Randomised controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1642 (Published 08 April 2010) Cite this as: BMJ 2010;340:c1642
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Editor, I read the recent publication on chlamydia screening with a
great interest. The report has an interesting conclusion that "Although
some evidence suggests that screening for chlamydia reduces rates of
pelvic inflammatory disease, especially in women with chlamydial infection
at baseline, the effectiveness of a single chlamydia test in preventing
pelvic inflammatory disease over 12 months may have been overestimated
[1]. " I accept that early detection by screening program might be a good
secondary prevention for Chlamydia trachomatis infection. However, is this
an actual cost effective approach has to be further assessed. The left
questions are a) which is the best and most cost effective laboratory
screening technique ?, b) to whom the screening should be applied ? and c)
is the screening practical and useful for all settings.
References
1. Oakeshott P, Kerry S, Aghaizu A, Atherton H, Hay S, Taylor-Robinson D,
Simms I, Hay P. Randomised controlled trial of screening for Chlamydia
trachomatis to prevent pelvic inflammatory disease: the POPI (prevention
of pelvic infection) trial. BMJ 2010; 340: c1642
Competing interests:
None declared
Competing interests: No competing interests
The authors of the POPI trial should be congratulated for their
effort to expand the body of evidence for - or against - Chlamydia
screening. Especially the 94% follow up is impressive in this young and
mobile group. Unfortunately due to lack of power no significant effect of
screening could be shown. Data however do suggest benefit for the screened
group. Among the positives in the deferred group, 9,5% developed clinical
PID, compared with only 1.6% in the screened group.
Several critical issues already have been mentioned by the authors, like
the fact that many PID are incident PID, occurring in persons who tested
negative at baseline. The authors suggest that these interval-infections
might be reduced by shortening the screening interval. But could this be
the answer and how short would this interval need to be, especially for
those youngsters who take testing as a strategy to prevent condom use?
Testing embedded within integrated sexual health care, focussing on
effective counselling and patient-centred management, is imperative, but
provides a huge challenge for most providers.
A very interesting finding of the study is the non-random testing
behaviour. Many women have been tested outside the study, and even more
among those in the deferred group that were positive at baseline. This is
interesting, not only because it blurs the potential impact of the one-off
screening effect between the screened and the deferred screening group,
but also because it fuels the debate about who is being tested, a crucial
issue for impact assessment. Many studies show that people in high risk
groups are missed and prevention programmes have a bias towards the
”worried welll” and the higher SES. This study shows that people at higher
risk, as demonstrated by their actual Chlamydia status, do make informed
choices on being tested. Incorporating information about who is being
tested in numerators of screening programmes might be vital information in
modelling impact of screening in sexual networks.
A more fundamental issue is the fact that the design of this study
focuses on clinical PID. Infertility clinics demonstrate however that the
majority of women with tubal factor infertility with high Chlamydia
Antibody Titer do not remember such a “typical” presentation of clinical
signs and symptoms. So clinical PID might not be a good marker for all
PID. The real outcome factor would be infertility, and to fuel cost
effectivity analysis we would like to have more evidence about realistic
parameters in the clinical pathway of Chlamydia infection - PID –
infertility.1
Screening for Chlamydia is screening for infectious disease. Both
patient indicators (major outcomes averted (MOA) as well as societal
indicators (prevention of transmission) are measures of impact. This study
only focuses at one screening round and focuses on individual
complications. Two trials are currently implemented to assess the public
health impact of screening, one in the Netherlands2 and one in Australia3,
trying to demonstrate impact of multiple screening rounds on forward
transmission.
Both impact parameters will need to be converted, not in MOA, but in
comparative cost effectivity analysis measures (burden of disease measures
like DALY or QUALY) to enable policy makers to prioritise prevention
programmes.
Although this RCT certainly adds to the body of evidence, more power
is needed to guide evidence-based implementation of national programmatic
Chlamydia screening.
Jan van Bergen , MD MPh, PhD. STI AIDS Netherlands
Program Coordinator Chlamydia Screening Implementation Programme The
Netherlands
1. Land JA, van Bergen JEAM, Morre SA, Postma MJ. Epidemiology of
Chlamydia trachomatis in women and the cost-effectiveness of screening.
Human Reproduction Update oct 2009, doi:10.1093/humupd/dmp035.
2. Chlamydia Screening Implementation in the Netherlands.
http://www.narcis.info/research/RecordID/OND1323893/Language/en
2. Jane S Hocking, Jennifer Walker, David Regan, et al. Chlamydia
screening — Australia should strive to achieve what others have not. MJA
2008; 188 (2): 106-108
Competing interests:
None declared
Competing interests: No competing interests
The Prevention of Pelvic Infection (POPI) trial by Oakeshott and
colleagues[1] produced a number of important findings that further our
understanding of the risk of acquiring pelvic inflammatory disease (PID)
following chlamydia infection and highlight the need for alternative study
designs if we are to further investigate the effectiveness of chlamydia
screening. The trial found that clinical PID rates in the POPI trial were
much lower than previously estimated,[2] but that chlamydia is an
important risk for PID. Of the 38 cases of PID diagnosed during the
trial, chlamydia results were available for 26 cases and of these, 16
(62%) tested positive for chlamydia. Factoring in the missing test
results for the other 12 cases, then between 42% (assume all 12 were
negative) and 73% (assume all 12 were positive) of PID cases were positive
for chlamydia. Using the results from the control group, we calculated the
population attributable risk fraction and found that 26% of PID diagnosed
during the trial was attributable to chlamydia at baseline. The POPI trial
also found that most PID was associated with incident chlamydia.
The POPI trial did not determine conclusively whether or not a once
off chlamydia screen and treatment provided any protection against
clinically diagnosed PID and we still do not know whether screening can be
effective at reducing chlamydia prevalence. However, the trial
highlighted the difficulties in using PID as the primary endpoint and also
showed that regular screening is needed because of the association of PID
with incident chlamydia. Additional pragmatic trials that involve
multiple screening rounds and use other endpoints, such as chlamydia
prevalence, are therefore still needed to measure effectiveness.
The Australian Government has funded the Australian Chlamydia Control
Effectiveness Pilot (ACCEPt) – a cluster randomised controlled trial
(ACTRN12610000297022) with multiple rounds of screening that aims to
assess whether an annual invitation for chlamydia screening for 16 to 29
year olds can reduce its prevalence in the population. Australia is well
placed to conduct such a trial because current screening levels are still
quite low (less than 9% of under 25 year olds).[3] The intervention will
be randomised at the postcode (town) level and all primary care clinics in
each town will be invited to participate. Cluster randomisation will
allow the intervention to be delivered to people within social/sexual
networks. General practitioners will receive a multifaceted intervention
to facilitate screening and annual recall. Chlamydia prevalence will be
estimated from a consecutive sample of patients attending intervention and
control clinics. We aim to enrol around 54 towns and compare chlamydia
prevalence before and after the intervention in around 3,500 people. The
premise of this trial is that increased screening can be achieved by a
supportive intervention and that once levels of screening are high enough
(more than 30%), the prevalence of chlamydia will fall.[4] This trial
might well be the last opportunity for a randomised evaluation of the
effectiveness of chlamydia screening as screening continues to be further
expanded in developed countries.
Jane S Hocking (1)
Christopher K Fairley (1,2)
Rebecca Guy (3)
Meredith Temple-Smith (4)
Basil Donovan( 3)
John Kaldor (3)
Matthew Law (3)
Jane Gunn (4)
Simone Poznanski (1)
Nicola Low (5)
1. Centre for Women’s Health, Gender and Society, Melbourne School of
Population Health, University of Melbourne, Victoria, Australia
2. Melbourne Sexual Health Centre, Victoria, Australia
3. National Centre in HIV Epidemiology and Clinical Research,
University of New South Wales, New South Wales, Australia
4. Department of General Practice, University of Melbourne, Victoria,
Australia
5. Institute of Social and Preventive Medicine, University of Bern,
Switzerland
References:
1. Oakeshott P, Kerry S, Aghaizu A, Atherton H, Hay S, Taylor-
Robinson D, et al. Randomised controlled trial of screening for Chlamydia
trachomatis to prevent pelvic inflammatory disease: the POPI (prevention
of pelvic infection) trial. British Medical Journal;340(apr08_1):c1642-.
2. Low N, Bender N, Nartey L, Shang A, Stephenson JM. Effectiveness
of chlamydia screening: systematic review. International Journal of
Epidemiology 2009;38:435-448.
3. Medicare Australia. Medical Benefits Schedule Item Statistics
69316, 69317, 69319 2010.
4. Regan D, Wilson D, Hocking J. Coverage is the key for effective
screening of Chlamydia trachomatis in Australia. Journal of Infectious
Diseases 2008;198(3):349-358.
Competing interests:
None declared
Competing interests: No competing interests
The idea of screening for chamydia in the general population is
practical as they are being screened for paps once in 1-3 years in the
reproductive age group. The problem is the lack of it being an effective
screening tool and cost effectiveness. Also the number needed to treat
would be too high.
Competing interests:
None declared
Competing interests: No competing interests
The best ever study on chlamydia screening does not support screening
Many people ought to be congratulated for this study: Mainly
Oaketshott et al (1) for providing what is likely to be the defining
study on chlamydia screening and the natural history of chlamydia in women
but also the funders of the study for supporting research on chlamydia
screening when a national policy decision has already been taken to
implement it, the ethics committee for allowing a non-treatment group and
the BMJ for publishing a study with a negative result.
Thanks to all of them we now know that the incidence of PID is lower than
anticipated (1.3% in screened women compared with 1.9% in controls -
`relative risk 0.65, 95% confidence interval 0.34 to 1.22), that in the
population studied most PID occurred in screen negative women and that PID
often follows incident (new) chlamydia infection.
This large RCT (n=2529) used appropriate outcomes and had an impressive
follow up rate (94%) for inner city highly mobile women. It did not find a
statistically significant impact of chlamydia screening on PID incidence.
Unlike Oakeshott et al we believe that the study was not underpowered. The
reason why this excellent study could not find a statistically significant
reduction in PID incidence was that screening preventable PID was too rare
to make it an important public health problem, one of the basic
requirements for any screening programme.
To prevent chlamydial PID through screening it has to have a latent period
when chlamydia is present but has not caused PID. The study by Oakeshott
et al suggests that chlamydial PID often follows incident chlamydia
infection. If this would be correct screening could not reduce PID
incidence, unless by reducing the prevalence it would also reduce the
incidence of chlamydia infection. The latter still needs to be shown.
We are now able to calculate the health service costs for the prevention
of chlamydial PID through screening (of women). Findings by Kermec et al
(2) suggest that the lowest unit cost of a chlamydia screening test that
could be achieved in the UK National chlamydia Screening Programme (NCSP)
is £33. Oakeshott et al estimated that if chlamydia screening could reduce
the incidence of PID 147 women need to be screened to prevent one case of
PID. If screened through the NCSP this would cost at least £4851 per case
of PID prevented. Chlamydia screening could have other benefits than the
prevention of PID which could lower the costs per harmful outcome
prevented. One the other hand it has yet to be shown that screening men as
undertaken by the NCSP reduces the risk of PID or its consequences (3).
The cost of one episode of PID prevented through screening is thus
unlikely to be lower than for example the £4055 base tariff for the care
of people with “Non-Transient Stroke or Cerebrovascular Accident, Nervous
system infections or Encephalopathy” (4).
If screen preventable chlamydial PID is not a serious public health
problem, if there is no latent period, if an excellent RCT could not find
a statistically significant benefit from screening and more quality of
life could be achieved if the money is spend on something else then we
need to ask ourselves if there are not better options to improve the
sexual and reproductive health of young women than chlamydia screening.
Screening and “treatment” for unmet contraceptive needs may be an obvious
candidate.
References
1 Oakeschott P et al Randomised controlled trial of screening for
Chlamydia trachomatisto prevent pelvic inflammatory disease: the POPI
(prevention of pelvic infection) trial BMJ 2010;340:c1642
2 Kermec M, Grant A, Adams E. Current costs of Chlamydia screening in the
community using a top-down and bottom up approach. Poster presented at the
Second Joint Conference of the British HIV Association and the British
Association for Sexual Health and HIV, Manchester 20-23 April 2010,
Abstract P181 in HIV Medicine Vol 11, Suppl 1 May 2010
3 U.S. Preventive Services Task Force. Screening for chlamydial
infection: U.S. Preventive Services Task Force recommendation statement.
Ann Intern Med. 2007 Jul 17;147(2):128-34. Epub 2007 Jun 18.
4 Department of Health; Confirmation of Payment by Results (PbR)
arrangements for 2010-11
http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/@ps/documents/digitalasset/dh_115626.xls#'8.
OPCS 4 Adult Orthopaedic'!A1 accessed 3.5.10
Competing interests:
None declared
Competing interests: No competing interests