Section Links

Clinical and Observational Studies Resource
Randomised Controlled Trials Resource
Qualitative (Descriptive) Studies Resource
Systematic Reviews Resource

Clinical and Observational Studies

What is a trial, what is a study, brief explanation of clinical and observational studies

The main ethical justification for performing research is the important benefit to society gained from health research – the potential value of future research, together with the contributions that research makes to improving the health and welfare of individuals and populations, for the public good. Promoting these goods justifies risking harms or limiting some other public or private benefits, for example if on placebo (Research within the privacy regulations: problems and solutions for database custodians. Ea Mulligan, W Rogers, A Braunack-Mayer South Australia on the web).

Ethical considerations:
- comparator used, use of placebo compared with usual care
- uncertainty principle applied
- informed consent obtained
- conduct of trial (stringent methodology).

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WHO Clinical Trials Registry Platform

“Clinical trials are important sources of scientific evidence on the safety and effectiveness of health interventions. Access to information about ongoing, completed and published clinical trials is essential for appropriate decision-making. Researchers, research funders, policy-makers, medical practitioners, patients and the general public need such information, to help guide research or to make treatment decisions” (www.who.int/ictrp).

The mission of the WHO Registry Platform is to ensure that a complete view of research is accessible to all those involved in health care decision making. This will improve research transparency and will ultimately strengthen the validity and value of the scientific evidence base.
The registration of all interventional trials is a scientific, ethical and moral responsibility.

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Observational Studies

They have their place:

Identifying predictors of disease, or risk factors
Large observational studies (in populations or cohorts) have shown smoking is a cause of lung cancer, sun exposure for skin cancer, mesothelioma among workers exposed to asbestos, sexual activity to spread the human papilloma virus that causes cervical cancer; high blood pressure is associated with an increased risk of heart disease and obesity is associated with an increased risk of most common chronic diseases.

For these studies people are exposed to some factor of interest (for example diet, exercise, supplements, occupation, eating large amounts of dietary fibre) at the start of the study and then followed over a time period sufficient to allow any effects of that exposure to occur and be measured.

Identifying (unexpected) side effects of treatment
Large observational studies are important to identify the adverse effects, unintended consequences or unexpected harms with interventions, for example higher rates of vaginal cancer among the daughters of mothers who took diethyl stilboestrol (DES) to prevent miscarriage or stillbirth (their offspring had a higher incidence of rare cancers and abnormalities of the reproductive system).

And limitations

The cohort studies are often based on physiological reasoning and expert opinion. In some cases, when randomised controlled trials were financed to test results from large observational studies, the findings were not confirmed.

Participants may have effectively self selected to be part of the studies. People who are well off and faithfully engage in activities that are good for them – taking a drug as prescribed, eating what they believe is a healthy diet, exercising, are fundamentally different from those who do not.

Hormone replacement therapy for post-menopausal women is an important example.
  • The Nurses’ Health Study of different cohorts (non-randomised, reported that hormone replacement therapy prevented heart disease and stroke.
  • Yet the large Women’s Health Initiative hormone-therapy randomised controlled trial (2002) failed to confirm these findings: while it may protect against osteoporosis and possibly colorectal cancer, these benefits were outweighed by increased risk of heart attacks, stroke, blood clots, breast cancer and perhaps dementia
– a devastating results for postmenopausal women who were encouraged to go on HRT to reduce their risk of heart attacks and strokes

The Nurses’ Health Study (1985), coordinated by Harvard University in Boston, enlisted almost 100,000 nurses to fill out questionnaires mailed to them each year on diet, health status etc. Any reports of illness were confirmed by medical reports.

2. Antioxidants like vitamins E, C and beta carotene (vitamin A) were believed to prevent heart disease

A Cochrane review published this year in JAMA (February 28, 2007;297:842-56) (and The Cochrane Library 2008, Issue 2) concluded from 68 randomised controlled trials involving 232,606 people that they had not found any convincing evidence that antioxidant supplements have beneficial effects in preventing deaths. Separating out 47 trials with low bias (180,938 people) People taking any antioxidant were 5% more likely to die than those who were not. The risk was 4% with vitamin E, 7% with beta carotene and 16% with vitamin A. These were people without nutritional deficiencies.

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How to improve the use of medicines by consumers – a manual

How to improve the use of medicines by consumers [Manual/Handbook] by CHETLEY, Andrew et al, 2007
This manual focuses on selecting, testing, implementing and evaluating interventions to improve
the use of medicines at community level.
http://www.who.int/medicines/publications/WHO_PSM_PAR_2007.2.pdf


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