Correcting mortality for loss to follow-up: a nomogram applied to antiretroviral treatment programmes in sub-Saharan Africa.
BACKGROUND
The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART.


RESULTS
We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year.


CONCLUSIONS
The amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up.
Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland. egger@ispm.unibe.ch
Matthias
M
Egger
Ben D
BD
Spycher
John
J
Sidle
Ralf
R
Weigel
Elvin H
EH
Geng
Matthew P
MP
Fox
Patrick
P
MacPhail
Gilles
G
van Cutsem
Eugène
E
Messou
Robin
R
Wood
Denis
D
Nash
Margaret
M
Pascoe
Diana
D
Dickinson
Jean-François
JF
Etard
James A
JA
McIntyre
Martin W G
MW
Brinkhof
D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D000465:Algorithms; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015982:Bias; D002648:Child; D004363:Drug Utilization; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D049451:Nomograms; D010352:Patient Dropouts / Q000706:statistics & numerical data*; D015397:Program Evaluation / Q000706:statistics & numerical data
D019380:Anti-HIV Agents
Clin Infect Dis. 2005 Jul 15;41(2):217-24
15983918
Bull World Health Organ. 2007 Jul;85(7):550-4
17768504
PLoS Med. 2007 Oct 16;4(10):e298
17941716
Ann Intern Med. 2008 Aug 19;149(4):273-5
18711159
PLoS One. 2008;3(12):e3843
19048109
PLoS One. 2009 Jun 04;4(6):e5790
19495419
Int J Epidemiol. 2007 Apr;36(2):294-301
17213214
Lancet. 2006 Apr 22;367(9519):1335-42
16631912
Bull World Health Organ. 2008 Jul;86(7):559-67
18670668
Lancet. 2006 Aug 5;368(9534):505-10
16890837
Biometrics. 2001 Jun;57(2):333-42
11414553
Bull World Health Organ. 2008 Dec;86(12):939-47
19142294
Lancet. 2006 Mar 11;367(9513):817-24
16530575
Trop Med Int Health. 2010 Apr;15(4):405-13
20180931
J Acquir Immune Defic Syndr. 2008 Jan 1;47(1):101-7
17971708
Int J Epidemiol. 2007 Oct;36(5):969-76
17846055
JAMA. 2008 Aug 6;300(5):506-7
18677022
PLoS Med. 2009 Oct;6(10):e1000173
19859538
Bull World Health Organ. 2008 Sep;86(9):678-87
18797643
J Gen Intern Med. 2007 Dec;22(12):1745-50
17972138
JAMA. 2006 Aug 16;296(7):782-93
16905784
Trop Med Int Health. 2008 Jul;13(7):870-9
18373510
J Acquir Immune Defic Syndr. 2010 Mar;53(3):405-11
19745753
J Acquir Immune Defic Syndr. 2004 Mar 1;35(3):320-3
15076249
Int J Epidemiol. 2005 Oct;34(5):979-86
16157617
PLoS Med. 2008 Jul 8;5(7):e148
18613745
Lancet. 2010 Aug 7;376(9739):449-57
20638120
Acad Med. 2007 Aug;82(8):812-8
17762264
JAMA. 2006 Aug 9;296(6):679-90
16896111