Abstract
There is now widespread acknowledgement of the absence of a sound evidence base underpinning many of the decisions made in primary care. Randomised controlled trials represent the methodology of choicefor determining efficacy and effectiveness of interventions, yet researchers working in primary care have been reluctant to use intervention studies, favouring observational study designs. Unfamiliarity with the different trial designs now available, and the relative advantages and disadvantages conferred by each, may be one factor contributing to this paradox. In this paper, we consider the principal trial designs available to primary care researchers, discussing the contexts in which a particular design may prove most useful. This information will, we hope, also prove useful to primary care clinicians attempting to interpret trial findings.
Full Text
The Full Text of this article is available as a PDF (78.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alexander F. E., Anderson T. J., Brown H. K., Forrest A. P., Hepburn W., Kirkpatrick A. E., Muir B. B., Prescott R. J., Smith A. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet. 1999 Jun 5;353(9168):1903–1908. doi: 10.1016/s0140-6736(98)07413-3. [DOI] [PubMed] [Google Scholar]
- Altman D. G., Bland J. M. How to randomise. BMJ. 1999 Sep 11;319(7211):703–704. doi: 10.1136/bmj.319.7211.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Altman D. G., Bland J. M. Statistics notes. Units of analysis. BMJ. 1997 Jun 28;314(7098):1874–1874. doi: 10.1136/bmj.314.7098.1874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Altman D. G., Schulz K. F., Moher D., Egger M., Davidoff F., Elbourne D., Gøtzsche P. C., Lang T., CONSORT GROUP (Consolidated Standards of Reporting Trials) The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001 Apr 17;134(8):663–694. doi: 10.7326/0003-4819-134-8-200104170-00012. [DOI] [PubMed] [Google Scholar]
- Black N. Why we need observational studies to evaluate the effectiveness of health care. BMJ. 1996 May 11;312(7040):1215–1218. doi: 10.1136/bmj.312.7040.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brewin C. R., Bradley C. Patient preferences and randomised clinical trials. BMJ. 1989 Jul 29;299(6694):313–315. doi: 10.1136/bmj.299.6694.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Butler C., Bachmann M. Design and analysis of studies evaluating smoking cessation interventions where effects vary between practices or practitioners. Fam Pract. 1996 Aug;13(4):402–407. doi: 10.1093/fampra/13.4.402. [DOI] [PubMed] [Google Scholar]
- Chalmers I. What do I want from health research and researchers when I am a patient? BMJ. 1995 May 20;310(6990):1315–1318. doi: 10.1136/bmj.310.6990.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chilvers C., Dewey M., Fielding K., Gretton V., Miller P., Palmer B., Weller D., Churchill R., Williams I., Bedi N. Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms. BMJ. 2001 Mar 31;322(7289):772–775. doi: 10.1136/bmj.322.7289.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dexter P. R., Wolinsky F. D., Gramelspacher G. P., Zhou X. H., Eckert G. J., Waisburd M., Tierney W. M. Effectiveness of computer-generated reminders for increasing discussions about advance directives and completion of advance directive forms. A randomized, controlled trial. Ann Intern Med. 1998 Jan 15;128(2):102–110. doi: 10.7326/0003-4819-128-2-199801150-00005. [DOI] [PubMed] [Google Scholar]
- Donner A., Klar N. Statistical considerations in the design and analysis of community intervention trials. J Clin Epidemiol. 1996 Apr;49(4):435–439. doi: 10.1016/0895-4356(95)00511-0. [DOI] [PubMed] [Google Scholar]
- Duggan C. M., Mitchell G., Nikles C. J., Glasziou P. P., Del Mar C. B., Clavarino A. Managing ADHD in general practice. N of 1 trials can help! Aust Fam Physician. 2000 Dec;29(12):1205–1209. [PubMed] [Google Scholar]
- Edwards S. J., Braunholtz D. A., Lilford R. J., Stevens A. J. Ethical issues in the design and conduct of cluster randomised controlled trials. BMJ. 1999 May 22;318(7195):1407–1409. doi: 10.1136/bmj.318.7195.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elbourne D. R., Campbell M. K. Extending the CONSORT statement to cluster randomized trials: for discussion. Stat Med. 2001 Feb 15;20(3):489–496. doi: 10.1002/1097-0258(20010215)20:3<489::aid-sim806>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
- Fitzpatrick R., Davey C., Buxton M. J., Jones D. R. Evaluating patient-based outcome measures for use in clinical trials. Health Technol Assess. 1998;2(14):i-iv, 1-74. [PubMed] [Google Scholar]
- Gostick N., James I. G., Khong T. K., Roy P., Shepherd P. R., Miller A. J. Controlled-release indomethacin and sustained-release diclofenac sodium in the treatment of osteoarthritis: a comparative controlled clinical trial in general practice. Curr Med Res Opin. 1990;12(3):135–142. doi: 10.1185/03007999009111494. [DOI] [PubMed] [Google Scholar]
- Grant C. C., Duggan A. K., DeAngelis C. Independent parental administration of prednisone in acute asthma: a double-blind, placebo-controlled, crossover study. Pediatrics. 1995 Aug;96(2 Pt 1):224–229. [PubMed] [Google Scholar]
- Guyatt G., Sackett D., Adachi J., Roberts R., Chong J., Rosenbloom D., Keller J. A clinician's guide for conducting randomized trials in individual patients. CMAJ. 1988 Sep 15;139(6):497–503. [PMC free article] [PubMed] [Google Scholar]
- Horton R. Evidence and primary care. Lancet. 1999 Feb 20;353(9153):609–610. doi: 10.1016/S0140-6736(99)00056-2. [DOI] [PubMed] [Google Scholar]
- Jensen K., Tfelt-Hansen P., Hansen E. W., Krøis E. H., Pedersen O. S. Introduction of a novel self-injector for sumatriptan. A controlled clinical trial in general practice. Cephalalgia. 1995 Oct;15(5):423–429. doi: 10.1046/j.1468-2982.1995.1505423.x. [DOI] [PubMed] [Google Scholar]
- Kamien M. The use of an N-of-1 randomised clinical trial in resolving therapeutic doubt. The case of a patient with an 'attention disorder'. Aust Fam Physician. 1998 Jul;27 (Suppl 2):S103–S105. [PubMed] [Google Scholar]
- Karnon J., Qizilbash N. Economic evaluation alongside n-of-1 trials: getting closer to the margin. Health Econ. 2001 Jan;10(1):79–82. doi: 10.1002/1099-1050(200101)10:1<79::aid-hec567>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- Kendrick D., Marsh P., Fielding K., Miller P. Preventing injuries in children: cluster randomised controlled trial in primary care. BMJ. 1999 Apr 10;318(7189):980–983. doi: 10.1136/bmj.318.7189.980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kendrick T., Burns T., Freeling P. Randomised controlled trial of teaching general practitioners to carry out structured assessments of their long term mentally ill patients. BMJ. 1995 Jul 8;311(6997):93–98. doi: 10.1136/bmj.311.6997.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kent M. A., Camfield C. S., Camfield P. R. Double-blind methylphenidate trials: practical, useful, and highly endorsed by families. Arch Pediatr Adolesc Med. 1999 Dec;153(12):1292–1296. doi: 10.1001/archpedi.153.12.1292. [DOI] [PubMed] [Google Scholar]
- Kerry S. M., Bland J. M. The intracluster correlation coefficient in cluster randomisation. BMJ. 1998 May 9;316(7142):1455–1455. doi: 10.1136/bmj.316.7142.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kerse N. M., Flicker L., Jolley D., Arroll B., Young D. Improving the health behaviours of elderly people: randomised controlled trial of a general practice education programme. BMJ. 1999 Sep 11;319(7211):683–687. doi: 10.1136/bmj.319.7211.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magee L. A., Redman C. W. An N-of-1 trial for treatment of hyperemesis gravidarum. Br J Obstet Gynaecol. 1996 May;103(5):478–480. doi: 10.1111/j.1471-0528.1996.tb09779.x. [DOI] [PubMed] [Google Scholar]
- Mahon J. L., Laupacis A., Hodder R. V., McKim D. A., Paterson N. A., Wood T. E., Donner A. Theophylline for irreversible chronic airflow limitation: a randomized study comparing n of 1 trials to standard practice. Chest. 1999 Jan;115(1):38–48. doi: 10.1378/chest.115.1.38. [DOI] [PubMed] [Google Scholar]
- March L., Irwig L., Schwarz J., Simpson J., Chock C., Brooks P. n of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis. BMJ. 1994 Oct 22;309(6961):1041–1046. doi: 10.1136/bmj.309.6961.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McBride P., Underbakke G., Plane M. B., Massoth K., Brown R. L., Solberg L. I., Ellis L., Schrott H. G., Smith K., Swanson T. Improving prevention systems in primary care practices: the Health Education and Research Trial (HEART) J Fam Pract. 2000 Feb;49(2):115–125. [PubMed] [Google Scholar]
- Moffett J. K., Torgerson D., Bell-Syer S., Jackson D., Llewlyn-Phillips H., Farrin A., Barber J. Randomised controlled trial of exercise for low back pain: clinical outcomes, costs, and preferences. BMJ. 1999 Jul 31;319(7205):279–283. doi: 10.1136/bmj.319.7205.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montgomery A. A., Fahey T., Peters T. J., MacIntosh C., Sharp D. J. Evaluation of computer based clinical decision support system and risk chart for management of hypertension in primary care: randomised controlled trial. BMJ. 2000 Mar 11;320(7236):686–690. doi: 10.1136/bmj.320.7236.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nikles C. J., Glasziou P. P., Del Mar C. B., Duggan C. M., Mitchell G. N of 1 trials. Practical tools for medication management. Aust Fam Physician. 2000 Nov;29(11):1108–1112. [PubMed] [Google Scholar]
- Oakeshott P., Kerry S. M., Williams J. E. Randomized controlled trial of the effect of the Royal College of Radiologists' guidelines on general practitioners' referrals for radiographic examination. Br J Gen Pract. 1994 May;44(382):197–200. [PMC free article] [PubMed] [Google Scholar]
- Oakeshott P., Kerry S. M., Williams J. E. Randomized controlled trial of the effect of the Royal College of Radiologists' guidelines on general practitioners' referrals for radiographic examination. Br J Gen Pract. 1994 May;44(382):197–200. [PMC free article] [PubMed] [Google Scholar]
- Pedersen P. A., Johansen P. B. Prophylactic treatment of adult nocturia with bumetanide. Br J Urol. 1988 Aug;62(2):145–147. doi: 10.1111/j.1464-410x.1988.tb04294.x. [DOI] [PubMed] [Google Scholar]
- Peveler R., George C., Kinmonth A. L., Campbell M., Thompson C. Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. BMJ. 1999 Sep 4;319(7210):612–615. doi: 10.1136/bmj.319.7210.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Randomised controlled trial evaluating cardiovascular screening and intervention in general practice: principal results of British family heart study. Family Heart Study Group. BMJ. 1994 Jan 29;308(6924):313–320. [PMC free article] [PubMed] [Google Scholar]
- Roderick P., Ruddock V., Hunt P., Miller G. A randomized trial to evaluate the effectiveness of dietary advice by practice nurses in lowering diet-related coronary heart disease risk. Br J Gen Pract. 1997 Jan;47(414):7–12. [PMC free article] [PubMed] [Google Scholar]
- Russell M. B., Holm-Thomsen O. E., Rishøj Nielsen M., Cleal A., Pilgrim A. J., Olesen J. A randomized double-blind placebo-controlled crossover study of subcutaneous sumatriptan in general practice. Cephalalgia. 1994 Aug;14(4):291–296. doi: 10.1046/j.1468-2982.1994.1404291.x. [DOI] [PubMed] [Google Scholar]
- Smith P. G., Day N. E. The design of case-control studies: the influence of confounding and interaction effects. Int J Epidemiol. 1984 Sep;13(3):356–365. doi: 10.1093/ije/13.3.356. [DOI] [PubMed] [Google Scholar]
- Steptoe A., Doherty S., Rink E., Kerry S., Kendrick T., Hilton S. Behavioural counselling in general practice for the promotion of healthy behaviour among adults at increased risk of coronary heart disease: randomised trial. BMJ. 1999 Oct 9;319(7215):943–948. doi: 10.1136/bmj.319.7215.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tallon D., Chard J., Dieppe P. Relation between agendas of the research community and the research consumer. Lancet. 2000 Jun 10;355(9220):2037–2040. doi: 10.1016/S0140-6736(00)02351-5. [DOI] [PubMed] [Google Scholar]
- Thomas T., Fahey T., Somerset M. The content and methodology of research papers published in three United Kingdom primary care journals. Br J Gen Pract. 1998 May;48(430):1229–1232. [PMC free article] [PubMed] [Google Scholar]
- Tilyard M. W., Dovey S. M. A comparison of tiaprofenic acid, mefenamic acid and placebo in the treatment of dysmenorrhoea in general practice. Aust N Z J Obstet Gynaecol. 1992 May;32(2):165–168. doi: 10.1111/j.1479-828x.1992.tb01933.x. [DOI] [PubMed] [Google Scholar]
- Torgerson D. J. Contamination in trials: is cluster randomisation the answer? BMJ. 2001 Feb 10;322(7282):355–357. doi: 10.1136/bmj.322.7282.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Torgerson D. J., Klaber-Moffett J., Russell I. T. Patient preferences in randomised trials: threat or opportunity? J Health Serv Res Policy. 1996 Oct;1(4):194–197. doi: 10.1177/135581969600100403. [DOI] [PubMed] [Google Scholar]
- Torgerson D. J., Sibbald B. Understanding controlled trials. What is a patient preference trial? BMJ. 1998 Jan 31;316(7128):360–360. doi: 10.1136/bmj.316.7128.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ukoumunne O. C., Gulliford M. C., Chinn S., Sterne J. A., Burney P. G., Donner A. Methods in health service research. Evaluation of health interventions at area and organisation level. BMJ. 1999 Aug 7;319(7206):376–379. doi: 10.1136/bmj.319.7206.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vanmolkot F. H., de Hoon J. N., van de Ven L. L., Van Bortel L. M. Impact of antihypertensive treatment on quality of life: comparison between bisoprolol and bendrofluazide. J Hum Hypertens. 1999 Aug;13(8):559–563. doi: 10.1038/sj.jhh.1000868. [DOI] [PubMed] [Google Scholar]
- Ward E., King M., Lloyd M., Bower P., Sibbald B., Farrelly S., Gabbay M., Tarrier N., Addington-Hall J. Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. I: clinical effectiveness. BMJ. 2000 Dec 2;321(7273):1383–1388. doi: 10.1136/bmj.321.7273.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiebe E. N of 1 trials. Managing patients with chronic fatigue syndrome: two case reports. Can Fam Physician. 1996 Nov;42:2214–2217. [PMC free article] [PubMed] [Google Scholar]
- Woods J. R., Williams J. G., Tavel M. The two-period crossover design in medical research. Ann Intern Med. 1989 Apr 1;110(7):560–566. doi: 10.7326/0003-4819-110-7-560. [DOI] [PubMed] [Google Scholar]
- Zucker D. R., Schmid C. H., McIntosh M. W., D'Agostino R. B., Selker H. P., Lau J. Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol. 1997 Apr;50(4):401–410. doi: 10.1016/s0895-4356(96)00429-5. [DOI] [PubMed] [Google Scholar]
