study design: the blueprint for success tharyan.pdf · prathap tharyan md, mrcpsych. professor of...

IASCT: Clinical Trial Interfaces 2011; Mumbai

Study Design: The Blueprint for success

Prathap Tharyan MD, MRCPsych

Professor of Psychiatry & Associate Director, CMC Vellore

Director, South Asian Cochrane Network & Centre

Prof BV Moses & ICMR Centre for Advanced Research & Training in

Evidence‐Informed Healthcare

Christian Medical College, Vellore

IASCT Clinical Trial Interfaces 2011; Mumbai

Don’t Just Do It

Do It RightBecause it matters……

If you want to conduct research……


Who needs reliable evidence?

•

Health Professionals at all levels, Health Researchers,

Health Policy Makers, Care Givers and Patients.

EVERYBODY


THIS TALK IS DEDICATED TO ALL OUR MOTHERS


WHAT ARE WE TRYING TO AVOID?


Getting the evidence right: What Is The Truth Here? Look out for my new book, “7 habits of highly successful

and popular people who are

also sensitive boyfriends. ”Biased publications: Cost?


He doesn’t really know what I

want….All he thinks of is his book..His friend is so much more

sensitive to my needs

Confound it!What will they both

do when they find

out I’m gay?


Getting the evidence right: the effects of chance

What are the chances

of this happening?Is this a coincidence?Does it happen

everyday?Or is this an Al Qaeda

plot?

Surfers rule

Dolphins rule


Threats to Internal Validity

•Any

factor

or

process

that

tends

to

deviate

the

results

or

conclusions of a trial systematically away from the truth•Deviation

in

results

can

occur

due

to

systematic

(bias)

or

random errors (chance)•Random errors reduce with increase in sample size; detected

by p values•Bias

can

result

in

overestimates

or

underestimates

of

the

results of a trial (cannot be detected by p values)•Bias

can

occur

due

to

voluntary

or

involuntary

reasons

(not

the same as fraud)


The Gold Standard for assessing

the evidence of the efficacy of interventions

Most prone to bias

A study design that minimizes bias, confounding and the play of

chance

Least biased

IASCT Clinical Trial Interfaces 2011; MumbaiPLOS Medicine August 2005

“In a chase for statistical significance”


The use of

many small randomized trials with

clinically non‐relevant outcomes,

improper interpretation of statistical significance,

manipulated study design,

biased selection of study populations,

short follow‐up, and

selective and distorted reporting of results

has built and nourished a seemingly evidence‐based myth of

antidepressant effectiveness

Philosophy, Ethics, and Humanities in Medicine 2008, 3:14 doi:10.1186/1747‐5341‐3‐14


Getting the evidence straight requires a special effort

Needs a systematic review“A review in which bias has been reduced by the systematic

identification,

critical

appraisal,

and,

if

relevant,

statistical

aggregation

(meta‐analysis)

of

all

relevant

studies

on

a

specific

topic

according

to

a

predetermined

and explicit method.”

Modified from Moher

et al Lancet 1999


Getting the evidence straight

What is needed?

•

Ensure all relevant research is considered

•

Critically appraise research for quality (risk of bias) and applicability

•

Synthesize research findings using appropriate methods


GRADE separates

The overall quality of the evidence

and confidence in the resultStrength of the recommendations

•

Strong recommendations:

most informed patients would

choose the recommended

management

•

Weak recommendations:

patients’

choices will vary

according to their values and

preferences

Grading of Recommendations: Assessment, Development and Evaluation

http://www.gradeworkinggroup.org

http://www.gradeworkinggroup.org/


levels of ‘Quality’ (or confidence in the effect estimate)

•

4 = High

•

3 = Moderate

•

2 = Low

•

1 = Very low

Further research is very unlikely to change our confidence in the estimate of effect

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate

We are very uncertain about the estimate


Grading of Recommendations Assessment,

Development and Evaluation

5 factors to consider• Study Limitations • Indirectness • Inconsistency • Imprecision • Other

Were the studies free of the risk of bias?Where; in whom; and how were the trials done?Is there unexplained heterogeneity?Is the result statistically and clinically important?Publication Bias? Conflicts of interest? Design

specific issues: cross-over trials etc

Grading of Recommendations Assessment,

Development and Evaluation


5 criteria• Limitations (of study design) No serious limitations• Inconsistency (between results) Serious inconsistency (-1)• Indirectness (of evidence) Very serious indirectness (-2)• Imprecision (of measure of effect)• Other (publication bias)

1 Downgraded for serious inconsistency because……….2 Downgraded for very serious indirectness because…….

Quality of Evidence = VERY LOW


The GRADE approach for guideline panels

• Decide on the overall quality of evidence across

outcomes.

• Include judgments about the underlying values and

preferences of management options & outcomes.

• Decide on the balance of desirable and undesirable

effects.

• Decide on the balance of net benefits and cost.

• Grade the strength of recommendation.

• Formulate a recommendation.

• Implement and evaluate.


The single best source of reliable and timely evidence

www.thecochranelibrary.com

Free to all in India thanks to ICMR


www.cochrane.org

•Reliable•Independent•Timely


EVIDENCE BASED MEDICINE

•

The integration of research

evidence, clinical expertise

and patient values

(Sackett

et al, 2000)

Evidence‐Based Medicine Working Group: Evidence‐based medicine. A new

approach to teaching the practice of medicine. JAMA. 1992;268: 2420‐5

http://www.cebm.utoronto.ca/

Is the Evidence Valid?


Addressing the gaps between evidence and practice

Practice

Research

Evidenc

e

Getting the evidence straight Getting the evidence used

Glasziou

P, Haynes B. ACP J Club. 2005

“Seeing through a dark glass dimly”

Presenter

Presentation Notes

We have remarkably little knowledge about what works for getting evidence to practice


Science and ethics are inseparable in research

•

Research

that

does

not

yield

valid

results

is unethical

•

Research, even if valid, that

does not

follow ethical norms is in‐excusable

•

Invalid and unethical research cause harms:•

from wrong evaluations or estimations;

•

ineffective or harmful treatments;

•

denial of effective interventions and

•

betrayal

of

the

trust of research

participants

and

users

of healthcare


The current status of medical research

•

Not all research is meant to improve the lives of patients

•

Not all research is conducted using methods that eliminate

bias and the effects of confounders and hence provide

reliable results

•

Not all research is actually needed

•

Not all research that reports favourable

results actually has

favourable

results

•

Not all reported research reflects all research that has

been conducted

•

Not all clinical guideline developers understand or use

evidence

•

Most clinicians believe what they read


Science & Ethics as it is today

Research SocietyEthical

oversight

Presenter

Presentation Notes

Insert a picture illustrating a season in your country.


Science & Ethics as it should be

ResponsibleResearch

Responsive Society

Ethical oversight

Presenter

Presentation Notes

Insert a picture illustrating a season in your country.


What contributes to ethical and valid research?


AREAS OF CONCERN WITH CLINICAL TRIALS

Industry Trials

Investigator initiated trials


Industry trials

•

Social relevance vs. stock market relevance•

Patent expiring soon‐

replace with “me too”

drug

•

Disease mongering‐

to create a market

•

Advancing science (EBM) vs. advancing profits (MBM)•

Selection of participants

•

Choice of comparator (no equipoise)

•

Choice of outcomes

•

Statistical vs. clinical significance

•

Duration of follow up

•

Surrogate outcomes/ composite outcomes

•

Multiple outcomes/subgroups

•

Selective reporting

•

Studies

•

Outcomes/data from outcomes

•

Interpreting results


Investigator‐

initiated trials

•

Social relevance vs. academic relevance

•

No protocol

•

Inadequate knowledge of research methods

•

No sample size calculation

•

Quality of data collection

•

Improper study designs

•

Improper analyses‐

over‐reliance on p values

•

Not publishing (after presenting in a conference/ completing a thesis)

•

Inadequate reporting of data and outcomes

•

Selective reporting of outcomes and data


THE EVIDENCE FOR THESE ASSERTIONS


Months0 12 24 36 48 60 72 84 96 108 120

Prop

ortio

n pu

blis

hed

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

month 0 12 24 36 48 60 72 84 96 108 120# published 57 354 865 248 193 74 27 20 27 2 2# remaining 3,138 2,972 2,572 1,744 1,548 1,133 1,006 734 674 100 98

Cumulative Time from Presentation to Full Publication of RCTs

Source: Scherer et al, 2005. Systematic review of 79 reports. Cochrane Library


Research funded by drug companies was less likely to be

published than research funded by other sources.

Studies sponsored by pharmaceutical companies were more

likely to have outcomes favouring the sponsor than were

studies with other sponsors (odds ratio 4.05; 95% confidence

interval 2.98 to 5.51; 18 comparisons).

BMJ, 2003


Selective outcome reportingComparison of 102 trial protocols submitted in 1994‐1995 to and

approved by the scientific‐ethics committees for Copenhagen and

Frederiksberg Denmark, with 122 subsequent publications

Chan AW et al. JAMA 2004

Findings•

Nearly two‐thirds of the studies had a change in at least one

primary outcome between the protocol and publication•

Statistically significant outcomes had a higher likelihood of

being reported compared to non‐significant findings


Suppression of unfavourable

results

Presenter

Presentation Notes

British courts uncovered evidence of deliberate, systematic suppression of unfavorable Paxil research results – no evidence of efficacy in children and increased suicide risk. In early 2004, GSK agreed to settle charges of consumer fraud for $2.5 million (a small price to pay for the $2.7 billion in yearly Paxil sales at that time)


A systematic review and meta‐analysis that avoids publication bias


The Emperor’s New Drugs: Kirsch et al 2002

•

Analysis of the efficacy data from 47 RCTs

submitted to the U.S. FDA for approval of the 6 most widely

prescribed antidepressants approved between 1987 and 1999 (fluoxetine, paroxetine, sertraline, nefazodone,

venlafaxine, citalopram)

•

Approximately 80% of the response to medication was duplicated in placebo control groups, and the mean difference between drug and placebo was

approximately 2 points on the 17‐item (50‐pt) and 21‐ item (62‐pt) HAM D Scale.

•

Improvement at the highest doses of medication was not different from improvement at the lowest doses.


PLoS

Med 2008; 5(2): e45. doi:10.1371/journal. pmed.0050045

•A previously published meta‐analysis (Kirsch et al, 2002) of the

published and unpublished trials on SSRIs

submitted to the FDA during

licensing has indicated that these drugs have only a marginal clinical

benefit.

•On average, the SSRIs

improved the Hamilton Rating Scale for

Depression score of patients by 1.8 points more than the placebo,

whereas NICE has defined a significant clinical benefit for

antidepressants as a drug–placebo difference in the improvement of

the HRSD score of 3 points.

IASCT Clinical Trial Interfaces 2011; MumbaiPLoS

Med 2008; 5(2): e45. doi:10.1371/journal.

•However, average improvement scores may obscure beneficial effects

between different groups of patient, so in the meta‐analysis in this

paper, the researchers investigated whether the baseline severity of

depression affects antidepressant efficacy.


•Data on all the clinical trials submitted to the FDA for the licensing of

fluoxetine, venlafaxine, nefazodone, and paroxetine.

• Meta‐analytic techniques to investigate whether the initial severity of

depression affected the HRSD improvement scores for the drug and

placebo groups in these trials.

•Confirmed first that the overall effect of these new generation of

antidepressants was below the recommended criteria for clinical

significance.


•Virtually no difference in the improvement scores for drug and placebo

in patients with moderate depression and only a small and clinically

insignificant difference among patients with very severe depression•The difference in improvement between the antidepressant and

placebo reached clinical significance, however, in patients with

initial

HRSD scores of more than 28—that is, in the most severely depressed

patients. •Additional analyses indicated that the apparent clinical effectiveness of

the antidepressants among these most severely depressed patients

reflected a decreased responsiveness to placebo rather than an

increased responsiveness to antidepressants.


• Conclusions: There is little reason to prescribe new‐generation antidepressant medications to any but the most severely depressed

patients unless alternative treatments have been ineffective.


OUCH! THAT HURTSWhat do we say to that?


•

Among

74

FDA‐registered

studies,

31%,

accounting

for

3449

study participants, were not published.

•

Whether

and

how

the

studies

were

published

were

associated

with the study outcome.

•

A

total

of

37

studies

viewed

by

the

FDA

as

having

positive

results

were

published;

One

study

viewed

as

positive

was

not

published.

•

Studies

viewed

by

the

FDA

as

having

negative

or

questionable

results

were,

with

3

exceptions,

either

not

published

(22

studies)

or

published

in

a

way

that,

in

the

authors

opinion,

conveyed a positive outcome (11 studies).

Presenter

Presentation Notes

Selective publication leads to clinicians believing what they read- that antidepressants are very effective when the truth is different


•

According to

the

published

literature,

it

appeared that 94% of the trials conducted were positive.

•

By

contrast,

the

FDA

analysis

showed

that

51% were positive.

•

Separate meta‐analyses of the

FDA

and

journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.

Presenter

Presentation Notes



•

The drugs were bupropion

SR, citalopram, duloxetine, escitalopram, fluoxetine, mirtazapine, nefazodone,

paroxetine, sertraline, venlafaxine

and venlafaxine

XR

Presenter

Presentation Notes



One question

•

Is a difference in 2‐3 points on the HDRS a clinically important outcome for

people with depression?


UNREAL TRIALS FOR THE REAL WORLD

Exclusion criteria in clinical trials


A Reevaluation of the Exclusion Criteria Used

in Antidepressant Efficacy Trials

Posternak

et al, Am J Psychiatry 2002; 159:191–200)


WHY THE DIFFERENCE BETWEEN WHAT WE BELIEVE AND WHAT WE

NOW READ?

What is the truth?

Is meta‐analysis rubbish or there more to it?


What is needed are higher evidence standards

While placebo controls are needed due to the high placebo

response rates in depression, comparisons with active drugs

mostly show no differences for any class of antidepressant

Use of clinically relevant outcomes ( clinical improvement,

employment, QOL, etc) rather than rating scales.

Pragmatic trials with fewer exclusion criteria

Prospective registration of trials and making data sets of results

available

large long‐term trials and

careful prospective meta‐analyses of individual‐level data

Philosophy, Ethics, and Humanities in Medicine 2008, 3:14 doi:10.1186/1747‐5341‐3‐14


Outcome measures used in psychiatric trials


Quality of Schizophrenia trials

•

Overall, the quality of reporting was poor•

Score of 3 or > was predefined as better

quality ‐

33% of North American RCTs

‐ 36% of European RCTs

‐ 43% of ROW RCTs

(46% from Canada, Middle East & Asia) Thornley

& Adams. BMJ 1998

Presenter

Presentation Notes

Overall, just under two-thirds scored 2 or less, which means that the study barely, if at all, described any attempt to reduce the potential for introduction of bias at allocation or rating of outcome.


Quality in Schizophrenia RCTs

•

Average number of sample = 65 with no change over time

•

For an outcome to show clinically significant improvement of 20% a study would need 150

participants in each arm •

Only 3% of RCTs

were of this size or greater

Thornley

& Adams. BMJ 1998

Presenter

Presentation Notes

E.G. Outcome such as clinically important improvement in mental state to show a 20% difference between groups a study would need 150 participants in each arm with alpha at 0.05 and power of 85%


Sample size in 2000 trials Thornley

1998


Rating scales in Mental Health

No other branch of the health sciences uses as many rating

scales as does mental health

Hardly any clinicians use rating scales in clinical practice to

determine outcomes

Continuous outcomes (Mean & SD) from rating scales are

assessed by significance tests and generate p values

Many researchers pay obeisance to the almighty p value

The almighty p value can be very deceptive as statistically

significant results from rating scales may prove the effects of

interventions are not due to chance but do not indicate how

effective the interventions are likely to be (statistical versus

clinical significance)


What do changes in rating scales mean clinically?

Clinicians tend to assess:severity as mild /moderate /severe andimprovement as worse, no change, mildly better,

moderately better, much better, completely well

Similar to the Clinical Global Impressions‐

Severity &Improvement (CGI)

Presenter

Presentation Notes

This study attempted to correlate the commonly used BPRS with the Clinical Global Impressions (CGI) -severity and improvement scales that rates people on severity and on improvement using a format most similar to the ways clinicians and patients/carers think. A likert type scale rating improvement as not improved through mildly and very much improved to completely well.


What do changes in rating scales mean clinically?


Why not use better anchored versions of the CGI for research?

•

There is a need for revising outcome measures used in

psychiatric research to be more clinically meaningful and

more reflective of clinical practice and use

outcomes of

importance to clinicians and patients.


Improving the standards of clinical trials

Catch them younger


www.consort‐statement.org


Ethical Considerations


CRITICAL ISSUES ON THE DESIGN AND REPORTING OF RCTS


Ingredients for a good protocol

•

Is there a justification for the trial based on the results of a

good quality systematic review?

•

Does the protocol contain a well constructed research

question with details of participants, interventions,

comparisons (including routes and doses) and outcomes,

(primary and secondary) (PICO)?

•

Does the protocol describe adequately the methods to

generate the randomization sequence, conceal allocation,

blind participants and outcome assessors and evaluate

blinding (if appropriate), and methods to deal with trial

attrition?


Target Population

Allocation

Follow up Follow up

Exposed to intervention

Not exposed to intervention

Intervention group Control group

Blinding of investigator/

subjectBlinding ofoutcome

assessment

Intention-to-treatFollow up

Allocation concealment

Method to minimize

Selection

Performance

Detection

Attrition

OutcomeOutcome

Biases


Selection bias

•

systematic differences in participant characteristics

at the

start of a trial

•

occurs at the time of allocation into comparison groups

Intervention group Control group


Selection bias

•

If groups differ at baseline in characteristics that alter

prognosis, this will influence differences in outcomes

between interventions

•

Inadequately concealed allocation in trials

overestimate treatment effects by:

•

~ 30% ( 95% CI 21% ‐

38%) (Schulz et al, 1994)

•

Most important source of bias

Schulz KF et al. JAMA 1994; 272:125‐128


Allocation concealment vs

blinding

time

randomisation

Concealment of allocation Blinding

Selection bias Performance bias & outcome detection bias

•Blinding may not be always possible but allocation concealment is always possible (even in surgical trials)•Without allocation concealment, blinding may be difficult


The effect of blinding on outcome

•

Inadequate

blinding

leads

to

performance

bias

(differential

interventions)

as

well

as

detection

bias

and

differential placebo effects

•

Inadequately

blinded

or

open

trials

tend

to

over‐estimate

results than adequately blinded trials by•

17% (Schulz et al, 1995)

•

35% (1% to 57%) (Juni

1999)

Schulz KF et al. JAMA 1995; 273: 408‐412


Attrition bias

Systematic differences in the loss of participants to follow

up

between groups (and from start of trial)

•

Participants lost to follow up, or not included in the outcome

assessment, could be different from those who remained in

the trial

Occurs over the duration of follow up

Avoiding attrition bias

Completeness of follow up

describe proportion of participants lost to follow‐up (with

reasons)


Dealing with missing data•

Analysis of ‘completers’

only

•

Intention to treat•

For continuous data

•

Imputation of simple mean

•

Imputation of regression mean

•

Last observation carried forward

•

For dichotomous data

•

Assuming worst case scenarios

•

Imputing event rates for missing values

•

Sensitivity analysis: comparing results of completers versus ITT analyses


Ingredients…continued

•

Does the protocol describe in sufficient detail the estimated sample size for the primary outcome(s) and (if needed, secondary outcomes) and its

justification? Are the outcomes clinically relevant?

•

Does the protocol describe adequately the responsibilities of investigators and methods to

ensure integrity of data collected and rules for interim analysis?

•

Does the protocol ensure that all elements that are required to be reported by the CONSORT and ICMJE guidelines will be collected and recorded?


Ingredients‐

continued

•

Are ethical issues addressed adequately in accordance with international and local

regulations and requirements?

•

Has ethics committee approval been obtained?

•

Is the trial registered prospectively in a publicly accessible Trials Register? (Avoiding reporting

biases)


Ingredients‐

when reporting results

•

Is the trial registration number reported?

•

Have deviations from the protocol been reported?

•

Is there a description or diagram of participant flow though

the various stages of the trial?

•

Have absolute values been reported in addition to

proportions for binary outcomes?

•

Have means as well as standard deviations (or standard

errors) and numbers of participants for each intervention

been reported for continuous outcomes?

•

Have effect measures and confidence intervals been

reported in addition to (or instead of) p values?


Ingredients‐

when reporting results

•

Have drop‐outs and withdrawals been described? Was an

intention to treat analysis used?

•

Have post‐hoc analyses and sub‐group analyses been kept to

a minimum?

•

Have all important outcomes been reported?

•

Have funding sources and conflicts of interest been

declared?


HOW NOT TO DO IT

Assessing the validity of interventional research in India


The internal validity of RCTs from India“Sub-optimal …or shall I shall say..Poor show, old chap?”


2004 & 2005 compared to 2007 & 2008

•

Of the 65 journals:•

38

(59%)

in

2005

and

37

(57%)

in

2008

mentioned

the

ICMJE

requirements in their instructions for authors,

•

Only

20

(31%)

in

2005

and

22

(33%)

in

2008

specifically

required

authors

to

submit

manuscripts

in

accordance

with

the

CONSORT

statement.

•

Of

151

RCTs

published

in

2004‐2005,

and

145

RCTs

published

in 2007‐2008:•

Only 4/13 (31%) of selected CONSORT items were reported in > 50%

of

trial reports.

George A, Kirubakaran

P, Barnabas J, Tharyan

P. 3rd

South Asian Regional

symposium in Evidence‐informed Healthcare Jan 2010


Unhappy Endings

Improved

Improved

Improved

No change

No changeNo change

No change

No change

No change

No change

Worse

Worse

Worse


Ethical Considerations

108 (71)107 (73)

103 (68)118 (81)

39 (25)66 (45) *

11 (7)60 (41) *

0 20 40 60 80 100 120

Number of Trials (%)

Ethical Committee ClearenceInformed Consent

Source of FundingConflicts of Interest

Figure - II: Reporting of ICMJE Requirments

2007-2008(145)2004-2005(151)

*Conflicts of Interest

: Odds Ratio

2.4;

95% CI (1.4 ‐

4.0)

*Source of Funding

: Odds Ratio

8.9; 95% CI (4.2 ‐

19.2)


More unhappy endings: The internal validity of RCTs

in Mental Health in LMICs

Internal validity measure N=177

Sequence generation 30 (17%)

Allocation concealment

Blinding

21 (12%)

109 (62%)

Assessment of blinding 0 (0%)


Poor quality of research

•

Fourth Congress on Peer Review in Biomedical Publication concluded that:

•

Medical journals are full of serious methodological errors

•

Journal editors are giving no time, energy and thought to their craft

•

Studies are published that reach false conclusions

BMJ, 2001


Whose fault is this?

•

Editors

•

Peer reviewers

•

Researchers

•

Institutions

•

Institutional review boards•

Ethics committees

•

Research committees

•

Funders of research

•

Educational programmes

and educators

•

Implementers of research evidence

•

Consumers

•

The system of complacency

Chaltha

he!

Its only a PG thesisanyway


IF YOU WANT A GREAT ENDING..

YOU NEED A GREAT BEGINNING…

AND MIDDLE…

Improve the design

and conduct of research..

To improve the reporting of results

of research

Ensure that trials are prospectively registered with IRB approval to prevent reporting biases


Clinical Trials Registry‐

India

www.ctri.in

The CTRI is a Primary Register of the WHO-ICTRP


Mission and Vision

Mission•

Encourage

all

clinical

trials

to

be

prospectively

registered before enrolment of first patient•

To comply with ICMJE and WHO‐ICTRP requirements

Vision•

Ensure registration of all clinical trials prospectively

•

Ensure

voluntary

disclosure

of

all

items

in

the register :

•

To improve transparency

•

To improve internal validity of trials

•

Conform to accepted ethical standards


Registration Data Set: CTRI specific items

Trial registration data set with explanations can be downloaded


Compliance

100% : 13/20

95‐99%: 5/20

90‐95%: 1/20

85‐90%: 1/20


Ethics committee

approval:100%

Random sequence

generation: 82.6%

Allocation

concealment: 76%

Blinding 85%


Comparing the endings and beginnings

Journals

2004‐2005(N=151 )

Journals

2007‐2008(N=145 )

CTRI2009 Jan

(N=144)

CTRI2010Aug

(N=1002)

Verdict

Random

Sequence

Generation

38% 55% 83% 78%CTRI

better

Concealment of

allocation 16% 21% 76% 84%

CTRI

better

Blinding 64% 46% 85% 88%CTRI

better


Central Drugs Standard Control

Organization

Directorate General of Health Services, Ministry of Health and Family Welfare, Government

of India

http://cdsco.nic.in/

http://cdsco.nic.in/


E‐mail from Dr. Surinder

Singh;

Drug Controller of India

•

“The registration of clinical trials is mandatory in most of the

developed countries and in India it was made Advisory in the

Clinical Trial Permissions issued by office of DCG(I),

•

However the clinical trial registry was made mandatory from

15th

June, 2009 for all the applicants to whom the permission

is granted by office of DCG(I).

•

It may be mentioned here that while the number of trials

registered till Dec, 2008 was 137, the number of trials

registered between Jan, 2009 to Nov, 2009 are 464, out of

which around 373 trials are registered after 15th

June, 2009

after it was made mandatory by the Office of DCG(I).”


WHAT’S NEXTWhat about investigator initiated trials?


WORKING WITH MEDICAL JOURNAL EDITORS IN INDIA IN

ENDORSING TRIALS REGISTRATION

Meeting with Medical Journal Editors (ICMR)

October 9 2007


Editorial policy on trials registration


Get the Evidence Right

The Devil is in the Detail

Don’t

Just Do It; Do It Right


“When you know something, to hold that you know it, and when

you do not know something, to allow that you do not know it;

that is knowledge.”

Confucius (551 BC ‐

479 BC)


Join us: www.cochrane‐sacn.org

study design: the blueprint for success tharyan.pdf · prathap tharyan md, mrcpsych. professor of...

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