Research types ksr

Research Types in Ayurveda

Research is a search for Knowledge, at the appraisal, as less as people understand they

reciprocate appreciation pretended projection as more as they understood.

-

Dr KSR Prasad

Lecture delivered at MGACH&RC, Wardha

Dr. K. Shiva Rama

Prasad, at http://www.technoayurveda.com/

Dr. K. Shiva Rama



Research is balancing Science, Economy, Safety,Quality &Efficacy for attaining new knowledge


Dr. K. Shiva Rama


Dr. K. Shiva Rama



Dr. K. Shiva Rama



From the word “I can not”

to . . .

Dr. K. Shiva Rama



Each and every episode we encounter in the profession is tackled with challenge –

even -

Dr. K. Shiva Rama



Design the “challenge”

to a project

Dr. K. Shiva Rama



Dr. K. Shiva Rama



Dr. K. Shiva Rama



Whether the Research is “CHOICE” or “CHANCE”

Dr. K. Shiva Rama



Deploy argument to stop Struggle between Types / Designs / Phases

Dr. K. Shiva Rama



Research Methodology and Statistics Evident in Ayurveda Treatises –

Dr. Asmita

Wele

•

Basic level research is defined as a process to find the truth -

operational level

steps involved to find the truth are ––

Clinical research

–

Drug research–

Literary research

–

Epidemiological–

Fundamental

www.ayusoft.cdac.in/pshome/apps/en/src/Articles/Research/Research_Methodology_and_Statistics_Evident_in_Ayurveda.htm

Mile stones of Initiation for regulation •

Drugs & Cosmetics Act 1940 and the Rules. National policy on traditional medicine in India updated 1964,1970, 1982

•

In 1959, the Govt. of India amended the Drugs and Cosmetics Act to include drugs which are derived from traditional Indian medicine.

•

The Indian Medicine Central Council Act, 1970•

CCRAS, established for research in 1978 by GOI, coordinates and promotes research in the fields of Ayurveda medicine

•

In 1993, the guidelines for the safety and efficacy of herbal medicines developed by an expert committee

•

AYUSH regulation-2005

Dr. K. Shiva Rama



WHO initiatives•

Since 1991, WHO –

–

Guidelines for the assessment of herbal medicines; –

Research guidelines for evaluating the safety

–

Efficacy of herbal medicines; and –

Guidelines for clinical research on acupuncture.

•

In 1997, WHO in support of ––

National Center of Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD, USA, a WHO informal discussion developed –

•

draft guidelines for methodology on research and evaluation of traditional medicine.

Dr. K. Shiva Rama



Assessment of Ayur-medicine in clinical research 1.

Evaluate traditional medicine in its own theoretical framework (Tridosha, Sapta dhatu, Dasa vidha Pariksya etc)

2.

Evaluate traditional medicine in the theoretical framework of conventional medicine (e.g. mechanistic studies);

3.

Compare the efficacy of Ayurveda with different systems of traditional medicine and/or conventional medicine;

4.

Compare the efficacy of different practices within Ayurveda.

5.

Ayurveda drugs: Single herb / mineral / animal product / Poly herbal / Folk medicine

Dr. K. Shiva Rama



Clinical trial -

Regulation•

Central Drugs Standard control Organization issued GCP for clinical research in India.

1.No Phase I study is required.2.Neither would any toxicity study be needed for phase

II trial unless there are reports suggesting toxicity or when the herbal preparation is to be used for more than 3 months.

3.Treated as a new substance or new chemical entity (NCE) and the same type of acute, sub-acute and chronic toxicity data will have to be generated as required by the regulatory authority before it is cleared for clinical evaluation.

Dr. K. Shiva Rama



Clinical trial for Ayurveda drug must be carried out under conditions which ensure adequate safety for the

subjects and registered in www.ctri.in

Ayurveda Clinical trial Registration

Dr. K. Shiva Rama



What research is necessary?•

A research which have evidence

•

Which is ––

Feasible,

–

Clear–

Significant

–

Ethical

Dr. K. Shiva Rama



Dr. K. Shiva Rama



Level Therapy Prognosis Diagnosis Aetiology

I Systematic Review

Systematic Review

Systematic Review

Systematic Review

II RCT Inception cohort

Cross-sectional(consecutive)

Prospective cohort

III Non-

Randomised experimental

Untreated control patients in RCT

Cross-sectional (non-

consecutive)

Retrospective cohort

Comparative with concurrent control group

Retrospective cohort

Diagnostic case-control

Case-control / Ecological

IV Case series Cohort patients different disease

Case series Cross-

sectional

Questions to ask at Research •

What is study about?

•

What are the goals?•

Study sponsor?

•

Participant input into protocols? •

Inclusion criteria?

•

Benefits & risks•

Is there an incentive? (positive motivational influence / payment)

•

How protected from harm?•

What is required: # study visit & what occurs?

•

What happens after study is over?•

How results will be disseminated?

Dr. K. Shiva Rama



Nine Mistakes to Avoid1. leading questions2. questions that invite the social

desirability bias3. double-barreled questions4. long questions5. negations6. irrelevant questions7. poorly worded response options8. big words9. ambiguous words & phrases

Dr. K. Shiva Rama



What makes a good question? FINER

criteria

Feasible (answerable with a robust method)

InterestingNovelEthicalRelevant

Dr. K. Shiva Rama



Exactly what are you planning to do?

PICO

P

-

who are the patients or what’s the problem?I

-

what is the intervention or exposure?

C

–

what is the comparison group?O

-

what is the outcome or endpoint?

Dr. K. Shiva Rama



Presenter

Presentation Notes

Richardson et al. The well-built clinical question: a key to evidence-based decisions. ACP Journal Club 1995;A-12 Counsell C. Formulating questions and locating primary studies for inclusion in systematic reviews. Ann Intern Med 1997;127:380-7 What’s your question about? cause/aetiology [cohort, case-control] impact of an intervention eg treatment or health service [RCT] prognosis [cohort] harm [cohort, case-control] diagnosis [cross-sectional, case-control] economics [cost-effectiveness analysis, etc]

More on PICOPatients•

disease or condition•

stage, severity•

demographic characteristics (age, gender, etc.)Intervention•

type of intervention or exposure•

dose, duration, timing, route, etc.Comparison•

risk or treatment•

placebo or other active treatmentOutcome•

frequency, risk, benefit, harm•

dichotomous or continuous•

type: mortality, morbidity, quality of life, etc.

Dr. K. Shiva Rama



Presenter

Presentation Notes

Credit – presentation on Formulating the Review Question �& Writing a Protocol [for a systematic review] by Madhukar Pai, MD Systematic Reviews Group Division of Epidemiology University of California, Berkeley [email protected]

Dr. K. Shiva Rama



Dr. K. Shiva Rama



Level Vs Quality of Evidence

Dr. K. Shiva Rama



Two sets of pyramidal explanation

Dr. K. Shiva Rama



Dr. K. Shiva Rama



Research questionsdetermine problem

(case reports/case-series, ecological/cross-sectional studies)

design interventions(randomized controlled trials)

find potential causes(case-control/cohort studies)implement activities

(surveillance studies, meta-analyses)

Dr. K. Shiva Rama



Trial Typology

Are you going to observe or experiment?Observational –

cross sectional, case series, case-control studies,cohort studies•

identify participants•

observe and record characteristics•

look for associations

Experimental –

before and after studies, comparative trials(controlled or head to head), randomised trials (ditto)•

identify participants•

place in common context•

intervene•

observe/evaluate effects of intervention

Dr. K. Shiva Rama



Presenter

Presentation Notes

experimental study researcher manipulates exposure by allocating participants to intervention or exposure group follow up under carefully controlled conditions. Controlled trials, when randomised and blinded, can control for biases analytic observational study case control, cohort, some cross-sectional studies measure exposure in the groups match groups of participants assess associations between exposures and outcomes Centre for Evidence Based Medicine, Oxford, UK cebm.net

Study designs

Population (P) Outcomes (O) Interventions (I) or Exposures (E) Centre for Evidence Based Medicine, Oxford, UK www.cebm.net

Dr. K. Shiva Rama



Presenter

Presentation Notes

From http://www.cebm.net/index.aspx?o=1039 Doesn’t include before and after studies descriptive studies case report, case series, qualitative study, cross sectional survey show what’s happening in a population and in subgroups analytic studies examine effect of intervention (I)/exposure (E) on outcome (O) compare frequency of outcomes in a comparison (C) group with frequency in intervention or exposed group to quantify effect may be experimental or observational Centre for Evidence Based Medicine, Oxford, UK cebm.net Prospective A prospective study watches for outcomes, such as the development of a disease, during the study period and relates this to other factors such as suspected risk or protection factor(s). The study usually involves taking a cohort of subjects and watching them over a long period. The outcome of interest should be common; otherwise, the number of outcomes observed will be too small to be statistically meaningful (indistinguishable from those that may have arisen by chance). All efforts should be made to avoid sources of bias such as the loss of individuals to follow up during the study. Prospective studies usually have fewer potential sources of bias and confounding than retrospective studies. Retrospective A retrospective study looks backwards and examines exposures to suspected risk or protection factors in relation to an outcome that is established at the start of the study. Many valuable case-control studies, such as Lane and Claypon's 1926 investigation of risk factors for breast cancer, were retrospective investigations. Most sources of error due to confounding and bias are more common in retrospective studies than in prospective studies. For this reason, retrospective investigations are often criticised. If the outcome of interest is uncommon, however, the size of prospective investigation required to estimate relative risk is often too large to be feasible. In retrospective studies the odds ratio provides an estimate of relative risk. You should take special care to avoid sources of bias and confounding in retrospective studies. http://www.statsdirect.com/help/basics/prospective.htm

Describe patients’

characteristics, and may generate ideas for future studies

Case Report Series

Dr. K. Shiva Rama



Randomized Controlled TrialPopulation

Sample

BaselineAssessment

Meet InclusionCriteria?

Follow-upassessments

•Typical RCT randomises two (or more) groups of patients to different treatments

Dr. K. Shiva Rama



Population

sample

Group of interest(e.g. smokers)

Comparison Groupof interest

(e.g. non-smokers)

Compute prevalenceof stroke in smokers

Compute prevalenceof stroke in non-smokers

Comparegroups

Present

Starting point

•A cross-sectional study is a single “snapshot”

in time•We can only study current risk factors and diseases (prevalence)

Cross-sectional study

Dr. K. Shiva Rama



Population of diseased individuals

Sample of diseased individuals

ExposureHistory Starting pointPast

•Case-control studies examine the association of disease with past exposure (s)

Population of non-diseased individuals

Sample of non-diseased individuals

Case-control study

Dr. K. Shiva Rama



Population of diseasefree individuals

Sample

Starting point Future

• Selected group of disease-free people who are classified according to a specific exposure.•Observed over time to see who develops the disease or outcomes (s) of interest.•Can measure incidence (new cases of disease) and thus risk

Cohort study

Dr. K. Shiva Rama



Three Main Types: Classifications of Research Studies

Observational Studies:Observational Studies:•

Groups are studied & contrasts made between groups•

The observed data collected are analyzedAnalytic Studies:Analytic Studies:•

Also called Experimental•

Study the impact of a certain therapy•

Ultimately the investigator controls factor being studiedClinical Trial:Clinical Trial:•

Considered the “true”

experimental study•

“Gold Standard”

of clinical research•

Often a prospective study that compares the effect and value of an intervention against a control in human subjects

Dr. K. Shiva Rama



Phases of Clinical Trials••

Phase I:Phase I:

Small group [20-80] for 1st time to

evaluate safety, determine safe dosage range & identify SE

••

Phase II:Phase II:

Rx/tx given to larger group [100-300] to confirm effectiveness, monitor SE, & further evaluate safety

Dr. K. Shiva Rama



Phases of Clinical Trials (cont.)••

Phase III:Phase III:

Rx/tx

given to even larger group

[1,000-3,000] to fulfill all of Phase II objectives & compare it to other commonly used txs

& collect data that will allow it to

be used safely••

Phase IV:Phase IV:

Done after rx/tx

has been

marketed -

studies continue to test rx/tx

to collect data about effects in various populations & SE from long term use.

Dr. K. Shiva Rama



Reporting statementsCONSORT for randomised controlled trials STARD for diagnostic accuracy studies STROBE for observational studies PRISMA for systematic reviews of trialsMOOSE for meta-analyses of observational

studies EQUATOR network

equator-network.org/resource-centre/library-of-health-research reporting/

Dr. K. Shiva Rama



Level of significance

•

Relies on α

error or type I error. The maximum level of α

has been arbitrarily

set to 5% or 0.05. •

Alpha error can be minimized to 0.01 or even 0.001 but this consequently increases the sample size. –

Thus, sample size is inversely related to the level of α

error.

Dr. K. Shiva Rama



Pros and cons of the RCTAn experimental comparison study where participants are

allocated to Treatment / intervention or control / placebo groups using a random mechanism is RCT; Best for studying the effect of an intervention.

Advantages: –

unbiased distribution of confounders –

blinding more likely –

randomisation facilitates statistical analysisDisadvantages: –

expensive: time and money–

volunteer bias –

ethically problematic at times

Dr. K. Shiva Rama



Presenter

Presentation Notes

Study designs Centre for Evidence Based Medicine, Oxford http://www.cebm.net/index.aspx?o=1039

Dr. K. Shiva Rama



Summary •

Research is a Choice

but not Chance•

Innovation, Creativity, Attitude

and utilizing opportunities

makes researcher to reach goal •

Ayurveda did scientific research in the past•

Good research require to follow FINER & PICO•

Type of research adaptation based on the Research question

•

Research quality depends upon the level and Evidence•

Fundamentally types are –

Observational, Analytical & Clinical

•

Research phases 1 to 4

represent the connection with the concerns

•

All researches should have proper registration

and reporting

•

Submitting proper analysis

of non fabricated with good level of significance

is the responsibility of researcher

Dr. K. Shiva Rama



Dr. K. Shiva Rama



1. Dr. Rasha Salama, Conducting Research, PhD. Community Medicine

2. Sara Back, NP, Understanding Clinical Trials, Bronx-Lebanon Hospital Center

3. Dr Rafael Perera, Study design and Levels of Evidence, Director of Research Methods, Center for Evidence based Medicine, oxford University

4. Dr Ashok Kumar Panda, Regulation of Clinical trial in Ayurveda, Regulation of Clinical trial in Ayurveda, Officer In charge, Ayurveda Regional Research Institute, Gangtok,Sikkim, An Unit of Central Council for Research in Ayurveda, Department Of AYUSH, Government of India

5. Dr Trish Groves, Different types of clinical evidence and study design Deputy editor, BMJ, [email protected]

6. www.ayusoft.cdac.in/pshome/apps/en/src/Articles/Research/Researc h_Methodology_and_Statistics_Evident_in_Ayurveda.htm

Acknowledgements of Citations:

Dedicated to Nitin

R ChoudaryPanchakarma

Massager who disappeared in

Road mishapOn 18-01-2014

mailto:[email protected]

Health & Medicine

Research types ksr