Chronology of Events at McMaster University Evidence-Based Clinical Practice Workshop
AtoZ OKAMOTO (Kindai Medical School)

Six Japanese participants sponsored by St.Lukes LifeScience Institute (I am second from right)

Day 0 of McMaster EBCP Workshop
Hi everybody! I am now in LosAngeles and am in the final stage for departure for Hamilton. Hope my flight tomorrow will be a smooth one. It was tough to tackle an almost one inch thick material and I am nervous about how well I can participate. In anyway the die is cast!
Good luck to every participant!
Day 1 at McMaster
The first thing which had come into my sight when the shuttle from the Toronto Airport approached the university campus was a huge, gray colored concrete-made building. "Oh, that is the health science center...." I spoke to myself. Being interested in architecture, I knew since long before the uniqueness of the McMaster university hospital building.
From appearance it looks like a vast, flat building consisting of rectangular boxes. Actually these boxes are building blocks of the entire architecture. The building was constructed simply by binding together these blocks hinged with pillars.
When the building was constructed early 70s, it was highly praised for its flexibility and expandability: building blocks which are similar in size and design can easily be added up when expansion becomes necessary in the future.
The above was nothing more than my personal impression. However I felt that hardware may well reflect software, such as policy and philosophy of the activities practiced inside of it. Flexibility and expandability are the key concepts of what I am going to learn for the 5 days to come. They also characterize the unique educational methods at the university. What is now known as "tutorial" system, which my school is currently endeavering to implement, has become an international norm in medical education.
Checking into the university residence called "Heddin Hall". Since the workshop will officially start on 10th June (tomorrow), I found myself one of a few participants who checked in so early. It is still good to relax enough before the workshop is in full swing. Hope tomorrow morning I will be able to take a walk around on the campus.
Day 2
The 2nd day at McMaster started with struggle over internet connection. According to the manual stating that each room of the university residence is equipped with Ethernet outlet, I brought my lap-top computer with Ethernet cable. However I could not find the outlet in the room. Fortunately a computer technician opened a computer clinic in the residence and kindly instructed how to make it. I found the cable outlet had simply been concealed by the furniture! She also set up the LAN connection in the computer despite all signs were written in Japanese.
Being connected to the world, I spent most of the afternoon time checking Email sent to me in my absence.
At 16:30 the registration started marking the official commencement of the workshop. All participants were given name tags, folders and extra material, then went downstaris for the opening dinner grouped by the designated small group.
After the dinner, each group got together to introduce oneself and discuss the topics to concentrate. After appointing a leader for tomorrow's first small group discussion, the group parted. Each member is expected to prepare a scenario which will fit to his or her educational or research need.
The 2nd day was blessed with nice sunny weather. The temperature went up to the point to make one sweat in day time. The scenary of the campus is too beautiful to stay indoor.
Day 3
The first topic to be discussed was the beneficial effect of acetylcystein on acetaminophen induced fulminant hepatitis.
All participants were given an article of a retrospective study comparing non-treated and treated groups, which showed 21% improvement of survival. Althugh the methodology was not randomized, the comparative profile between the two groups seemed to me convincing enough about the validity of the result.
However participants responsible for presentation presented yet another article written by the same author and published in BMJ (the other one was Lancet) only one year later. This one was RCT but not blinded to provider because of "pungent aroma" of acetylcystein, which showed 28% improvement of survival.
This indicates how much the rigor of methodology is emphasized in EBM. The author had to conduct a RCT even though they were reasonably certain about the superior nature of acetylcystein. Howver I could not help wondering if such seemingly "redundant" RCT is warranted in view of ethics. The 50 patient were assigned to either treatment arm or non treatment arm. 28% difference of survival translates into nearly 10 patients who could have been saved if they had been given treatment from the beginning.
Although the RCT was approved by ethics committee, some doubts remain. Also, the author calculated the number of sample size as 25 to detect 40% difference of survival at 5% alpha error and 20% beta error. Strangely enough the author concluded that a significant difference had been detected despite the revealed difference was 28%.
This remains mystery to me.
Day 4 CDR(Clinical Decision Rule)
Diagnostic test may be best used when it is conducted on well targetted patients population. Clinical Decision Rule (CDR) is a rule of thumb to yield a best predictive value for the test.
On Day4 we discussed on CDR using osteoporosis screening test (DXA). Development of CDR consists of three phases: devivation, validation and impact analysis. A well designed study in Canada, Ontario produced a good CDR called ORAI. This enables doctors to identify the best candidates for DXA test just by examining three attributes of the patients:age, weight and estrogen use.
The study was conducted as part of Canadian Osteoporosis study, in which 926 were allocated for development group and the rest for validating the CDR.
The author claim that by applying ORAI, as much as 38% of DXA test would be avoided without much sacrificing the chance of overlooking osteoporosis.
Validity was ascertained by applying the CDR to the randomly selected subgroup from the same population thereby limiting its generalizability. Actually 94% of the participants were white and may not be applicable to, say, Baltimore (nearly half of the residents are nonwhite) or Japan.
This indicates a serious need for Japan to develop its own version of CDR. Also for CDR to be effectively imprelemented, incentives such as economic incentives should be given to doctors. A study I am currently involved is to develop criteria for insurers to evaluate performance of hospitals. One of the criteria is predictive value of diagnostic tests. CDR is a good tool to maximize the predictive value of tests and would be needed by hospitals when they are demanded to increase the predictive value of any diagnostic tests.
Day 5 Alarmed FDA Panel
In every small group discussion, each participant will be assigned as a moderater with a chosen topic.
I was assigned for the role in the morning of the 5th day. The assigned topis is "Phenypropanolamine(PPA) and cerebral hemorrhage", a hot topic which lead to withdrawal of the product from the U.S. at the and of 2000.
PPA is commonly contained in cold medicines or nasal decongestant available over the counter, such as "Contac" or "Dan Rich" in Japan. It has been in market since the 1960s, but has been suspected of its potential link with rare but serious ADR of cerebral hemorrhage. However because of its rareness, it has not been fully investigated.
As is usual with small group discussions, it is done by way of role playing usually mimicking a doctor and a patient. This time I produced that the entire member play as FDA expert panel members with myself as a commissioner.
The scenario is that FDA was faced with sporadic case reports from Taiwan on a young woman who suffered a stroke after injesting PPA containinig capsules. The alarmed commissioner summoned panel experts to discuss whether they should or should not take any actions, and what actions.
After discussion the pharmacological nature of PPA, we obtained a RCT conducted in the U.S. ten years ago, which demonstrated no hypertensive effect of PPA. After discussing the content of the RCT we learned that RCT, though widely perceived as methodologically superior, may not be an appropriate method to detect such a rare ADR as strokes.
We then nagigated toward another method known as a case-control study. We further discussed about how the study should be designed particularly with respect to selection of controls.
It was technically tough challenge to understand the details of the study published in NEJM in Dec 2000. However all participants were deeply impressed at the rigor with which the study had been conducted: On average 151 telephone calls were made to find an appropriate controls for every cases identified with objective criteria.
When we were ready to discuss on the action taken by FDA we almost ran out of time. We discussed on the two commentaries submitted by pharmacists who challenged the FDA action to demand manufacturers to withdraw all PPA containing products for both cold medicines and appetite suppressant. It is also interesting to note that the UK and Japanese governments did not follow FDA while the Canadian government followed suit.
Whether geographical proximity played any role resulting in the difference of actions could not be concluded.
Day 6 CPG and Critical Pathways
The final day of the workshop was on the CPG and Critical Pathways. Those are the tools which will standardize the complex care of the patients and thereby achieving better quality of care. Interestingly enough, when the moderator took a vote on whether participants would agree with this assertion, the response was mixed: about half of us agreed that implementing CPG and Critical Pathways would lead to improvement of care, about the same number dimurred. One participant stated that patients' condition are to complex to be standardized.
The particular topic for the day was on the CPG on heart failure. When the discussion moved onto beta blocker usage, which is still contraindicated in Japan, one pointed out that nearly 80% of prescription are "off lable" prescription. It is a contradiction that a drug contraindicated on label are encouraged in EBM. Quite a red tape!
The entire workshop was concluded by a plenary session with a concluding remark by Dr. Guyatt. All six Japanese participants took pictures to commemorate this valuable and unforgettable workshop.
All of us now feel confident and obliged to bring back what we have learned during this intense 6 days workshop. Great thanks and good bye!