intention-to-treat analysis: implications for quantitative and qualitative research. Int J Epidemiol 1992; 21: 837-841[Abstract/Free Full Text].
28.	Coronary Drug Project Research Group. Influence of adherence to treatment and response of cholesterol on mortality in the coronary drug project. N Engl J Med 1980; 303: 1038-1041[Abstract].
29.	Cuzick J, Edwards R, Segnan N. Adjusting for non-compliance and contamination in randomized clinical trials. Stat Med 1997; 16: 1017-1029[Medline].
30.	Efron B, Feldman D. Compliance as an explanatory variable in clinical trials. J Am Stat Assoc 1991; 86: 9-17.
31.	Goetghebeur EJ, Shapiro SH. Analysing non-compliance in clinical trials: ethical imperative or mission impossible? Stat Med 1996; 15: 2813-2826[Medline].
32.	Sommer A, Zeger SL. On estimating efficacy from clinical trials. Stat Med 1991; 10: 45-52[Medline].
33.	Senn SJ. Statistical issues in drug development Chichester: Wiley , 1997.
34.	Savage MP, Douglas Jr JS, Fischman DL, Pepine CJ, King III SB, Werner JA, et al. Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. N Engl J Med 1997; 337: 740-747[Abstract/Free Full Text].
35.	Little RA, Rubin DB. Statistical analysis with missing data. New York: Wiley , 1987.
36.	Choi SC, Lu IL. Effect of non-random missing data mechanisms in clinical trials. Stat Med 1995; 14: 2675-2684[Medline].
37.	Lagakos SW, Lim LL, Robins JM. Adjusting for early treatment termination in comparative clinical trials. Stat Med 1990; 9: 1417-1424[Medline].
38.	Sackett DL, Richardson WS, Rosenberg WS, Haynes RB. Evidence-based medicine. New York: Churchill Livingstone , 1997.
39.	Little R, Yau L. Intent-to-treat analysis for longitudinal studies with drop-outs. Biometrics 1996; 52: 1324-1333[Medline].

(Accepted 2 June 1999)

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© BMJ 1999

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• Brown, C H., Wyman, P. A, Guo, J., Pena, J. (2006). Dynamic wait-listed designs for randomized trials: new designs for prevention of youth suicide. Clin Trials 3: 259-271 [Abstract]  
• Kober, T., Trelle, S., Engert, A. (2006). Reporting of randomized controlled trials in Hodgkin lymphoma in biomedical journals.. JNCI J Natl Cancer Inst 98: 620-625 [Abstract] [Full text]  
• Cacchio, A., Paoloni, M., Barile, A., Don, R., de Paulis, F., Calvisi, V., Ranavolo, A., Frascarelli, M., Santilli, V., Spacca, G. (2006). Effectiveness of Radial Shock-Wave Therapy for Calcific Tendinitis of the Shoulder: Single-Blind, Randomized Clinical Study. ptjournal 86: 672-682 [Abstract] [Full text]  
• Dumville, J. C, Torgerson, D. J, Hewitt, C. E (2006). Reporting attrition in randomised controlled trials. BMJ 332: 969-971 [Full text]  
• Gluud, L. L. (2006). Bias in Clinical Intervention Research. Am J Epidemiol 163: 493-501 [Abstract] [Full text]  
• Lai, R., Chu, R., Fraumeni, M., Thabane, L. (2006). Quality of Randomized Controlled Trials Reporting in the Primary Treatment of Brain Tumors. JCO 24: 1136-1144 [Abstract] [Full text]  
• Marx, M. A., Rodriguez, C. V., Greenko, J., Das, D., Heffernan, R., Karpati, A. M., Mostashari, F., Balter, S., Layton, M., Weiss, D. (2006). Diarrheal Illness Detected Through Syndromic Surveillance After a Massive Power Outage: New York City, August 2003. Am. J. Public Health 96: 547-553 [Abstract] [Full text]  
• Berner, E. S., Houston, T. K., Ray, M. N., Allison, J. J., Heudebert, G. R., Chatham, W. W., Kennedy, J. I. Jr., Glandon, G. L., Norton, P. A., Crawford, M. A., Maisiak, R. S. (2006). Improving Ambulatory Prescribing Safety with a Handheld Decision Support System: A Randomized Controlled Trial. J. Am. Med. Inform. Assoc. 13: 171-179 [Abstract] [Full text]  
• Lee, C., Gong, Y., Brok, J., Boxall, E. H, Gluud, C. (2006). Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis. BMJ 332: 328-336 [Abstract] [Full text]  
• Munn, J., Herbert, R. D., Hancock, M. J., Gandevia, S. C. (2005). Training with unilateral resistance exercise increases contralateral strength. J. Appl. Physiol. 99: 1880-1884 [Abstract] [Full text]  
• Cicutto, L., Murphy, S., Coutts, D., O'Rourke, J., Lang, G., Chapman, C., Coates, P. (2005). Breaking the Access Barrier: Evaluating an Asthma Center's Efforts to Provide Education to Children With Asthma in Schools. Chest 128: 1928-1935 [Abstract] [Full text]  
• McManus, R J, Mant, J, Roalfe, A, Oakes, R A, Bryan, S, Pattison, H M, Hobbs, F D R (2005). Targets and self monitoring in hypertension: randomised controlled trial and cost effectiveness analysis. BMJ 331: 493- [Abstract] [Full text]  
• White, I. R (2005). Uses and limitations of randomization-based efficacy estimators. Stat Methods Med Res 14: 327-347 [Abstract]  
• Fritz, S. L., Light, K. E., Patterson, T. S., Behrman, A. L., Davis, S. B. (2005). Active Finger Extension Predicts Outcomes After Constraint-Induced Movement Therapy for Individuals With Hemiparesis After Stroke. Stroke 36: 1172-1177 [Abstract] [Full text]  
• Tuech, J J, Pessaux, P, Moutel, G, Thoma, V, Schraub, S, Herve, C (2005). Methodological quality and reporting of ethical requirements in phase III cancer trials. J. Med. Ethics 31: 251-255 [Abstract] [Full text]  
• Robertson, M. C., Campbell, A. J., Herbison, P. (2005). Statistical Analysis of Efficacy in Falls Prevention Trials. J. Gerontol. A Biol. Sci. Med. Sci. 60: 530-534 [Abstract] [Full text]  
• Bowen, M. E., Poehling, K. A., Gunn, V. L., Carroll, K. N., Callahan, S. T., Arbogast, P. G., Cooper, W. O. (2005). Does the Use of Oxycodone Affect Diagnostic Accuracy in Children With Acute Abdominal Pain?. Arch Pediatr Adolesc Med 159: 326-328 [Full text]  
• Brooks, D., O'Brien, K., Geddes, E L., Crowe, J., Reid, W D. (2005). Is inspiratory muscle training effective for individuals with cervical spinal cord injury? A qualitative systematic review. Clin Rehabil 19: 237-246 [Abstract]  
• Wood, A. M, White, I. R, Hillsdon, M., Carpenter, J. (2005). Comparison of imputation and modelling methods in the analysis of a physical activity trial with missing outcomes. Int J Epidemiol 34: 89-99 [Abstract] [Full text]  
• Tierney, J. F, Stewart, L. A (2005). Investigating patient exclusion bias in meta-analysis. Int J Epidemiol 34: 79-87 [Abstract] [Full text]  
• Juni, P., Egger, M. (2005). Commentary: Empirical evidence of attrition bias in clinical trials. Int J Epidemiol 34: 87-88 [Full text]  
• Doig, G. S., Simpson, F., Delaney, A. (2005). A Review of the True Methodological Quality of Nutritional Support Trials Conducted in the Critically Ill: Time for Improvement. Anesth. Analg. 100: 527-533 [Abstract] [Full text]  
• Landorf, K. B., Keenan, A.-M., Herbert, R. D. (2004). Effectiveness of Different Types of Foot Orthoses for the Treatment of Plantar Fasciitis. J. Am. Podiatr. Med. Assoc. 94: 542-549 [Abstract] [Full text]  
• Krebs, E. E., Ensrud, K. E., MacDonald, R., Wilt, T. J. (2004). Phytoestrogens for Treatment of Menopausal Symptoms: A Systematic Review. Obstet Gynecol 104: 824-836 [Abstract] [Full text]  
• Wood, A. M, White, I. R, Thompson, S. G (2004). Are missing outcome data adequately handled? A review of published randomized controlled trials in major medical journals. Clin Trials 1: 368-376 [Abstract]  
• HUNG, L. Q., DE VRIES, P. J., BINH, T. Q., GIAO, P. T., NAM, N. V., HOLMAN, R., KAGER, P. A. (2004). ARTESUNATE WITH MEFLOQUINE AT VARIOUS INTERVALS FOR NON-SEVERE PLASMODIUM FALCIPARUM MALARIA. Am J Trop Med Hyg 71: 160-166 [Abstract] [Full text]  
• Helbostad, J. L, Sletvold, O., Moe-Nilssen, R. (2004). Home training with and without additional group training in physically frail old people living at home: effect on health-related quality of life and ambulation. Clin Rehabil 18: 498-508 [Abstract]  
• Als-Nielsen, B., Gluud, L. L, Gluud, C. (2004). Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. BMJ 328: 1046- [Abstract] [Full text]  
• Stolk, P., ten Berg, M. J, Hemels, M. E., Einarson, T. R (2003). Meta-Analysis of Placebo Rates in Major Depressive Disorder Trials. The Annals of Pharmacotherapy 37: 1891-1899 [Abstract] [Full text]  
• Puffer, S., Torgerson, D., Watson, J. (2003). Evidence for risk of bias in cluster randomised trials: review of recent trials published in three general medical journals. BMJ 327: 785-789 [Abstract] [Full text]  
• DUNN, G., MARACY, M., DOWRICK, C., AYUSO-MATEOS, J. L., DALGARD, O. S., PAGE, H., LEHTINEN, V., CASEY, P., WILKINSON, C., VAZQUEZ-BARQUERO, J. L., WILKINSON, G. (2003). Estimating psychological treatment effects from a randomised controlled trial with both non-compliance and loss to follow-up. Br. J. Psychiatry 183: 323-331 [Abstract] [Full text]  
• Williams, H. C. (2003). Applying Trial Evidence Back to the Patient. Arch Dermatol 139: 1195-1200 [Full text]  
• Boutron, I., Tubach, F., Giraudeau, B., Ravaud, P. (2003). Methodological Differences in Clinical Trials Evaluating Nonpharmacological and Pharmacological Treatments of Hip and Knee Osteoarthritis. JAMA 290: 1062-1070 [Abstract] [Full text]  
• Vail, A., Gardener, E. (2003). Common statistical errors in the design and analysis of subfertility trials. Hum Reprod 18: 1000-1004 [Abstract] [Full text]  
• Schachter, C. L, Busch, A. J, Peloso, P. M, Sheppard, M S. (2003). Effects of Short Versus Long Bouts of Aerobic Exercise in Sedentary Women With Fibromyalgia: A Randomized Controlled Trial. ptjournal 83: 340-358 [Abstract] [Full text]  
• Hilton, P., Ward, K. L (2002). Pleasing some of the people none of the time. BMJ 325: 1361-1361 [Full text]  
• Pavelka, K., Gatterova, J., Olejarova, M., Machacek, S., Giacovelli, G., Rovati, L. C. (2002). Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis: A 3-Year, Randomized, Placebo-Controlled, Double-blind Study. Arch Intern Med 162: 2113-2123 [Abstract] [Full text]  
• Fergusson, D., Aaron, S. D, Guyatt, G., Hebert, P. (2002). Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis. BMJ 325: 652-654 [Full text]  
• van der Schaaf, I. C., Ruigrok, Y. M., Rinkel, G. J.E., Algra, A., van Gijn, J. (2002). Study Design and Outcome Measures in Studies on Aneurysmal Subarachnoid Hemorrhage. Stroke 33: 2043-2046 [Abstract] [Full text]  
• Huwiler-Muntener, K., Juni, P., Junker, C., Egger, M. (2002). Quality of Reporting of Randomized Trials as a Measure of Methodologic Quality. JAMA 287: 2801-2804 [Abstract] [Full text]  
• Lamb, S E, Bartlett, H P, Ashley, A, Bird, W (2002). Can lay-led walking programmes increase physical activity in middle aged adults? A randomised controlled trial. J. Epidemiol. Community Health 56: 246-252 [Abstract] [Full text]  
• Dey, P., Bundred, N., Gibbs, A., Hopwood, P., Baildam, A., Boggis, C., James, M., Knox, F., Leidecker, V., Woodman, C., Dixon, J M. (2002). Costs and benefits of a one stop clinic compared with a dedicated breast clinic: randomised controlled trial * Commentary: one stop clinics should not be abandoned. BMJ 324: 507-507 [Abstract] [Full text]  
• Williams, H. C. (2002). Prevention of Atopic Eczema: A Dream Not So Far Away?. Arch Dermatol 138: 391-392 [Full text]  
• Juni, P., Holenstein, F., Sterne, J., Bartlett, C., Egger, M. (2002). Direction and impact of language bias in meta-analyses of controlled trials: empirical study. Int J Epidemiol 31: 115-123 [Abstract] [Full text]  
• Saisto, T., Salmela-Aro, K., Nurmi, J.-E., Kononen, T., Halmesmaki, E. (2001). A Randomized Controlled Trial of Intervention in Fear of Childbirth. Obstet Gynecol 98: 820-826 [Abstract] [Full text]  
• Montori, V. M., Guyatt, G. H. (2001). Intention-to-treat principle. CMAJ 165: 1339-1341 [Full text]  
• Pouwer, F., Snoek, F. J., van der Ploeg, H. M., Ader, H. J., Heine, R. J. (2001). Monitoring of Psychological Well-Being in Outpatients With Diabetes: Effects on mood, HbA1c, and the patient's evaluation of the quality of diabetes care: a randomized controlled trial. Diabetes Care 24: 1929-1935 [Abstract] [Full text]  
• Moher, D., Schulz, K. F., Altman, D. G. (2001). The CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel-Group Randomized Trials. J. Am. Podiatr. Med. Assoc. 91: 437-442 [Abstract] [Full text]  
• Juni, P., Altman, D. G, Egger, M. (2001). Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 323: 42-46 [Full text]  
• Wiggers, J., Considine, R., Hazell, T., Haile, M., Rees, M., Daly, J. (2001). Increasing the Practice of Health Promotion Initiatives by Licensed Premises. Health Educ Behav 28: 331-340 [Abstract]  
• KEKKI, M., KURKI, T., PELKONEN, J., KURKINEN-RATY, M., CACCIATORE, B., PAAVONEN, J. (2001). Vaginal Clindamycin in Preventing Preterm Birth and Peripartal Infections in Asymptomatic Women With Bacterial Vaginosis: A Randomized, Controlled Trial. Obstet Gynecol 97: 643-648 [Abstract] [Full text]  
• Moher, D., Schulz, K. F., Altman, D., for the CONSORT Group, (2001). The CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel-Group Randomized Trials. JAMA 285: 1987-1991 [Abstract] [Full text]  
• Egger, M., Juni, P., Bartlett, C., for the CONSORT Group, (2001). Value of Flow Diagrams in Reports of Randomized Controlled Trials. JAMA 285: 1996-1999 [Abstract] [Full text]  
• Seers, K., Critelton, N. (2001). Quantitative research: Designs relevant to nursing and healthcare. Journal of Research in Nursing 6: 487-500 [Abstract]  
• Dowrick, C., Dunn, G., Ayuso-Mateos, J. L., Dalgard, O. S., Page, H., Lehtinen, V., Casey, P., Wilkinson, C., Vazquez-Barquero, J. L., Wilkinson, G. (2000). Problem solving treatment and group psychoeducation for depression: multicentre randomised controlled trial. BMJ 321: 1450-1450 [Abstract] [Full text]  
• Harrington, R., Peters, S., Green, J., Byford, S., Woods, J., McGowan, R. (2000). Randomised comparison of the effectiveness and costs of community and hospital based mental health services for children with behavioural disorders. BMJ 321: 1047-1050 [Abstract] [Full text]  
• Ruiz-Canela, M., Martínez-González, M. A., de Irala-Estévez, J. (2000). Intention to treat analysis is related to methodological quality. BMJ 320: 1007-1007 [Full text]  

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Intention to treat analysis in population based screening interventions

Tanya Hoare, et al.
bmj.com, 21 Sep 1999 [Full text]