One should be able to read the evidence when presented in front of him/her.

**Self limiting disease**:

A person with a disease will get cured once the disease has run its course of action. But the medical treatment can shorten the time to bring the disease to an end more quickly.

**p-value and Confidence Interval**

1. P-value stands for probability of error. It’s value can vary from 0 to 1. e.g. p=0.04 means 0.04*100 = 4% probability that a result could have occurred by chance.

2. The amount of evidence required to accept that an event is unlikely to have arisen by chance is known as **threshold/critical p-value/significance level (called alpha). This value is set before you do the experiment.**

3. The statistical significance of a result tells us something about the degree to which the result is “true”. Statistical significance can be considered to be the confidence one has in a given result being non-random. Confidence is a proportional to square-root of sample size.

4. Confidence Interval (CI) indicates how reliable the results are.

a. If the P-value computed while performing the experiment < threshold/critical P-value (called alpha) set (normally 0.05) before you do the experiment, the difference is “statistically significant”. That means smaller the p-value better it is.

b. If the P value > threshold, the difference is “not statistically significant”.

**Confidence level:** Generally set at 95%. If confidence level is 95%, then critical p-value is calculated as 100-95= 5% i.e. 0.05

**Power Analysis**

It reveals the appropriate/minimum sample size required to achieve expected effect

for a given confidence level.

A sample size less than the appropriate will have the probability of false null

hypothesis/type-2 error.

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**odds-ratio**

It is the ratio of the chance that something will happen to the chance that it will not happen. So mathematically, odds ratio = chance/ (1-chance)

**Likelihood ratio**:

It is a ratio of True Positives to False Positives,

ex. the prevalence of symptom in the population cured by certain medicine divided by the prevalence of the symptom in the rest of the treated population

**Bias**

1. Error is of two types: random and systematic error

2. Unlike random error, systematic error does not get reduced as sample size (n) increases.

3. Bias is a systematic error i.e. the difference between study findings/outcomes and the truth.

4. Broadly, bias is of two types: Selection bias and information/observation bias.

5. Selection bias is due to wrong selection of samples (subjects included for participation in study)

6. Information bias is due to wrong methods by which information is collected from the participants who met inclusion criterion.

7. **Publication bias: **The tendency for studies with a positive result to be published more readily than those which are negative or inconclusive.

8. **Confirmation bias** is a bias on the part of researcher to favour results that confirms their hypothesis

9. A bias can switch the result of an RCT from positive to negative or viceversa. 10. It’s impossible to eliminate the bias completely. We can only reduce the bias.

11. As bias approaches towards zero, ‘**generalisation**‘ suffers that means you can’t generalise (read extend) inference/results of your study (based on sample data) to reference population which renders the study less useful. So there’s a tradeoff between the amount of bias accepted and generalisation capability of your study.

12. BMJ 2003: “Conclusion: Systematic bias favours products which are made by the company funding the research” http://www.bmj.com/content/326/7400/1167

13. Methods to reduce bias: blinding, randomisation, prospective study instead of retrospective studies.

**Double-blind: **

Neither the subject nor the person administering treatment knows which treatment any particular subject is receiving

**Efficacy of Treatment**

Efficacy is the extent to which the medical treatment/intervention has therapeutic effect under ideal test conditions

1. **Specific (pharmacological/physiological) effects**: patients getting better because of the therapeutic effects of the medical treatment/intervention.

2. **Non-specific (psychological/placebo) effects**:The body’s healing response is activated

a. By the patient’s anticipation of the cure because they expect to get better after visiting the doctor.

b. By the reassurance given by the doctor that he will be cured (empathy)

c. When given a medicine but not told that it is actually a placebo. Placebo also has a therapeutic value if the patient is not told that he is being given a placebo. The placebos have surprisingly positive clinical effects on patient’s medical condition because it involves the secretion of dopamine.

3. Any treatment is effective because of the both specific and non-specific effects. In fact non-specific effects are larger than specific effects. The drawback of RCT is that is designed to measure only specific effects. **Placebo-controlled** RCT measures if the effect is due to placebo or not.

4. **Randomisation**: Divide the patients/group (sample size) randomly into a treatment group that receives the treatment, and a control group that does not.

5. The treatment would then be judged effective only if the treatment group improves more than the control group.by significant amount.

**Effectiveness**

Effectiveness is the extent to which the medical treatment/intervention has therapeutic effect under real-world settings.

Which one is more important: Efficacy or Effectiveness?

and if you feel both are equally important, then which one should first be seeked: Efficacy or Effectiveness?

**Levels of Evidence** [2]

Level I meta-analyses and/or systematic reviews

Level IIa multiple RCT

Level IIb some RCT

Level IIIa multiple cohort studies

Level IIIb some cohort studies

Level IV opinion of experts

**Placebo**

An inactive dummy/inert pill (substance such as lactose/saline which do not alter the disease condition) prescribed to the patient for the following purposes

1. To enhance the non-specific effects of the treatment. Placebo has a therapeutic value if the patient is not told that he is being given a placebo.

2. The doctor does not want to disturb the course of action of previously prescribed medicine till it completes its own run.

So administer a placebo during the intermittent period of two far apart doses of

medicine in time serves both the purposes

3. Given as control treatment in placebo-controlled trials during medical research

**Nocebo Effect**: The adverse effects of placebo

**Null Hypothesis**

1. The null hypothesis assumes that any kind of significance in a set of data is due to chance.

2. Null hypothesis is presume to be true until statistical evidence nullifies it.

3. When the null hypothesis is rejected, the result is said to be statistically significant.

**Regression towards the mean**

Explained with he help of an example [1]

Do a test on a bunch of subjects. Rank the subjects by their score and select the bottom half of the bunch. Retest the bottom half. The average score of the bottom half will probably improve somewhat on retest. Similarly, the average score of the top half will probably drop somewhat on retest. These changes in performance are called regression towards the mean. The name refers to a tendency for subjects who score below average on a test to do better next time, and for those who score above average to do worse.

The group you select doesn’t have to be the bottom or top half, and the test doesn’t have to be the first one. Any group or even any subject you choose with an average score below or above the mean of all the subjects in a given test will probably move (regress) noticeably closer to the mean in another test. ’Regression towards the mean’ means ‘averaging out’

**Biological Model**:

Model of an organism to understand a particular biological phenomena. They are generally in-vivo models. They are of two types: Pharmacological and Toxicological model

**in vitro**

in-vitro studies are those that are conducted on components (instead of whole) isolated from a living organism such as cells, components of cells such as ribosomes or mitochondria, extracts of cells such as reticulocyte or cell molecules such as acids or proteins or tissues. Vitro means glass. The invitro studies are conducted in test tubes and culture dish

**Meta-analysis**

It is a statistical method of combining results from multiple randomised controlled trials in the form of a weighted average (some studies carries more weight than others) as an output. It helps in reducing information overload, find publication bias, if any and may explain heterogeneity between the results of individual studies.

**Systematic Review**

It is synthesis of the results of several studies (including conflicting studies) so as to assess the strength of the evidence.A review is termed systematic if it is based on clearly formulated peer-reviewed protocols (in advance) such as research question, clear inclusion/exclusion criterion, explicit search strategy, etc and employs the same level of scientific rigour as should be used to produce that research evidence in the first place. A systematic review can be independently replicated.

**Outcome Research**:

It focuses on

1. The treatment improved quality of life or not

2. Safety Profile of medicines used in treatment

**Repeatability and Reproducibility**

1. During a test/experiment, let’s say you do certain measurement. When the test is repeated (re-test/replicate) in same conditions [same observer (the person who is conducting the test), same laboratory and same equipment), three conditions arises

2. If you get the same measurement in same conditions, we say it's 100% repeatable.

3. If the variation in measurement is with in the set tolerance (agreed difference), we say, the measurement is repeatable otherwise variable (variability)

4. If the re-test is conducted in same test conditions but in different locations (multi-centre) by different people (independent) and you get the same results (within the set tolerance), we say the test is reproducible

**Research Fundamentals**

1. Aim/Objectives of research

2. research design: research methods

3. sampling: selection of participants

4. Ethical issues

5. Taking care of bias

6. Data Collection

7. Data Analysis

8. Research Findings

9. How valuable is the research?: Contribution of study

**Ethical issues in Research**

1. Objectives and methods of research explained to participants

2. Informed consent by participants

3. Confidentiality of information

4. what to do with the outcome of study

**Semmelweis reflex** is a tendency to reject new evidence or knowledge because it contradicts established beliefs or paradigms.

**References**

[1] http://www.sportsci.org/resource/stats/regmean.html

[2] Michel van Wassenhoven ECH Publication, LMHI 2008

Science, Scientism & Scientific

It is normal to live in the knowledge that the circle of knowledge that we may have, is inscribed by a circumference of the darkness of the unknown, that is, of unknown proportions. Within it lays the understanding of homoeopathy. It should not be surmised that we have at present reached the limit of the knowable. Because the unknown and unknowable is preponderant beyond compare, it must certainly be determinant and control the sphere of finite or so-called knowledge. The reason is it “so-called” is because it can only be apparent or incomplete knowledge, for the unknown lies not only outside but also within everything. Inside our homoeopathic remedies lies something unknown, but from what has been discovered so far, it is certainly not unknowable. Thus the practical application through inference – which is a valid way to come to knowledge – shows that the inference is right, backed up by NMR, RLS, piezo-electric values and other methods of determining whether something is there or whether nothing is there. The conclusion is that something is there, although we cannot see it.

This is our position. One may like to think that nothing is superior to oneself. But this is certainly mere egotism. Our honest position is that we are finite beings trying to maintain our existence, know our real purpose in life, and to find fulfillment, which is the definite discovery of the homoeopathic mechanism in objective, scientific terms. We have come a long way, but admittedly, we have not yet been able to explain to everyone’s satisfaction. Philosophy teaches us to acknowledge both the finite and infinite worlds that constitute reality. It is really a matter of humility and sanity. This is the beginning. We already have a relationship with the finite reality. What is missing for many is their relation with the infinite that is above and beyond them. This kind of scientific knowledge will be complete real knowledge. We are like Venetian blinds and curiosity is our Columbus. And that is the message that we are trying to deliver through this post.

So far as “evidence base” is concerned, it is still not a scientifically validated ideology that has always been observed. The evidence is lacking, and sorely, as the latest JAMA and BMJ state. BMJ goes so far as to say none can be trusted. Where then is the evidence base? It is imaginary and visible on the numbers on a machine, although the machine has nothing to do with the diseased man. Scientists continue trying to impose their idea on Nature, rather than observing Nature and letting her present her evidence to us. We don’t observe suppression. We are blind to the facts. The facts are that our society is a society of suppression. It begins with ideology, regardless whether this is religious or atheist. Then follows education, which is meant to make you a memory bank, engaged in classification, enumeration and calculation. We have effectively been reduced to bookkeepers, if we succumb to the demand for numbers as a sign of proof.

We shall provide an example that shows the fallacy of this type of reasoning. If we look at the elections and we see a voter turnout of 30%, we note that their affiliations for leftwing or rightwing politics is split approximately down the middle. 70% have declared not to agree with the votes and the voted for and so these need do nothing but go home. Yet nobody will accept this as the outcome, because not voting is declared to have no voice. From an objective point of view, the nonvoters are right – the government has been rejected by 70%. That would be real democracy, when all the votes – also the non-vote of “no confidence” – would be counted. That is scientific, because it does not leave out uncomfortable data. Nonetheless, we have excluded the non-voter, although as a sign of proof for “no confidence” they have easily carried the day. The numbers can be easily twisted and turned to manipulate what one wanted to say. I bet the bookkeepers are past masters and I wait for someone to come and juggle the numbers.

We don’t observe anything other than similar either.

Like produces like. Dogs come from dogs, humans from humans, etc.

Like attracts like. We don’t see that humans are attracted to monkeys, apart from a few exceptions and that in a very limited way.

Like imitates like. We don’t see the donkey playing lion.

Like cures like, as homoeopathy always proves.

Like neutralises like. The antidote will always neutralise the effect of the previous remedy. An acid neutralises and acid.

So rather than scientists imposing their idea on the nature of our potencies, we should let the nature of potencies determine which is right. To try to fit Nature into some Procrustean bed made by the finite brains of scientists, is not science and will not lead to any progress in science. To go back into “evidence based” is to go back into deep dreams that ultimately lead nowhere, as all dreams do. To declare placebo to be the origin of observed phenomena is equally of an unreal nature and leads not to any real understanding. Now at this juncture of our medical scientific revolution, it would be a good time to stop wasting time and daydreaming and go in the direction of some real science. This is my humble opinion.

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I have visited your webpage”EVIDANCE BASED HOMOEOPATHY” NANO MEDICINE & was very much impressed about your research in HOMOEOPATHY.No doubt Dr. Hahnemann was the first physician/nano/quantum mechanics scientist to administer medicines in the form of uld/ultra low doses in the form of nano atoms & its excited levels.I & my wife are doing fundamental research & practicing Homoeopathy at KOLHAPUR/MAHARASHTRA/INDIA since last 27 years.Very soon in the month of August 2013 we are going to visit Grmany.

Many patients of IHD,HEMIPLEGIA,AIDS,AZOOSPERMIA,ANOVULATOEY CYCLES have been benifited with CLASSICAL HOMOEOPATHIC MEDICINES.kINDLY INFORM ME REGARDING YOUR LATEST RESEARCH IN HOMOEOPATHY.

DR VINAAYKUMAR & DR MRS SUNITII V.GOPALAKR.

22.7.13