The need to address treatment uncertainties

Ignoring uncertainties about the effects of treatments has led to avoidable suffering and deaths. To reduce this suffering and premature mortality, treatment uncertainties must be acknowledged and addressed, first by reviewing systematically what is already known, and then in well designed research to reduce continuing uncertainties.

222 RECORDS
20 ARTICLES
3 BLOGS

The need to address treatment uncertainties

Principles of Testing

Treatment comparisons are essential

Treatment comparisons must be fair

Biases

Double dummy

The play of chance

Bringing it all together for the benefit of patients and the public

James Lind LibraryIllustrating the development of fair tests of treatments in health care

The need to address treatment uncertainties

SORT date ▼ author

222 RECORDS

20 ARTICLES

3 BLOGS

Turner KM, Huntley A, Yardley T, Dawson S, Dawson S (2024) Defining usual care comparators when designing pragmatic trials of complex health interventions: a methodology review. Trials 25, 117. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-07956-7

Nørgaard B, Draborg E, Andreasen J, Juhl CB, Yost J, Brunnhuber K, Robinson KA, Lund H (2022) Systematic reviews are rarely used to inform study design - a systematic review and meta-analysis. Journal of Clinical Epidemiology 145: 1-13.

McLennan S, Nussbaumer-Streit B, Hemkens LG, Briel M (2021) Barriers and Facilitating Factors for Conducting Systematic Evidence Assessments in Academic Clinical Trials. JAMA Network Open. 4(11):e2136577. url: doi/org/10.1001/jamanetworkopen.2021.36577

RECOVERY Trial Team (2020) Randomized Evaluation of COVID019 Therapy (RECOVERY). RECOVERY Central Coordinating Office, Oxford. www.recoverytrial.net

Chalmers I (2017) The evolution of fair tests of treatments over two millennia: a 23 minute audio commentary. Edited by Hamish Chalmers, using unbroadcast recordings made by Freakonomics Radio, with permission.

Wartolowska KA, Collins GS, Hopewell S, Judge A, Dean BJF, Rombach I, Beard DJ, Carr AJ (2016) Feasibility of surgical randomised controlled trials with a placebo arm: a systematic review. BMJ Open 6: p.e010194.

Sackett DL (2015) Sackett DL. Interview in 2014 and 2015. Brian Haynes, ed. McMaster University.

Wartolowska K, Judge A, Hopewell S, Collins GS, Dean BJF, Rombach I, Brindley D, Savulescu J, Beard DJ, Carr AJ (2014) Use of placebo controls in the evaluation of surgery: systematic review. BMJ 348:g3253. doi: 10.1136/bmj.g3253.

Smith V, Clarke M, Devane D, Begley C, Shorter G, Maguire L (2013) SWAT 1: what effects do site visits by the principal investigator have on recruitment in a multicentre randomized trial? Journal of Evidence-Based Medicine 6(3), 136-137 https://onlinelibrary.wiley.com/doi/epdf/10.1111/jebm.12049

Chalmers I, Atkinson P, Fenton M, Firkins L, Crowe S, Cowan K (2013) Tackling treatment uncertainties together: the evolution of the James Lind Initiative, 2003-2013. Journal of the Royal Society of Medicine 106(12), 482-91.

Robinson KA, Goodman SN (2011) A systematic examination of the citation of prior research in reports of randomized, controlled trials. Annals of Internal Medicine 154(1): 50-55.

Clarke M, Loudon K (2011) Effects on patients of their healthcare practitioner's or institution's participation in clinical trials: a systematic review. Trials 12:16.

Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock S, Macleod M, Mignini LE, Jayaram P, Khan KS (2007) Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ 334:197-200.

Clarke L, Clarke M, Clarke T (2007) How useful are Cochrane reviews in identifying research needs? Journal of Health Services Research and Policy 12, 101-103. journals.sagepub.com/doi/10.1258/135581907780279648

Jones B, Kenward MG (2003) Design and Analysis of Cross-Over-Trials (2nd Ed). London and USA: Chapman and Hall.

Sandercock P, Roberts I (2002) Systematic reviews of animal experiments. Lancet 360:586. DOI:https://doi.org/10.1016/S0140-6736(02)09812-4.

Stangl D, Berry DA (2000) Meta-Analysis in Medicine and Health Policy. New York: Marcel Dekker, Inc.

Sutton AJ, Abrams KR, Jones DR, Sheldon T, Song F (2000) Methods for Meta-Analysis in Medical Research. Chichester: Wiley.

Murray DM (1998) Design and Analysis of Group Randomized Trials. New York: Oxford University Press Inc.

Fitzpatrick R, Davey C, Buxton MJ, Jones (1998) Evaluating patient-based outcome measures for use in clinical trials. Health Technology Assessment 2(14), i-iv, 1-74.

Simpson JM, Klar N, Donner A (1995) Accounting for cluster randomization: a review of primary prevention trials, 1990 through 1993. American Journal of Public Health 85:1378-1383.

Chalmers I (1995) What do I want from health research and researchers when I am a patient? BMJ 310(6990), 1315-8.

Chalmers I (1991) The perinatal research agenda: whose priorities? Birth 18(3), 137-41.

Donner A, Brown KS, Brasher P (1990) A methodological review of non-therapeutic intervention trials employing cluster randomization, 1979-1989. International Journal of Epidemiology 19:795-800.

O’Rourke K, Detsky AS (1989) Meta-analysis in medical research: strong encouragement for higher quality in individual research efforts. Journal of Clinical Epidemiology 42:1021-24.

Pocock SJ, Hughes MD (1989) Practical problems in interim analyses, with particular regard to estimation. Control Clinical Trials10 (4 Suppl):209S-221S.

Jenicek M (1989) Meta-analysis in medicine: where we are and where we want to go. Journal of Clinical Epidemiology 42:35-44.

Chalmers TC (1988) Data analysis for clinical medicine: the quantitative approach to patient care in gastroenterology. Rome: International University Press.

Jenicek M (1987) Méta-analyse en médecine. Évaluation et synthèse de l’information clinique et épidémiologique. [Meta-analysis in medicine: evaluation and synthesis of clinical and epidemiological information] St.Hyacinthe and Paris: EDISEM and Maloine Éditeurs.

Machin D, Campbell MJ (1987) Statistical Tables for the Design of Clinical Trials. Oxford: Blackwell scientific publications.

Peto J, Eden OB, Lilleyman J, Richards S (1986) Improvement in treatments for children with acute lymphoblastic leukaemia: The Medical Research Council UKALL Trials, 1972-84. Lancet 1:408-411.

Bulpitt CJ (1984) Randomised controlled clinical trials. The Hague: Martinus Nijhoff.

Pocock SJ (1983) Clinical trials: a practical approach. Chichester: John Wiley.

Chalmers TC, Smith JH, Blackburn B, Silverman B, Schroeder B, Reitman D, Ambroz A (1981) A method for assessing the quality of a randomized control trial. Controlled Clinical Trials 2: 31-49.

Sackett DL (1979) Bias in analytic research. Journal of Chronic Diseases 32:51-63.

Farquhar JW (1978) The community-based model of life style intervention trials. American Journal of Epidemiology 108:103-111.

Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. British Journal of Cancer 35:1-39. PMID 831755.

Pocock SJ (1977) Randomised clinical trials. BMJ 1:1661.

Bunker JP, Barnes BA, Mosteller F (1977) Costs, risks and benefits of surgery. Oxford: Oxford University Press.

Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG (1976) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. British Journal of Cancer 34:585-6.

Cornfield J (1976) Recent methodological contributions to clinical trials. American Journal of Epidemiology 104:408-421.

Chalmers TC (1975) Randomization of the first patient. Medical Clinics of North America 59:1035-1038.

Cochrane AL (1972) Effectiveness and Efficiency: random reflections on health services. London: Nuffield Provincial Hospitals Trust.

Cornfield J (1971) The University Group Diabetes Program: a further statistical analysis of the mortality findings. JAMA 217:1676-87.

Schwartz D, Flamant R, Lellouch J (1970) L’essai thérapeutique chez l‘homme. Paris: Flammarion.

Ley HL (1969) Antibiotic drugs: procedural and interpretive regulations. Federal Register Vol. 34, No. 180, pp14596-597.

Chalmers TC (1968) When should randomisation begin? Lancet 1:858.

Schwartz D, Lellouch J (1967) Explanatory and pragmatic attitudes in therapeutic trials. Journal of Chronic Diseases 20:637-48.

Schneiderman MA (1966) Therapeutic trials in cancer. Working paper prepared for WHO Expert Committee on Cancer Treatment, Geneva, Switzerland, 9-15 March 1965. WHO/CANC/66.66.

Pollock TM, Bell JA, Hill AB, Cockburn WC, Cvjetanović B, Evans DG, Kostrzewski J, Schofield FD (1966) Trials of Prophylactic agents for the control of communicable diseases: a guide to their organization and evaluation‎. Geneva: World Health Organization.

Mainland D (1963) Elementary medical statistics: 2nd edn. Philadelphia: WB Saunders Co.

Hill AB (1962) Alfred Watson Memorial Lecture: The Statistician in Medicine. Journal of the Institute of Actuaries 88:178-191. doi:10.1017/S0020268100014980

Cochran WG (1961) Designing clinical trials. In: Forster FM, ed. Evaluation of drug therapy. University of Wisconsin Press, pp 71-77.

Schwartz D, Flamant R, Lellouch J, Rouquette C (1960) Les essais thérapeutiques cliniques [Controlled clinical trials]. Paris: Masson.

Hill AB (1960) Controlled clinical trials. Oxford: Blackwell Scientific Publications.

Mainland D (1960) The use and misuse of statistics in medical publications. Clinical Pharmacology and Therapeutics 1:411-22.

Waife SO, Shapiro AP (1959) The clinical evaluation of new drugs. New York: Hoeber-Harper.

Bull JP (1959) The historical development of clinical therapeutic trials. Journal of Chronic Diseases 10:218-248.

Witts LJ (1959) Medical surveys and clinical trials: some methods and applications of group research in medicine. Oxford: Oxford University Press.

Oldham PD (1959) Clinical and field trials. Acta Medica Hungarica 14:313-326.

Doll R (1959) Practical problems of drug trials in clinical practice. Lawrence DR, ed. Quantitative methods in human pharmacology and therapeutics. Oxford: Pergamon Press, pp. 213-221.

Symposium on Clinical Trials RSM (1958) Report of a meeting held at the Royal Society of Medicine, London on 25th April 1958.

Cox DR (1958) Planning of experiments. London: Wiley.

Kerr DNS, Davidson S (1958) Gastrointestinal intolerance to oral iron preparations. Lancet 2:489-492.

Greiner T, Bross I, Gold H (1957) A method for evaluation of laxative habits in human subjects. Journal of Chronic Diseases 6:244-255.

Bjerkelund CJ (1957) The effect of long-term treatment with dicoumarol in myocardial infarction. A controlled clinical study. Acta Med Scand Suppl 330:1-212.

Lasagna L (1955) The controlled clinical trial: theory and practice. Journal of Chronic Diseases 1:353-367.

Herdan G (1955) Statistics of Therapeutic Trials. Amsterdam: Elsevier.

Hogben L (1954) The assessment of remedies. Medical Press 232:331-338.

Gaddum JH (1954) Clinical pharmacology. Proceedings of the Royal Society of Medicine 47:195-204.

Hill AB (1952) The clinical trial. New England Journal of Medicine 247:113-119.

Hill AB (1951) The clinical trial. British Medical Bulletin 7:278-282.

Daniels M (1951) Clinical evaluation of chemotherapy in tuberculosis. British Medical Bulletin 7:320-326.

Ross OB (1951) The use of controls in medical research. JAMA 145:72-75.

James Lind Library
Illustrating the development of fair tests of treatments in health care

Turner KM, Huntley A, Yardley T, Dawson S, Dawson S (2024)
Defining usual care comparators when designing pragmatic trials of complex health interventions: a methodology review. Trials 25, 117. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-07956-7

Nørgaard B, Draborg E, Andreasen J, Juhl CB, Yost J, Brunnhuber K, Robinson KA, Lund H (2022)
Systematic reviews are rarely used to inform study design - a systematic review and meta-analysis. Journal of Clinical Epidemiology 145: 1-13.

McLennan S, Nussbaumer-Streit B, Hemkens LG, Briel M (2021)
Barriers and Facilitating Factors for Conducting Systematic Evidence Assessments in Academic Clinical Trials. JAMA Network Open. 4(11):e2136577. url: doi/org/10.1001/jamanetworkopen.2021.36577

RECOVERY Trial Team (2020)
Randomized Evaluation of COVID019 Therapy (RECOVERY). RECOVERY Central Coordinating Office, Oxford. www.recoverytrial.net

Chalmers I (2017)
The evolution of fair tests of treatments over two millennia: a 23 minute audio commentary. Edited by Hamish Chalmers, using unbroadcast recordings made by Freakonomics Radio, with permission.

Wartolowska KA, Collins GS, Hopewell S, Judge A, Dean BJF, Rombach I, Beard DJ, Carr AJ (2016)
Feasibility of surgical randomised controlled trials with a placebo arm: a systematic review. BMJ Open 6: p.e010194.

Sackett DL (2015)
Sackett DL. Interview in 2014 and 2015. Brian Haynes, ed. McMaster University.

Wartolowska K, Judge A, Hopewell S, Collins GS, Dean BJF, Rombach I, Brindley D, Savulescu J, Beard DJ, Carr AJ (2014)
Use of placebo controls in the evaluation of surgery: systematic review. BMJ 348:g3253. doi: 10.1136/bmj.g3253.

Smith V, Clarke M, Devane D, Begley C, Shorter G, Maguire L (2013)
SWAT 1: what effects do site visits by the principal investigator have on recruitment in a multicentre randomized trial? Journal of Evidence-Based Medicine 6(3), 136-137 https://onlinelibrary.wiley.com/doi/epdf/10.1111/jebm.12049

Chalmers I, Atkinson P, Fenton M, Firkins L, Crowe S, Cowan K (2013)
Tackling treatment uncertainties together: the evolution of the James Lind Initiative, 2003-2013. Journal of the Royal Society of Medicine 106(12), 482-91.

Robinson KA, Goodman SN (2011)
A systematic examination of the citation of prior research in reports of randomized, controlled trials. Annals of Internal Medicine 154(1): 50-55.

Clarke M, Loudon K (2011)
Effects on patients of their healthcare practitioner's or institution's participation in clinical trials: a systematic review. Trials 12:16.

Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock S, Macleod M, Mignini LE, Jayaram P, Khan KS (2007)
Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ 334:197-200.

Clarke L, Clarke M, Clarke T (2007)
How useful are Cochrane reviews in identifying research needs? Journal of Health Services Research and Policy 12, 101-103. journals.sagepub.com/doi/10.1258/135581907780279648

Jones B, Kenward MG (2003)
Design and Analysis of Cross-Over-Trials (2nd Ed). London and USA: Chapman and Hall.

Sandercock P, Roberts I (2002)
Systematic reviews of animal experiments. Lancet 360:586. DOI:https://doi.org/10.1016/S0140-6736(02)09812-4.

Stangl D, Berry DA (2000)
Meta-Analysis in Medicine and Health Policy. New York: Marcel Dekker, Inc.

Sutton AJ, Abrams KR, Jones DR, Sheldon T, Song F (2000)
Methods for Meta-Analysis in Medical Research. Chichester: Wiley.

Murray DM (1998)
Design and Analysis of Group Randomized Trials. New York: Oxford University Press Inc.

Fitzpatrick R, Davey C, Buxton MJ, Jones (1998)
Evaluating patient-based outcome measures for use in clinical trials. Health Technology Assessment 2(14), i-iv, 1-74.

Simpson JM, Klar N, Donner A (1995)
Accounting for cluster randomization: a review of primary prevention trials, 1990 through 1993. American Journal of Public Health 85:1378-1383.

Chalmers I (1995)
What do I want from health research and researchers when I am a patient? BMJ 310(6990), 1315-8.

Chalmers I (1991)
The perinatal research agenda: whose priorities? Birth 18(3), 137-41.

Donner A, Brown KS, Brasher P (1990)
A methodological review of non-therapeutic intervention trials employing cluster randomization, 1979-1989. International Journal of Epidemiology 19:795-800.

O’Rourke K, Detsky AS (1989)
Meta-analysis in medical research: strong encouragement for higher quality in individual research efforts. Journal of Clinical Epidemiology 42:1021-24.

Pocock SJ, Hughes MD (1989)
Practical problems in interim analyses, with particular regard to estimation. Control Clinical Trials10 (4 Suppl):209S-221S.

Jenicek M (1989)
Meta-analysis in medicine: where we are and where we want to go. Journal of Clinical Epidemiology 42:35-44.

Chalmers TC (1988)
Data analysis for clinical medicine: the quantitative approach to patient care in gastroenterology. Rome: International University Press.

Jenicek M (1987)
Méta-analyse en médecine. Évaluation et synthèse de l’information clinique et épidémiologique. [Meta-analysis in medicine: evaluation and synthesis of clinical and epidemiological information] St.Hyacinthe and Paris: EDISEM and Maloine Éditeurs.

Machin D, Campbell MJ (1987)
Statistical Tables for the Design of Clinical Trials. Oxford: Blackwell scientific publications.

Peto J, Eden OB, Lilleyman J, Richards S (1986)
Improvement in treatments for children with acute lymphoblastic leukaemia: The Medical Research Council UKALL Trials, 1972-84. Lancet 1:408-411.

Bulpitt CJ (1984)
Randomised controlled clinical trials. The Hague: Martinus Nijhoff.

Pocock SJ (1983)
Clinical trials: a practical approach. Chichester: John Wiley.

Chalmers TC, Smith JH, Blackburn B, Silverman B, Schroeder B, Reitman D, Ambroz A (1981)
A method for assessing the quality of a randomized control trial. Controlled Clinical Trials 2: 31-49.

Sackett DL (1979)
Bias in analytic research. Journal of Chronic Diseases 32:51-63.

Farquhar JW (1978)
The community-based model of life style intervention trials. American Journal of Epidemiology 108:103-111.

Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG (1977)
Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. British Journal of Cancer 35:1-39. PMID 831755.

Pocock SJ (1977)
Randomised clinical trials. BMJ 1:1661.

Bunker JP, Barnes BA, Mosteller F (1977)
Costs, risks and benefits of surgery. Oxford: Oxford University Press.

Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG (1976)
Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. British Journal of Cancer 34:585-6.

Cornfield J (1976)
Recent methodological contributions to clinical trials. American Journal of Epidemiology 104:408-421.

Chalmers TC (1975)
Randomization of the first patient. Medical Clinics of North America 59:1035-1038.

Cochrane AL (1972)
Effectiveness and Efficiency: random reflections on health services. London: Nuffield Provincial Hospitals Trust.

Cornfield J (1971)
The University Group Diabetes Program: a further statistical analysis of the mortality findings. JAMA 217:1676-87.

Schwartz D, Flamant R, Lellouch J (1970)
L’essai thérapeutique chez l‘homme. Paris: Flammarion.

Ley HL (1969)
Antibiotic drugs: procedural and interpretive regulations. Federal Register Vol. 34, No. 180, pp14596-597.

Chalmers TC (1968)
When should randomisation begin? Lancet 1:858.

Schwartz D, Lellouch J (1967)
Explanatory and pragmatic attitudes in therapeutic trials. Journal of Chronic Diseases 20:637-48.

Schneiderman MA (1966)
Therapeutic trials in cancer. Working paper prepared for WHO Expert Committee on Cancer Treatment, Geneva, Switzerland, 9-15 March 1965. WHO/CANC/66.66.

Pollock TM, Bell JA, Hill AB, Cockburn WC, Cvjetanović B, Evans DG, Kostrzewski J, Schofield FD (1966)
Trials of Prophylactic agents for the control of communicable diseases: a guide to their organization and evaluation‎. Geneva: World Health Organization.

Mainland D (1963)
Elementary medical statistics: 2nd edn. Philadelphia: WB Saunders Co.

Hill AB (1962)
Alfred Watson Memorial Lecture: The Statistician in Medicine. Journal of the Institute of Actuaries 88:178-191. doi:10.1017/S0020268100014980

Cochran WG (1961)
Designing clinical trials. In: Forster FM, ed. Evaluation of drug therapy. University of Wisconsin Press, pp 71-77.

Schwartz D, Flamant R, Lellouch J, Rouquette C (1960)
Les essais thérapeutiques cliniques [Controlled clinical trials]. Paris: Masson.

Hill AB (1960)
Controlled clinical trials. Oxford: Blackwell Scientific Publications.

Mainland D (1960)
The use and misuse of statistics in medical publications. Clinical Pharmacology and Therapeutics 1:411-22.

Waife SO, Shapiro AP (1959)
The clinical evaluation of new drugs. New York: Hoeber-Harper.

Bull JP (1959)
The historical development of clinical therapeutic trials. Journal of Chronic Diseases 10:218-248.

Witts LJ (1959)
Medical surveys and clinical trials: some methods and applications of group research in medicine. Oxford: Oxford University Press.

Oldham PD (1959)
Clinical and field trials. Acta Medica Hungarica 14:313-326.

Doll R (1959)
Practical problems of drug trials in clinical practice. Lawrence DR, ed. Quantitative methods in human pharmacology and therapeutics. Oxford: Pergamon Press, pp. 213-221.

Symposium on Clinical Trials RSM (1958)
Report of a meeting held at the Royal Society of Medicine, London on 25th April 1958.

Cox DR (1958)
Planning of experiments. London: Wiley.

Kerr DNS, Davidson S (1958)
Gastrointestinal intolerance to oral iron preparations. Lancet 2:489-492.

Greiner T, Bross I, Gold H (1957)
A method for evaluation of laxative habits in human subjects. Journal of Chronic Diseases 6:244-255.

Bjerkelund CJ (1957)
The effect of long-term treatment with dicoumarol in myocardial infarction. A controlled clinical study. Acta Med Scand Suppl 330:1-212.

Lasagna L (1955)
The controlled clinical trial: theory and practice. Journal of Chronic Diseases 1:353-367.

Herdan G (1955)
Statistics of Therapeutic Trials. Amsterdam: Elsevier.

Hogben L (1954)
The assessment of remedies. Medical Press 232:331-338.

Gaddum JH (1954)
Clinical pharmacology. Proceedings of the Royal Society of Medicine 47:195-204.

Hill AB (1952)
The clinical trial. New England Journal of Medicine 247:113-119.

Hill AB (1951)
The clinical trial. British Medical Bulletin 7:278-282.

Daniels M (1951)
Clinical evaluation of chemotherapy in tuberculosis. British Medical Bulletin 7:320-326.

Ross OB (1951)
The use of controls in medical research. JAMA 145:72-75.

Powers E, Witmer HL (1951)
An experiment in the prevention of delinquency: the Cambridge-Somerville Youth Study. New York: Columbia University Press.

Reid DD (1950)
Statistics in clinical research. Annals of the New York Academy of Sciences 52:931-934.

Editorial (1950)
Are statistics necessary? JAMA 143:1260-1261.

Marshall EK (1949)
Clinical therapeutic trial of a new drug. Bulletin of the Johns Hopkins Hospital 85:221-230.

Hinshaw HC, Feldman WH (1944)
Evaluation of therapeutic agents in clinical tuberculosis. American Review in Tuberculosis 50:202-213.