Interventions to control chronic non-communicable diseases: the role of randomised controlled trials

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Interventions to control chronic non-communicable
diseases the role of randomised controlled trials
K K CHENG ? ??
The University of Birmingham, United Kingdom
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Conference
Definition The confusion of one man multiplied
by the number present.
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Evidence Based Medicine

• Importance of evidence in assessing
  effectiveness of health care interventions
• Randomised controlled trials as gold standards

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Levels of evidence
Ia Evidence obtained from meta-analysis of
randomised controlled trials Ib Evidence
obtained from at least one randomised controlled
trial
IIa Evidence obtained from at least one
well-designed controlled study without
randomisation IIb Evidence obtained from at
least one other type of well-designed
quasi-experimental study
III Evidence obtained from well-designed
non-experimental descriptive studies, such as
comparative studies, correlation studies and case
control studies
IV Evidence obtained from expert committee
reports or opinions and/or clinical experience of
respected authorities. From Scottish Inter
Collegiate Guidelines network
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Two examples

• Hepatocellular carcinoma prevention using
  selenium
• Obesity prevention

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Hepatocellular carcinoma (HCC)

• One of the most important types of cancer in
  Chinese populations
• 250,000 male and 100,000 female deaths annually
• 10-12 of Chinese adults are lifelong carriers
  of the hepatitis B virus (HBV)
• 15-25 of them develop HCC
• Possible role of selenium in reducing risk

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Selenium and HCCLaboratory evidence

• Both initiation and post-initiation
• effects
• Essential components of antioxidant Immune
  system effects
• Potent inducer of apoptosis

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Selenium and HCCObservational epidemiology
Taiwan cohort (7,342 men, 4,841 being HbsAg
carriers)  Mean follow up of 5.3 years Quintile
of baseline Adjusted odds ratio for plasma
selenium HCC (95 CI) ----------------
---- ---------------------- Q1 (lowest)
1.00 Q2 0.52 (0.21 - 1.33) Q3 0.32 (
0.09 1.09) Q4 0.19 (0.05 0.75) Q5
(highest) 0.62 (0.21 1.86) Yu et al.
(1999)
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Selenium and HCCClinical trials evidence

• Qidong, Jiangsu Province
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• Very high incidence area
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• 4 clinical trials in 1980s and 1990s
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• Reported in
• Li WG, Zhu Y, Yan X, et al. Zhonghua Yu Fang Yi
  Xue Za Zhi 2000
• Yu SY, Zhu YJ, Li WG, et al. Biol Trace Elem.Res
  1991
• Yu SY, Zhu YJ, Li WG. Biol Trace Elem.Res 1997

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Township study

• Residents living in 5 townships at Qidoing
• From 1985 to 1992, a supplement of selenium
• fortified table salt in one township
• Plain table salt to other 4 control townships

• High risk families study 
• 2474 members of families with high risk of HCC
• 1444 participants received 200 ?g of selenium
  daily and 1030 received placebo for 2 years

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HbsAg carriers study 1

• 226 HBsAg carriers
• Randomly allocated to receive 200 ?g of
• selenium or placebo daily for 4 years

• HbsAg carriers study 2
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• 2065 carriers
• 1112 received 228 ?g selenium daily and
• 953 received placebo for 3 years

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Selenium and HCCSummarising clinical trials
evidence
A meta-analysis of four trials conducted in
Qidong, China.
Pooled odds ratio 0.52 (95 CI 0.41 - 0.66)
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Selenium and HCCLimitations of Qidong trials

• Inadequate (and/or inadequate description of) 
• Patient selection
• Randomisation
• Blinding
• Baseline characteristics of treated vs placebo
• groups
• Methods of follow up and diagnosis
• Data analyses

• Difficulties in interpreting the results
• Potential loss of opportunities for prevention

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• Selenium and HCC
• If there were  
• well conducted and well reported clinical
  trials 
• optimal dissemination of findings
• HBV carriers should
• either
• be taking selenium supplements for prevention (if
  good trials establish a true protective effect of
  selenium)

or they can be sure that no opportunities have
been lost (if good trials show no benefit)
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Obesity

• Likely to be one of the most important causes of
  chronic disease morbidity and mortality in the
  21st Century
• Causes cardiovascular diseases, diabetes and
  several types of cancers
• Emerging problem in Chinese populations

 
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Obesity prevention in children

• Multi-agency approach needed
• Individual
• Family
• Education
• Health service
• Transport
• Agriculture
• Treasury

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Obesity prevention in children

• Cochrane review (Campbell et al.)
• Ten clinical trials nine were done in western
  populations. One was in Thailand.
• Conclusions
• There is limited high quality data on
  effectiveness
• No generalisable conclusions can be drawn

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Obesity prevention in children

• Interventions have to be culturally appropriate,
  locally acceptable and feasible
• Trials therefore have to be done in the local
  environment
• Outside health care settings, involving families,
  schools and local communities
• Cluster trials likely to be more appropriate 
• Groups of individuals (eg families, schools) as
  units of
• study
• Very rarely done in Chinese populations
• Require special methodological considerations

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Conclusions

• Well conducted clinical trials are essential
  to determine the effectiveness of health care
  interventions.
• They may be therapeutic or preventive.
• They can take place in hospitals, primary
  care and community settings.
• The use of clinical trials needs to be
  promoted.

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Ways to promote clinical trials

• Ensure the acceptance by health policy makers,
  clinicians, patients and the public of the
  importance of clinical trials
• Adequate coverage in medical education
  (undergraduate and postgraduate)
• Research funding should be earmarked for the
  support of strategic RCTs in key areas
• Clinical trials units should be set up
  clinicians, trialists, statisticians, behavioural
  scientists, quality of life experts...
• Synthesising evidence Cochrane Collaboration
  and Centres
• Dissemination through high quality journals
• Input into policy making mechanisms new
  investments reserved for interventions proved to
  be effective?