It's not all work, work, work...

If you want to join in the fun...

CRfocus 20(12) - December 2009

“It’s Christmas!”

• Jingle bells, jingle bells, jingle all the way… someone had an adverse event and phoned the MHRA
• God rest ye, merry gentlemen, let nothing thee dismay… especially not these patient recruitment figures…
• The holly and the ivy, when they are both full grown… should be taken off that long-term paediatric study
• Last Christmas I gave you my heart, but the very next day you gave it away… so we need to put more resource into developing immunosuppressives
• Rudolph the red-nosed reindeer… should probably report that as an adverse event
• You better watch out, you better not cry. Better not pout, I’m telling you why: Santa’s decision on exclusion criteria is final!

Another Ten Things...

1. A stack of ‘stickies’ pre-printed with the signatures of famous Key Opinion Leaders
2. A copy of “ICH GCP for Dummies”… and a blank Training Request Form
3. A notepad made from recycled SUSAR reports
4. A bumper package of data queries, to be resolved by December 31st
5. “Clinical Trial: The Board Game” to while away those long evenings while visiting the in-laws
6. A box of tablets not destroyed after last year’s terminated study, containing placebo… you think…
7. A year’s membership of FacelessBook, the social networking website exclusively for preclinical professionals
8. Notification of an MHRA inspection on January 4th
9. A P45
10. Nothing!

CRfocus 20(11) - November 2009

Ratings war

• “Britain’s Next Top Statistical Model”, in which Lisa Snowden discusses appropriate powering, standard deviations and Bayesian analysis with members of PSI.
• “Overheads Over Heels”, in which R&D departments compete too see who can go through the best song and dance routine talking to pharmacy, imaging etc. before agreeing the contract and fee structure for a study to take place in their Trust.
• “Masterfile Goes Large”, in which amateur CTAs are tested on their knowledge of essential documents and prepare a three-course audit-readiness plan for a project manager who “likes his pud”.
• “Auditors in the Jungle”, in which twelve auditors are taken to a jungle of the South-East Asia for forced to tackle tasks of endurance. Each week, viewers phone in to vote on whether any of them are allowed to come back home.
• “First-in-Man Big Brother”, which is exactly like Big Brother, but with additional injections. The role of Davina McCall is played by Professor Sir Gordon Duff.

Why don’t we call it…

• Susartapine
• Nevawerx
• The Ultimate Remedy
• Plassibo
• Infarctomatic
• FxLess
• Quax

Another Ten Things...

1. Minutes taken to complete a CRF
2. Support staff required to rectify luminary failure
3. Contract personnel per IMP dosed
4. Site fee per hour of negotiation
5. CRF pages completed per adverse event
6. Staff turnover per project milestone
7. Variance in number of Investigator Brochure pages read
8. Projected peak sales per adverse event
9. Elapsed days to evaluate performance metrics system
10. Nothing!

CRfocus 20(10) - October 2009

If it’s good enough for Dan Brown…

• Franz Kafka wrote about blattaria gene knock-out therapy, and “The Trial” is already a classic allegory for the perils of poorly-conducted informed consent.
• The French folk tale about “stone soup” is clearly an allegory for homeopathy.
• One of Jane Austen’s early drafts read “It is a truth universally acknowledged, that a single man in possession of a good fortune, must be in want of a selection of healing crystals.”
• … and don’t get us started on the assorted potions and spells in Harry Potter…

Elevator pitch

• Dorothy moves to Australia to work as a Research Nurse. She gets lost on her first day at the hospital, and follows the yellow lines from ward to ward to the Green Zone, trying to meet up with her investigator. On her way, she joins forces with a sub-investigator, a fellow research nurse and an R&D office administrator, and is followed by an investigator working in another therapeutic area, who really likes her red shoes…
• A young CRA called Marty finds that the investigator at one of his study sites has developed a time machine built into a DeLorean car. He travels back in time and inadvertently prevents the study from ever taking place, causing a paradox. It takes a performance at the office Christmas party and a lightning strike to resolve the paradox. Ironically, the study was into early-onset Parkinson’s disease.
• Young socialite Rose DeWitt joins an ‘unsinkable’ CRO as a data manager. She meets sales rep Jack Dawson, who whisks her off to a sales conference party and wins her heart. She decides to run away from her career in data management as Jack says sales makes him feel he’s “the king of the world”… but sadly the CRO hits a commercial iceberg and they’re both made redundant.
• Benjamin is brought in to manage a project that is already close to database lock. Strangely, data starts disappearing and patients keep leaving the study, leading him to wonder whether the entire project is running backwards…
• [That’s enough blockbuster rewrites, Ed.]

Another Ten Things...

1. No more investigator meetings in Cleethorpes
2. Hot-desking and flexible working become fashionable again
3. CRAs starting to report cold-calling from recruitment agencies again
4. Managers can visit India or China without their staff having panic attacks
5. Mergers are claimed to create value, not simply to enable lay-offs
6. Decline in pharma activity on Twitter as marketing folk have some real work to do!
7. Everyone expects to leave the whole-company meeting with their job intact
8. The “recruitment crisis” headlines return
9. Monitors stop doing 100% SDV “to pass the time”
10. Nothing (isn’t that a bit cynical, Ed.)

CRfocus 20(09) - September 2009

Those Lousy Acronyms (TLAs)!

If there’s one thing we have too much of in this industry, it’s acronyms. While it’s undeniably useful to be able to say “ask the CTA to pull out the TMF”, “have the CRA email the PI about the REC’s PIL query” or “tell the PM it’s impossible for me to SDV all these CRFs today”, they can make our world seem rather impenetrable for newcomers and make the rest of us feel like we’re speaking in code! So, let’s suggest a few alternate definitions for key acronyms… if you can come up with any more, please do send them in:

• SAE = Someone Almost Endangered
• IVRS = Irritatingly, Vowels Ruin Software
• GMP = Generally Made Perfectly
• TMF = Three Messy Folders
• IMP = Interesting Mauve Pill
• QALY = Quite A Long Year
• ISRCTN = It Seems Rather Clever, Take Note

Another Ten Things...

Readers will have noticed the increase in the speed and variety of news stories being reported over the past few months, via the ICR website (www.icr-global.org/resources/news/), our RSS feed and Twitter page (http://twitter.com/CRfocus). However, here are “Ten news stories that weren’t covered by the world’s clinical research media…”:

1. Company says new acquisition is a poor strategic fit, expects integration problems

2. Investigator tells placebo cohort “don’t bother coming back”

3. Report warns of doctor surplus by 2025

4. Sales Director moving to competitor: “I was about to get fired anyway”

5. Late phase study completes recruitment on time, within budget

6. Old investigator brochures found at car boot sale

7. Journal article on homeopathic medicine “contains highly-diluted scientific fact”

8. Sponsor to “press on regardless” after Phase II study shows no treatment effect

9. Patient signs informed consent form “Mickey Mouse” as a joke, given mint as joke IMP

10. Study inconclusive because nothing was done

Summer job?

Some clinical research professionals are taking a well-earned rest over the summer, while waiting for the turbulence of studies on hold and job markets in flux to sort themselves out. Still, you can take the professional out of clinical research, but you can’t take clinical research out of the professional… here are some alternative projects people have been pursuing over the summer:

• Taking informed consent from neighbours for a second helping of tea and cake at the village fête.
• Drawing up a GANTT chart to identify the critical path to deliver cousin Jenny’s wedding on time, within budget and fit for purpose.
• Statistical analysis to determine which sunscreen minimises the presence of reactive oxygen species.
• Routine audit of family tent, sleeping bags etc. for compliance with GCP (Good Camping Practice).
• A three-armed paediatric cross-over study in 5-, 7- and 10-year olds to test the comparative effectiveness of EuroDisney, Granny’s house in Scotland and a “stay-cation” outside Basingstoke as placebo.

CRfocus 20(07) - July 2009

We’re all going on a… summer holiday

• Visitors to Lindau on Lake Konstanz might like to visit the Bistro Placebo. Perhaps you’ll get the food you order, perhaps just something that looks similar…
• If you are feeling particularly adventurous, you might want to go trekking in the Susar Mountains, in central Pakistan
• People who routinely take their work home with them will love a camping holiday in Silver Springs, Maryland, or possibly a cruise from Canary Wharf Pier to Limehouse Basin.

Less troubling side effects

• Intermittent blinking
• Astral travelling
• Over-appreciation of music
• Involuntary inhalation/exhalation
• Raised levels of conscientiousness
• Uncontrollable desire to walk on the cracks in the pavement

Another Ten Things...

1. Return unusued study drug to manufacturing to be chemically modified into next drug candidate
2. Re-use informed consent documents from last year’s study
3. Print only one Investigator Brochure for the entire study; ask sites to circulate
4. Conduct all patient consultations by teleconference
5. Pool blood samples from all patients before analysis (we’re only going to average the results anyway…)
6. Reduce refrigerant usage by studying heat-sensitive compounds only in Greenland
7. Walk to monitoring visits
8. Transport blood samples by carrier pigeon rather than van/plane
9. Redesign all manufacturing syntheses to begin with bovine methane and carbon dioxide
10. Nothing!

CRfocus 20(05) - May 2009

Essential reading

• File Notes from Underground, Fyodor Dostoyevsky’s masterpiece of study administration.
• Treasure Island by Robert Louis Stephenson, where a crucial early role is played by Double-Blind Pew.
• From Russia with Blood by Ian Fleming, where James Bond is instructed to retrieve patient samples from a study site in Moscow.
• The Dice Man, a story of randomisation by Luke Rheinhardt.
• The Bible, specifically the first part of Genesis, which should inspire project managers everywhere.
• and, of course… The Trial, in which Franz Kafka’s protagonist is turned into a giant cockroach in an unsuccessful early phase study.

Another Ten Things...

1. Enabling all patients involved with a drug’s in clinical development to vote on whether it receives a Marketing Authorisation.
2. Allowing patients to choose their own dosing regimen, to better model real-world compliance.
3. Conducting research phases in reverse order, bringing the pivotal Phase III study to the beginning of the process.
4. Requiring all physicians to take part in a Phase I study as part of their medical training.
5. Charging patients to participate in a study, to enable market testing of different price-points.
6. Flying patients to a central location after referral, so a global study can be run at a single site.
7. Conducting clinical development entirely in China, followed by small, local ‘bridging studies’ in all other regions.
8. Commissioning a CRO to run a multi-arm pivotal study for multiple sponsors, to assess comparative efficacy before registration.
9. Producing a reality TV programme in a clinical trials unit, for ultimate transparency plus revenue from votes for which investigator to ‘evict’.
10. Changing nothing!

CRfocus 20(04) - April 2009

Bag it up…

• Status bar. Like the “available”/“do not disturb” status on office phone systems, Skype etc., this would enable delegates wandering round the exhibition hall to avoid unwanted attentions from over-zealous exhibitors… or to attract them, if the delegate is actively looking to find a new supplier, change jobs etc.
• Pedometer/battery charger. What we do more of at conferences than anything else is walk. It seems such a waste not to know the good all this walking is doing for our bodies. More ecologically-conscious delegates could also use the motion from walking, bag-swinging etc. to recharge mobile phones and laptops without increasing their carbon footprints.
• Tardis-like dimensions. Exhibitions are a great place to pick up goodies, from pens and sticky-notes on up. Even if you don’t win that luxury hamper or Nintendo Wii, you’ll need far more space to carry your assorted goodies than any bag confined to normal spatial dimensions could accommodate. It could also hold a few spare pairs of shoes to help cope with all the walking!
• Easily personalised. Personalisation is all the rage these days: outfits, mobile phones, laptops etc. all enable us to express our personalities, so why not our delegate bags. Bags could be distributed with assorted coloured strips and stickers to affix to our bags as we choose, to help us stand out, as conversation starters (good for all you networking mavens) or simply to make sure you don’t lose yours in the lunchtime scrum or at the conference cloakroom.
• Biodegradable. Particularly important for a bag with none of the above features, even the most dull and basic bag would be improved if it could be composted at the end of the conference!

Clinical research goes rap?

• Just go and jam it, cause I’ll help you understand it: the rhythm and style of this clinical trial, and while other bad rappers are hangin’ content, I’m here to represent for this eluting stent: went through other phases, efficacious like crazy, preliminary findings set to amaze, see. But that’s no guarantee, there’s always a risk, and you’ve always got the right to step back and say nix. So you can be assured we’d like you in the core plan, but I’m here to ensure your consent is informed, man!
• Randomisation, what’s the score? Well, I’m here to let you know what blinding’s for: you got active and placebo in the two study arms. Active should be good, but it might do you harm. Placebo does nothing, you might expect, but just watch out for that placebo effect! We’ll give you something: we won’t know what, and then analyse before we check what you got. Just in case you’re wonderin’: why we do this in trials is, it’s important so we don’t introduce a bias. So we don’t know what you took until the final extent… well, unless we unblind for an adverse event! Word!

Another Ten Things... we hope sales & marketing won’t say to clinical

1. … but the candy coating would help it melt in the mouth, not in your hand…
2. We’re using viral marketing to promote an anti-viral drug… oh, the irony!
3. We can meet the £30k/QALY threshold, but only if you can prove 90% of the entire population will benefit.
4. Does it work in people with green eyes? The model we’ve got for the ad campaign has green eyes…
5. We’ve been beaten to market; can you go back and do that phase 3 work again with the other treatment as a comparator?
6. Can you make the tablet bigger for the US market, so it looks more important?
7. Kate Moss mentioned research using ‘virtual people’; did she mean Second Life… or lab technicians?
8. We’ve spent your development budget… but the launch party will be terrific!
9. We love the efficacy profile, but can you make the pill orange?
10. Nothing!

CRfocus 20(03) - March 2008

Getting the joke vs research integrity

As discussed in the March 2009 editorial column, there is a danger of some people taking spoofs and hoaxes too seriously. In response, we’ve tried to come up with a few more accurate attempts at humour:

• I wouldn’t say my project manager’s mean… she’s firm but fair about trial expenses, which is particularly important in these difficult economic conditions.

• Did you hear the one about the disorganised CTA? No, nor did we…

• What’s the difference between a sales rep and a snake? One’s scaly, slithers along the floor and can’t be trusted… and the other’s a sales rep!

• A CRA, a project manager and a principal investigator go into a bar… isn’t that in breach of the ABPI code of conduct?

• [Stop it, they may be accurate but they’re not funny! Ed.]

‘Abba’ great time at the ICR conference

We’re very excited about the ICR Annual Conference in Birmingham later this month, not least because of the Abba tribute band and 70s theme for this year’s Gala Dinner. As a result, we thought we’d ‘adapt’ some Abba classics to better fit the world of clinical research:

• I Have a Dream (the project manager’s wish…)

• Take a Chance on Me (… but do a feasibility study first!)

• Gimme! Gimme! Gimme! (A Patient, Anytime)

• I Do, I Do, I Do, I Do, I Do (the ‘informed consent’ song)

• Does the MHRA Know?

• The Winner Takes it All (… until the patent expires and generics firms get in)

• Super Trouper (anthem for CRAs and CTAs everywhere)

Another Ten Things... you wouldn’t say during an informed consent conversation

1. “Now, this is the bit that all the other patients objected to…”

2. “You’re free to leave the study at any time… if you don’t mind being called a quitter.”

3. “Yes, if you really want to you can put your patient diary on Facebook.”

4. “We’ll publish the results… or they’ll come out in the courts, whichever’s sooner.”

5. “It’s an experimental treatment: we don’t know how much better it is than the alternatives.”

6. “Don’t worry about reading that, I’ll sign it for you later.”

7. “It might hurt a bit… or it might hurt a lot.”

8. “An ethics committee looked at this study, and they said you should take part.”

9. “No, I didn’t understand that bit either…”

10. Nothing!

CRfocus 20(02) - February 2009

Hollywood goes pharma?

At some time or another, I’m sure all of us has daydreamed about being a film star. But if real film stars decided on a change of career into clinical research, what roles would they end up in?

• Meryl Streep would work in QA, delivering results with precision

• Mickey Rooney would be Operations Manager for a small university biotech spin-off: “Let’s do the show right here!”

• Sigourney Weaver would be an unflappable line manager, nurturing but able to be ruthless if necessary

• Quentin Tarantino would become famous as the fastest implanter of implantable medical devices… often faster and messier than the patients themselves might like!

• Will Smith would be the Project Manager everyone wants on their bid defence team. Joe Pesci would be brought out of retirement to turn round failing studies… or else!

• Wall-E would become a CTA, patiently clearing up the mess left by others before nurturing a study from green shoot to sturdy tree

• Renée Zellweger would be a CRA, doing what it takes to get the job done, before walking off into the sunset

Obama-bandwagon

The International Secret Society of Journalists and Editors (what do you mean you haven’t heard of them?!) has decreed that every newspaper or magazine published in 2009 must include an item or photograph including new US President Barack Obama. While we’ve been assured that he is an avid reader on CRfocus, we’ve yet to source a picture of him with our venerable journal. In the meantime, here is our prediction of what President Obama will accomplish for clinical research. We’ll be generous, and give him his first 100 days in office as a deadline:

• Patients will accurately diagnose themselves and assess the inclusion/exclusion criteria before pro-actively contacting investigation sites to volunteer.

• Data queries will vanish overnight as blood tests and patient-recorded outcomes are replaced by a hand-held ambient full-body scanner. The only drawback is that all doctors will be called “Bones”.

• The FDA will find a new algorithm to dramatically reduce the volume of evidence required to accurately assess a new medicine’s safety and effectiveness. All its decisions will be made within days of submission.

• The general public will realise that they’ve been wrong about the medicines development industry, and we’ll receive a round of applause every time someone takes a tablet or receives an injection.

• Hope will become the most effective placebo of all time, curing all acute conditions, and giving respite from chronic suffering… until the end of his term of office, or at least until the post-election euphoria wears off…

Another Ten Things... not to say in a study planning meeting

1. Is there an attendance list? I’d like to action someone who isn’t here.

2. No, really: I think we could achieve double that recruitment in half the time.

3. Why can’t the first part of the second party be the second part of the first party… or is that the contract for a cross-over study?

4. … and that’s the point in the schedule when we meet to reschedule the rest of the project…

5. We’ve scheduled bloods every week for 6 months; can’t we just take one big sample at the end?

6. Okay, so the investigator who recruits most patients gets to name the drug…

7. We’ll just copy this whole section from the 1986 protocol on this indication…

8. Does taking copies of “ICH GCP for Beginners” to the site initiation meeting count as training?

9. We’ve had a very productive meeting… but this wasn’t it!

10. Nothing!

CRfocus 19(10) - November 2008

Another Ten Things... you wouldn’t want to hear from your sales team

1. We’ve just won another five studies; you can start them all next week, can’t you?

2. If 90% of the target market is adults, why did you do a 3-year paediatric trial?

3. Don’t worry, if it goes wrong we can throw in free ‘rescue management’.

4. We’ve got the contract... but only if the PI’s girlfriend can be in the control group.

5. Why don’t we get tea and biscuits like the CRAs?

6. Don’t worry, by the time we’ve agreed the contract, the patent will have expired!

7. Why can’t we just call the study PRESCRIBEME?

8. You mean I have to sell the pills as well as the mugs and pens!?

9. What do you mean ‘a contract’? We just shook hands on it!

10. Don't think about it, just tell the client you can deliver! 

If financial markets were run by clinical researchers…

• The HMRA (Handling Money Responsibly Agency) would issue guidelines for all to follow.

• CRFs (Credit Repayment Forms) giving every detail of someone’s ability to pay would be filled in and verified against source documents BEFORE they were given a loan.

• The FDAA (Future Debt Acquisition Agency) would campaign to ensure that people understood that “six months’ interest free credit” means that when the sixth months was up they’d be whacked with HUGE interest payments.

• NICE (National Institute for Credit Ethics) would make sure all were treated fairly, and, if not, the UKCRN (UK Credit Reallocation Network) would sort out all communication problems.

• Meanwhile, a trial would be set up where it would be determined whether a good dose of integrity was a complete cure for acute greed.

• In a control group, all bonuses would be taken away, and withdrawal symptoms observed from a distance, but left untreated…

CRfocus 19(09) - October 2008

Another Ten Things... You Wouldn’t Want to See in a File of SOPs

1. SOP for providing covert financial incentives

2. SOP for committing fraud (at least it’s well documented!)

3. SOP for creating a black hole using the Large Hadron Collider particle accelerator (great way to avoid that missed milestone!)

4. SOP on appropriate use of photocopier (71 copies)

5. SOP saying to disregard all other SOPs

6. A used bottle of Tippex

7. The auditor who disappeared 3 months ago

8. A mouse

9. Dust…

10. Nothing!

Olympic fever

As we put together this month’s issue of CRfocus, it seems like every television channel, magazine and website has been full to overflowing with the Olympics. Sadly, there are no Olympic events that are directly related to clinical research… until now!

• Synchronised SDV

• Marathon (AKA completing clinical trial application forms)

• Coxless service provider fours (to see who can really integrate personnel from different providers)

CRfocus 19(08) - September 2008

Another Ten Things... You Wouldn’t Want to Hear at a Regulatory Inspection

1. Of course I allocated patients randomly: I let them choose.

2. I’ve got all the time in the world to chat with you about this little study.

3. Here are the staff I’ve delegated the key tasks to: Roger, Jane and… erm… what was your name again?

4. This is where we keep the milk. Oh, and the IMP as well…

5. Did I say I had data from thirteen patients? OK, wait a minute…

6. But I always use pencil to write up consultations.

7. Well, I ran out of placebo, so I gave them this instead…

8. Yes, that batch of IMP really was eaten by cows. But there was no adverse effect on their milk yield.

9. You’re much nicer than the chaps who did that for-cause inspection last month.

10. What’s an SOP?