EVIDENCE BASED MEDICINEGroup 4 (3A)

ACTIVITY 1The Introduction

Question 1What does Evidence Based Medicine (EBM) really

imply?• The most common definition of EBM is taken

from Dr. David Sackett. • EBM is "the conscientious, explicit and judicious

use of current best evidence in making decisions about the care of the individual patient.

• It means integrating individual clinical expertise with the best available external clinical evidence from systematic research." (Sackett D, 1996)– REFERENCE: Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson WS: Evidence based

medicine: what it is and what it isn’t. BMJ 1996; 312:71-2.

• EBM is the integration of: – clinical expertise, – patient values, – the best evidence into the decision making process

for patient care• Clinical expertise refers to the clinician's

cumulated experience, education and clinical skills

• The patient brings to the encounter his or her own personal and unique concerns, expectations, and values

• The best evidence is usually found in clinically relevant research that has been conducted using sound methodology. (Sackett D, 2002)

The Flow

WHAT WAS EBM NOT MEANT TO BE? DISCUSS SOME MISUNDERSTANDING ON EBM

Question 2

• The evidence, by itself, does not make a decision for you, but it can help support the patient care process– The full integration of these three components

into clinical decisions enhances the opportunity for optimal clinical outcomes and quality of life

– The practice of EBM is usually triggered by patient encounters which generate questions about the effects of therapy, the utility of diagnostic tests, the prognosis of diseases, or the etiology of disorders

• EBM's proponents advise that EBM applies to populations but this does and should not preclude doctors from using their personal experience of the patient in front of them and their personal experience from making judgments about how to treat the patient in front of them.

• EBM's function is to inform and not to be a cookbook

• the knowledge gained from clinical research does not directly answer the primary clinical question of what is best for the patient at hand.

• Evidence-based medicine can also give an illusion of practicing "scientific" medicine that is naïve.

• For example, in psychiatry, where knowledge of etiology and pathogenesis of psychopathology is still rudimentary, evidence based medicine for a given diagnosis is claimed to be the gold standard, when the nature of the diagnosis itself is controversial.

• DSM IV & ICD-10 represents agreed upon operational definitions and treatments can be statistically validated for that diagnosis, but advantages over placebo may be unimpressive, given inadequate scientific knowledge.

• Indeed focusing on the treatment of a diagnosis (rather than symptoms) may be the equivalence of blinders, narrowing treatment possibilities

GIVE A BRIEF HISTORICAL PERSPECTIVE ON THE EVOLUTION OF EBM

Question 3

Chronological History of EBM

ACTIVITY 2The Research

• “In the early and mid 1990s, several research report suggests that hormone replacement therapy ( HRT ) were beneficial for post menopausal women . This lead to widespread use of HRT among healthy post menopausal women. Vitamins, in particular vitamins C and E, were also thought to be beneficial for cancer and cardiovascular prevention respectively.”

• QUESTION 1• Look up the main research findings which persuaded

doctors to recommend HRT to post menopausal women and vitamins C and E for cancer and cardiovascular prevention. Summarise the main findings of these research

THE WOMEN'S HEALTH INITIATIVE STUDY

• The WHI was launched in 1991, for 15 years and consisted of a set of clinical trials and an observational study, which together involved 161,808 generally healthy postmenopausal women.

• The clinical trials were designed to test the effects of postmenopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancer.

• The hormone trial had two studies:– Estrogen-plus-progestin study of women with a

uterus (Women with a uterus were given progestin in combination with estrogen, a practice known to prevent endometrial cancer.)

– Estrogen-alone study of women without a uterus. • Both hormone therapy studies, women were randomly

assigned to either the hormone medication being studied or to placebo. Those studies have now ended. The women in these studies are now participating in a follow-up phase, which will last until 2010

Two analyses:• Primary publications

Suggests that risk due to hormones may differ depending on age or years since menopause.

• Secondary analysis Women who begin hormone therapy within 10 years of menopause may have less risk of coronary heart disease (CHD) due to hormone therapy than women farther from menopause.

Other findings:• increased risk in heart disease due to hormone therapy

in older women is primarily in those who also have hot flashes and night sweats. They were also more likely to have risk factors for CHD such as high blood pressure or high blood cholesterol

• Confirmation that hormone therapy increases the risk of stroke not influenced by age or time since menopause

• Even in women within 10 years of menopause, there appears to be an increased risk of breast cancer in women taking estrogen with a progestin

• There was a trend (not statistically significant) towards reduced risk for death associated with hormone use in younger compared to older women.

Refrences :• http://www.nhlbi.nih.gov/whi/• http://www.nih.gov/PHTindex.htm• http://www.nih.gov/news/pr/apr2007/nhlbi-03.htm

ACTIVITY 3The Change

What were the findings that lead to a change in doctor’s attitudes

towards HRT, Vitamin C and E?

From: Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women - Principal Results From the Women's Health Initiative Randomized Controlled Trial Writing Group for the Women's Health Initiative Investigators JAMA. 2002;288:321-333.

Design: A randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.

From: Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women - Principal Results From the Women's Health Initiative Randomized Controlled Trial Writing Group for the Women's Health Initiative Investigators JAMA. 2002;288:321-333.

Design: A randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.

Results • On May 31, 2002, after a mean of 5.2 years of follow-up, the data

and safety monitoring board recommended stopping the trial of estrogen plus progestin vs. placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002.

Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were:• CHD, 1.29 (1.02-1.63) with 286 cases.• Breast cancer, 1.26 (1.00-1.59) with 290 cases.• Stroke, 1.41 (1.07-1.85) with 212 cases.• PE, 2.13 (1.39-3.25) with 101 cases.• Colorectal cancer, 0.63 (0.43-0.92) with 112 cases.• Endometrial cancer, 0.83 (0.47-1.47) with 47 cases.• Hip fracture, 0.66 (0.45-0.98) with 106 cases.• Death due to other causes, 0.92 (0.74-1.14) with 331 cases.

Corresponding HRs (nominal 95% CIs) for composite outcomes were:• 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease).• 1.03 (0.90-1.17) for total cancer.• 0.76 (0.69-0.85) for combined fractures.• 0.98 (0.82-1.18) for total mortality.• 1.15 (1.03-1.28) for the global index.

• Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal

cancers and 5 fewer hip fractures. • The absolute excess risk of events included in the global

index was 19 per 10 000 person-years.

Conclusion• Overall health risks exceeded benefits from use of

combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women.

• All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic

diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.

ResultsThere were the following results found for the use of vitamin C and vitamin E in these doses, various combinations, and populations:

• No decrease risk of death due to cancer.• No decrease of new tumor formation for populations

studied, except for one arm of the ATBC study and one tumor type (AT for prevention of prostate cancer).

• There was No decrease in risk of death for vitamin C in the doses as treatment for advanced cancer

From: Effect of the Supplemental Use of Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cancer Summary by the Agency for Healthcare Research and Quality (AHRQ) Under its Evidence-based Practice Program.38 studies on 23 unique trials

From: Effect of the Supplemental Use of Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cancer Summary by the Agency for Healthcare Research and Quality (AHRQ) Under its Evidence-based Practice Program.38 studies on 23 unique trials

Conclusion• There was No benefit for the development of new colonic

polyps in the doses, populations tested; the combination of vitamins C and E was not clinically superior to placebo in secondary prevention and the combination of vitamins C and E with betacarotene or vitamin A did show a trend favoring a reduction in polyp recurrence but this finding was NOT statistically significant.

• The systematic review of the literature does not support the hypothesis that the use of supplements of vitamins C or E or coenzyme Q10 in the doses tested generally help prevent and/or treat cancer in the populations studied. There were isolated findings of benefit, which require confirmation.

Results• The available scientific studies offer little evidence that

supplementation with vitamin C, vitamin E, or coenzyme Q10 has any benefit on cardiovascular disease prevention or treatment.

• Indeed, for vitamin E and vitamin C there is good evidence that supplementation at the doses tested provides NO benefit, in that large placebo controlled, randomized studies have reported NO benefit in terms of all cause mortality, cardiovascular mortality, myocardial infarction, or blood

lipids.

From: Effect of the Supplemental Use of Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cardiovascular Diseases

Summary by the Agency for Healthcare Research and Quality (AHRQ) Under its Evidence-based Practice Program. 159 reports on 144 unique trials

From: Effect of the Supplemental Use of Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cardiovascular Diseases

Summary by the Agency for Healthcare Research and Quality (AHRQ) Under its Evidence-based Practice Program. 159 reports on 144 unique trials

Conclusion• Isolated examples of possible benefit for vitamin

E or vitamin C supplementation reported for specific outcomes in certain trials failed to be supported by other outcomes in the same trials or be confirmed in other trials. This lack of consistency in the evidence casts doubt on any of the reported associations being causal.

• There is good evidence that vitamin E supplementation has no clinically important effect on lipid levels.

What does all these research conclusions tell us?

• Researches enable us to gauge the usefulness and end-results of a certain product/procedure.

• End-results may differ in that it may be a positive or a negative outcome.

• Encourage newer developments in the medical field an newer ideas to help save lives.

ACTIVITY 4

Trigger

• Doctors and patients are sometimes confused by conflicting research results. This has led some to be cynical about research findings

THINK OF SOME REASONS WHICH MAY MAKE DOCTORS CYNICAL OF RESEARCH FINDINGS

Question 1

1.To gain profit from the drug company which involve in the research even though the research findings are not similar to the reported one.

2.To find fame for 'claimed' successful research3.Get the chance to be promoted to higher

rank/level4.To prove that they are capable to do a

research finding just like their colleagues

SUGGEST WAYS AND MEANS OF REASSURING DOCTORS AND THE PUBLIC THAT RESEARCH FINDINGS ARE INDISPENSIBLE IN THE PROGRESS OF MEDICAL KNOWLEDGE

Question 2

1. Make an act or some legislation towards implementation of EBM in medical practice

2. Clear all the conflict of the clinical results3. Do a campaign towards EBM to the community4. Show some benefit when using the EBM in

medical practice5. Educate the public of the importance of

research findings via posters pasted on all hospital and clinic

6. Build some organization to move the EBM (eg: The Cochrane Collaboration is a major force in the EBM movement)

Benefit of EBM

• EBM has three main advantages: 1. It offers the surest and most objective way to

determine and maintain consistently high quality and safety standards in medical practice;

2. It can help speed up the process of transferring clinical research findings into practice;

3. It has the potential to reduce health-care costs significantly.

ACTIVITY 5Problems?

Trigger

• About 10 years ago, the Times magazine ran a issue which highlighted misconduct in medical research. That particular issue of the Times magazine was dedicated to telling the world that research conducted in medicine were questionable, leading to erroneous conclusions being made and potentially subjecting the public to harm.

DISCUSS THE CONCERNS MENTIONED ABOVE AND SUGGEST CORRECTIVE STEPS WHICH WILL REASSURE THE PUBLIC THAT SUCH CONCERN IS BEING ADDRESSED BY THE MEDICAL RESEARCH COMMUNITY

Question 1

• Among the medical misconducts discussed were the falsifying of scientific data especially when medical researchers are left to internal inquiries and self regulation.

• When medical researches are funded by drug companies when vested interest of promoting their product, it is important that there are external agencies to regulate the clinical trials conducted.

• It is the duty of the scientific community is to verify the integrity of other articles published by the author of a fraudulent article.

BESIDES THE PUBLIC, WHO ELSE ARE THE STAKE HOLDERS IN ENSURING RESEARCH DONE IS OF THE HIGHEST STANDARD; ETHICALLY AND SCIENTIFICALLY

Question 2

• Besides the public, governmental institutions and the scientific community especially medical professionals are stake holders in ensuring research which are done is of the highest standard; ethically and scientifically

WHAT SHOULD BE THE ROLES AND RESPONSIBILITIES OF VARIOUS STAKE HOLDERS

Question 3

• Governmental institutions should have the authority to investigate and punish guilty scientists and requires that research institutions investigate alleged fraud to maintain the integrity of scientific literature.

• Scientific community should warn medical professionals to ignore articles containing faked data and must try to prevent inadvertent citation of it.

• Medical professionals should be aware of falsified clinical data and keep themselves up to date with these fraudulent medical researches.