The SPS will be in its tenth year of existence in 2009 and safety pharmacology as a defined scientific enterprise is also about a decade old. Have we made an impact on the safety of drug development? How is safety pharmacology data viewed by our management in the pharmaceutical industry; are we giving good value for their investments? How are our data being received by regulators? Do we contribute effectively to the safety of early clinical trials? Is our data being taken seriously and is it thought to be predictive by the authorities?

The program committee for the 2009 annual meeting to be held in September in Strasbourg, France is contemplating organizing some programming that will examine this type of question. It should however not only give Safety Pharmacology a ten year “report card” but also look into the future for areas of improvement or expansion.

We’d love to get your input and ideas to give some content to these important questions to help guide us in identifying critical themes and finding appropriate speakers to address them. We may attempt either a panel discussion format or perhaps a debate setting, but regardless of how it turns out, we would appreciate your contribution!

Dear members

Are any of you aware of a realiable supplier of a testing kit for the kidney injury molecule-1 (KIM-1)

Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a specific and sensitive biomarker of kidney
injury. Scand J Clin Lab Invest Suppl. 2008;241:78-83.

Regards
Tomas Mow, Head of Safety Pharmacology, H. Lundbeck.

USDA Policy #3 (Nov 7, 2007) requires the use of pharmaceutical compounds in animals, specifically covered species.  Interested in how other pharmaceutical companies and CROs are handling this new guideline with respect to any and all compounds other than NCEs or NBEs that are administered.  Materials used for analgesia, anesthesia, euthanasia and any animal health medications would most certainly be pharmaceutical grade, but what about reference compounds, competitor compounds and various pharmacological tool compounds used in the performance of many assays?

Consortia collaborations offer a fast and efficient way to develop methods and scientific understanding in principal areas of research. This survey, conducted with the support of the Safety Pharmacology Society, had several objectives: to identify ongoing consortia projects probing areas in the field of safety pharmacology, and to make available to the SPS’s members, information about these programs.

Lessons learned, in terms of managing and contributing in such projects will be presented. The potential role of the SPS as a facilitator of such projects will also be explored.

This will hopefully kick off a discussion about the value of collaborative programs and their potential benefits to the participants.

A survey was e-mailed to members of the SPS. Responseswere collected online. 14 projects involving more than 30 companies were identified. The projects covered the areas of drug-induced pro-arrhythmia (4), drug-induced cardiotoxicity (2), drug dependence and abuse liability (2), cardiovascular genomics (1), study of human ion channels (1), comparative biology and scaling of results across different species (1), and zebra fish as a pre-clinical model (1).

The SPS is in a unique position to take the lead by collecting and disseminating information about consortia projects (both completed and in-progress) and identifying new areas where further research is needed. Creation of Special Working Groups around specific topics under the auspices of the SPS could serve to facilitate consortia projects to the benefit of patients, safety pharmacologists, the society, and regulatory bodies alike.

Prior to candidate recommendation from discovery, most groups conduct some sort of “ancillary” cardiovascular study. The question is in what model?

Could folks share the in vivo model or models that are typically used (eg. dog, monkey, rat, conscious/anesthetized, etc) to support the advancement of a compound into the toxicology phase of development.  Also, if any models used are established in the company, or outsourced.

Folks - this really has a great feel and many thanks to all those taking it to this high level so quickly.

I earnestly hope that this adds novel extra value for the membership.

Hopefully this serves to drive up our membership and interest in the website in parallel .

Perhaps we should consider a ‘live’ demo in Madison during the annual meeting so those new delegates really see this new approach.

Perhaps we  should also reflect on how we communicate with those visitors to Madison who,  like myself, who are not native English speakers …..

Ian M.

The electrocardiogram is taken routinely in conjunction with toxicological studies in larger animal species including the dog, primate or pig. They have been used in the past to document heart rate as well as to identify gross electrocardiographic changes that might occur over time due to such things as myocardial ischemia or myocardial hypertrophy.

Due to the recent attention to the detection of drug-induced effects on ventricular repolarization, there is an increased interest in analyzing ECGs more thoroughly to include the standard intervals and wave form durations. Of particular note is the meausrement of the QT interval for detecting hERG-induced delays in ventricular repolarization. The ICHS7a guideline suggests that in vivo evaluation of the potential for drugs to prolong the QT interval might be addressed in toxicological studies.

Over the past years there has been an increased awareness of the challenges involved in doing a high quality preclinical, in vivo evaluation of potential effects on ventricular repolarization. The important role of heart rate-induced effects on repolarization must be taken into account. We know now that various physiolgoical factors can affect the QT interval. Furthermore, the sensitivity of a given test system to pick up a given change in the QT interval is dependent upon the variability of the measured parameter. Above all, a robust evaluation of the potential effects of a drug on ventricular repolarization requires a high quality ECG, at best recorded frequently enough to allow for a thorough analysis of time-dependent effects.

The question posed here is whether or not the quality of ECGs, as have been taken routinely in the past (and still presently) are adequate for a reliable assessment of drug-induced prolongation of the QT interval?

Have you evaluated ECGs from toxicological studies and been satisfied with their quality?

Is the amount of data collected in “traditional” tox studies sufficent to base such an assessment?

Are the animals used in a tox study in an acceptable physiological state to consider them for use in a “non-clinical QT study?”

Do you know of anyone who has done a power analysis on ECG data coming from a tox study? What size of effect on QT can one reasonably detect with the number of animals typicllyused for tox studies?

What is feasible to improve quality of ECGs in tox studies and what are the associated costs and efforts needed to affect an increased quality? Would most sponsors be willing to invest to improve this readout?

We would appreciate hearing about your experiences and opinions on this matter!

Dear Collegues,

We are very excited to have reached launch stage with our blog activities.  We hope you share this excitement with us.  As true Safety Pharmacologists we want to strive for excellence in this endeavour and welcome your comments.  Let us know what you like, even what you LOVE!  Let us also know what needs improvement, in process, appeal, user friendliness and helpful user FAQs for us to post.

We have deliberately set this up as a very interactive blog that enables the posting of actual articles and opinion beyond the comment section. 

The comment section is intended to be very simple to use - we hope you find that to be the case.  Please, if there is anything at all that you believe would make this even simpler still this is the place to let us know.

The posting section will take a little more investment in your time but there is a great instruction section to help you with this - we want to hear from you if there is anything that we have missed.  This can take on the feel and flavor of a bona fide blog with the addition of media to spice up its visual appeal.  We encourage you to give rein to your creative side and use the capabilities to the fullest.

Looking forward to hearing back from you regarding this latest adventure into cyberspace!

When going to save after that there is no option to continue from that screen to publish

When publishing I came back to this screen - where is my post :)  It would be good to redirect to the posting page.  Where is the post?

Thought I would put some of my comments in here and give the blog a test run. 

I tried to make this entry first in the response entry and it was only after I had typed it all in and pressed the submit button that I then discovered that you have to be logged in to add a comment.  We should let people know this up front.  I could see someone getting frustrated with this and not bothering to continue - and we want to do everything we can to encourage people to participate.  Fortunately, I had copied my comments - so here they are again (see below). 

I have some edits to opening paragraph betweent the hyphens. 

Do you have questions or comments about various topics in Safety Pharmacology, but -do- not know how to get feedback?  -Do you have ideas and opinions to share- with other safety pharmacologists?  What can you do to get a timely answer or -feedback-?

Is it possible to add in some simple editing tools for this section?

Can we have a review entry option prior to posting the comment as it will appear on the page?

This was all good as it gives me more comments to make about user friendliness

Also, on the page that I was sent to that said you have to log on first this would be a good place to provide that option. 

When I used the back button I did not see anywhere on the initial page to log on either - I think it would be good have some very explicit instructions closely linked with any points that data can be entered

I am wondering whether we should think through the use of tags - does the system recognise upper and lower case as a single entry.  Are we going to review for consistency.  I entered a tag for this post with upper and lower case and they do appear to be recognised independently.  It would be good to show preferred options as a drop down from the tags if possible and ;advise on preferred format.

Re the options at the bottom of the screen can we have a quick summary of this at the beginning of the entry - people will generally not see these options until the very end if at all.

A discussion of when and if people will use the password protect would be useful and the pros and cons.

What if I want to change my authorship - that option is not available - I see that it is based on my log on id which might not necessarily be my name.

If I preview this post then there is nowhere to then submit.  I had to come back to the edit page.

Colleagues,

To follow on the SP.EAK welcome…yes, we have a blog!  We are interested in your thoughts not only on the science we may exchange but also on your creative juices - we Safety Pharmacologists are a talented bunch.  Share your ideas for this blog -

What additional areas would you like to see covered in addition to the raw science? 

Do you have design ideas for this site?

Don’t be shy we want to hear from you - so blog away…