Tuesday, October 07, 2008

Power of words and Safe Communication

Words that end up in court
Altered records, defect, falsification, hazardous, illegal, incompetence, inferior, negligent, reckless, wrongdoing

Fighting words
Allege, argument, complaint, careless, dispute, idiot, inefficient, liable, misinform, problem, shoddy, shortsighted

Loaded questions and negative words
"I am not a cook"
"I am not a bimbo"
How would you respond?
Did the clinical trials go badly?
Do you always drive like a maniac?

Phrases to make people defensive
Apparently you are not aware...
Contrary to your inference...
I don't agree with you...
Let me make this perfectly clear...
You obviously overlooked...
And just for your information...

Phrases that will get you more attention than you want
delete this email
do not distribute
shred this memo
do not tell (insert name here)
can we get away with it?
They'll never find out
I have serious concerns
I don't care what you do
This might not be legal
let's meet to talk about the thing I mentioned last night

Avoiding commenting on potential
Potential liability issues:
Risky way: if we do not conduct the tests I propose, the company could face serious FDA regulatory problems and product liability suits
Safer way: I believe this protocol employs sound research methodologies that will yield scientifically valid data and should be favorably reviewed by the FDA

Be specific and detailed about information sources:
Risky way:Managers send and receive an average of 178 messages a day
Safer way: A recent Gallup poll showed that managers send and receive an average of 178 messages per day

Risky way:Previous studies show the drug is safe
Safer way: According to the 2005 viral transmission study done by Dr. Jackson...

Risky way: He says he won't use our product because the rate of viral transmission of hepatitis C is too high
Safer way: Dr. Bowers had concerns about the possibility of viral transmission of hepatitis C. I explained to him about our...

Close 'open loops'
An open loop
  • The investigator again questioned the safety of the new protocol
Closing the loop
  • In response to the investigator's query about the safety of the protocol...

Know when not to respond
  • when you don't know
  • when it falls outside your expertise area
  • potential hot button issues
  • challenging editors and auditors

Monday, October 06, 2008

Source data in EDC trial

One of my friends asked me what would be the source data and how to verify if the data was directly entered into EDC. A recent article in clinicaltrialsonline.com answered this question. it looks like this is the topic covered under FDA's new guidance "Computerized Systems Used in Clinical Invesitgations" http://www.fda.gov/cder/guidance/7359fnl.htm.

Scenario 1: Data are first captured on paper and then manually entered into a computerized system. Source data are the paper documents. Examples: Data collected at clinical sites, IRBs, and medical practices.

Scenario 2: Data are first captured electronically into a computerized system and then manually entered into another database. Source data are the electronic records in the computerized system. Examples: Data collected at clinical sites, diagnosis after test evaluation in medical institutions.

Scenario: 3: Data are first captured electronically into a computerized system. Source data are the electronic records in the computerized system. Examples: Data collected at clinical sites, clinical laboratories, analytical laboratories, etc.

To read the full article, please visit "http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/article/articleDetail.jsp?id=546112&sk=&date=&pageID=3"

New Data Management acronyms

The recent effort to standardize the clinical data acquisition results in a lot of new acronyms. Some of them are listed below. A lot of these terms are in CDISC standards http://www.cdisc.org/standards/index.html

CDASH - Clinical Data Acquisition Standards Harmonization – Data acquisition (CRF) standards
CDISC - Clinical Data Interchange Standards Consortium http://www.cdisc.org
ODM - Operational Data Modeling – CDISC trasnpport standard for acquisition, exchange, submission (define.xml) - http://www.cdisc.org/models/odm/v1.1/odm1-1-0.html
SDTM - Study Data Tabulation Model - http://www.cdisc.org/models/sds/v3.1/index.html
SDS - Submission Data Standards - http://www.cdisc.org/models/sds/v2.0/
SEND - Standard for Exchange of Nonclinical Data
ADaM - Analysis Dataset Model
EDC- Electronic Data Capture
RDC - Remote Data Capture
CTD - Common Technical Document
eCTD - electronic Common Technical Document

Adobe Acrobat Resource Center - weblinks

Training & Resources:
Acrobat for life sciences blog - http://blogs.adobe.com/acrobatforlifesciences/
Acrobat legal links online - https://www.regonline.com/builder/site/default.aspx?eventid=136003
Adobe solutions for life sciences website - http://www.adobe.com/lifesciences/
Adobe and the SAFE-Biopharma Association - http://www.adobe.com/lifesciences/safe.html
SAFE white paper - http://www.adobe.com/lifesciences/pdfs/safe_wp.pdf
Adobe solutions for electronic submissions solution brief - http://www.adobe.com/lifesciences/pdfs/electronic_submissions_sb.pdf

Support & Development
Adobe PDF for Developers Blog - http://blogs.adobe.com/pdfdevjunkie/
Acrobat 8 deployment techniques eSeminar - https://admin.adobe.acrobat.com/_a227210/p92416557
Adobe Support Knowledgebase, Join the acrobat forum and the acrobat user group - http://adobe.com/support
Free acrobat tutorials, user groups, and blogs - http://www.adobe.com/cfusion/designcenter/search.cfm?product=acrobat&term=acrobat&topic

Free Download & Trials
Adobe 8.0 Professional Free Trial Download- http://www.adobe.com/products/acrobatpro/tryout.html
Adobe document center free trial - http://www.adobe.com/products/onlineservices/documentcenter/features.html
ISItoolbox pharma edition free trial - http://www.isitoolbox.com/ProductInformatoin/PharmaEdition/tabid/724/Default.aspx

Sunday, October 05, 2008

Introduction to pharmacokinetics and pharmacodynamics

The book by Drs Tozer and Rowland is pretty good.
About dose "To paraphrase Paracelsus, who lived some 500 years ago, "all drugs are poisons, it is just a matter of dose." A dose of 25 mg of aspirin does little to alleviate a headache; a dose closer to 300-600 mg is needed, with little ill effect. However, 10 g taken all at once can be fatal, especially in youn children.

About the definition of PK and PD: In simple terms pharmacokinetics may be viewed as what the body does to the drug, and pharmacodynamics as what the drug does to the body.

On genetic variability in drug response: If we were all alike, there would be only one dose strength and regimen of a drug meeded fro the entire patient population. But we are not alike; we often exhibit great interindividual variability in repsonse to drugs. In rare caes, the "one-dose-for-all" idea, suffices.

About Plasma: In practice, plasma is preferred over whole blood primarily because blood causes interference in many assay techniques. Plasma and serum yield essentially equivalent drug concentrations, but plasma is considered easier to prepare because blood must be allowed to clot to obtain serum. During this process, hemolysis can occur, producing a concentration that is neither that of plasma nor blood, or causing an inference in teh assay.

About the differences among Plasma, Serum, and Whold Blood:
Plasma: Whole blood is centrifuged after adding an anticoagulant, such as heparin or citric acid. Cells are precipitated. The supernate, plasma, contains plasma proteins that often bind drugs. The plasma drug concentration includes drug-bound and unbound to plasma proteins.
Serum: Whole blood is centrifuged after the blood has been clotted. Cells and material forming the clot, including fibrinogen and its clotted form, fibrin, are removed. Binding of drugs to fibrinogen and fibrin is insignificant. Although the protein composition of serum is slightly different from that of plasma, the drug concentrations in serum and plasma are virtually identical.
Whole blood: whoe blood contains red blood cells, white blood cells, platelets and various plasma proteins. An anticoagulant is commonly added and drug is extracted into an organic phase often after denaturing the plasma proteins. The blood drug concentration represents an average over the total sample. Concentrations in the various cell fractions and in plasma may be very different.

On site of administration:
Intravascular: refers to the placement of a drug directly into the blood - either intravenously or intra-arterially.
Extravascular: include the intradermal, intramuscular, oral, pulmonary (inhalation), subcutaneous (into fat under skin), rectal, and sublingual (under the tongue) routes.
Parenteral administration: refers to administration aprat from the intestines. Parenteral administration includes intramuscular, intravascular, and subcutaneous routs. Today, the term is generally restricted to those routes of administration in which drug is injected through a needle. Thus, although the use of skin patches or nasal sprays (for systemic delivery) are strictly forms of parenteral administration, this term is not used for them.