Category: Product Review, Polarity of "ActiBiphasic" waveform.
From advertising material, as well as operating and service manuals of CardioLife Acti-Biphasic
defibrillators, we know the declared Acti-Biphasic waveform looks like what is shown in below picture. This is also the waveform submitted to obtain regulatory approvals around the world, supported by a Certificate of Free Sales from Japanese regulatory authority, MHLW and/or CE Certification.
| The ACTI-BIPHASIC discharge output declared by the manufacturer |
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| Declared characteristics of the Acti-Biphasic discharge waveform in advertising, operator and service manuals |
| The basic concept of a bi-phasic shock energy is to add a negative follow-up phase to the conventional mono-phasic shock to achieve the same defibrillation result using lesser energy |
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The characteristics of NIHON KOHDEN Acti-Biphasic defibrillation can be summarized as:
1. First (Launch) Phase
The Acti-Biphasic waveform is seen as operating in an open loop during the first phase (period).
- It is a positive truncated exponential pulse with a duration depending on the patient impedance.
- It is of a longer duration than the second period.
- It is of a longer duration than the second period.
2. Second (Follow-up) Phase
The Acti-Biphasic waveform operates in a closed loop
during the second phase. In a closed loop the duration of the width can be deliberately set to a specific duration.
- This second phase (period) is shorter in duration and of negative polarity.
- The duration in this phase is fixed to a constant 3.4ms duration regardless of patient impedance. How was the optimal duration of 3.4ms arrived at? It is also not clear how was the maximum energy of 270 Joules concluded?
- The duration in this phase is fixed to a constant 3.4ms duration regardless of patient impedance. How was the optimal duration of 3.4ms arrived at? It is also not clear how was the maximum energy of 270 Joules concluded?
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| Note the first phase (period) is positive and a wider pulse than the second phase |
| The first to use Acti-Biphasic waveform were the CardioLife TEC-7700K series defibrillators |
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The
CardioLife TEC-7000 series defibrillators had two models, the
CardioLife TEC-7721K and CardioLife TEC-7731K (built-in pacing unit).
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| The first Acti-Biphasic defibrillators |
| Output discharged by CardioLife TEC-7700K series defibrillators is consistent with the declared waveform |
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The
discharge waveform of the CardioLife TEC-7700K series on a strip chart is as
shown below. The recording correctly reflects the first phase as a positive pulse.
The recording shows the voltage first swings to the top (positive saturation), then to negative saturation after some time; this is fully consistent with the official description of the Acti-Biphasic waveform.
The
reason we are not seeing the full shape of the Acti-Biphasic waveform
on the recording is because the sensitivity is set to see the smaller
ECG waveform, and not the defibrillation shock which are much higher in
magnitude.
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| This strip chart recording shows output of CardioLife TEC-7700K series is consistent with the declared description |
| How can we know if the Acti-Biphasic defibrillation shock actually works on patients? |
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| The margin of error is high for data from a small 75 investigated cases |
There is no white paper available. The Acti-Biphasic defibrillators were hurriedly launched (for export) before completion of proper clinical validation and the small sample size of seventy five investigated cases meant a high margin of error; we
cannot be sure the Acti-Biphasic defibrillation shock works on
patients! In addition, how can we be absolutely sure the investigated
cases were done in an acceptable manner?
As the mono-phasic defibrillators are not predicate devices so the FDA 510(K) process cannot be used to clear the product for sales in the US market. Since the clinical data and methodology adopted by NIHON KOHDEN fell short of US FDA guide for safety and effectiveness,
the Acti-Biphasic defibrillation shock is not allowed for sales in the US market; Nihon Kohden could have engaged a consultant to
ensure a proper and acceptable clinical validation process if they had
wanted to do it right. This implies the design is not yet good for use,
and further improvements are needed for it to meet US FDA requirements.
It
is necessary here to clarify that current CE certification does not
guarantee clinical performance since clinical validation is not
included. This means you need clinical papers in addition to CE
certification.
The persistent remarks
we often heard from NIHON KOHDEN marketing staff on American Heart
Association recommendations are in reality, meaningless to Acti-Biphasic
defibrillators.
Outside
of the US market, we need to question the point of buying such critical
treatment devices and placing them on standby to save lives? Remember,
compliance to just safety standards is no guarantee of performance! It is so unfair to the patients needing immediate treatment in a life-threatening situation!
| Biphasic defibrillation was a nightmare, one that caught NIHON KOHDEN development team off guard |
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In May 1997 Nihon Kohden released a new defibrillator with a semi-automatic AED mode for export using mono-phasic defibrillation. The details of this TEC-2200K series can be found in the 1997 Product Guide.
This
was
a mono-phasic model using the non-proprietary Edmark single-phase pulse
as illustrated and the use of rechargeable battery for energy made it
very inconvenient for public use.
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| Edwark, Single Phase Pulse defibrillation waveform used by monophasic CardioLife TEC-2200K series in 1997 |
The monophasic output discharge waveform shape is shown below. Note
its shape as we will later show "Acti-Biphasic" AED-2100K, AED-2150K,
AED-2152K and AED-3100 automated external defibrillators all discharge
the same monophasic energy.
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| CardioLife TEC-2200K mono-phasic output waveform recorded on a strip chart dated April 1995 |
Just a few months after the
TEC-2200 series was released, then market leader Hewlett Packard made announcement to acquire Heartstream Inc.
in a stock-swap deal.
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| Heartstream ForeRunner |
Biphasic defibrillation waveform was becoming the new preference
as it allowed for a smaller and lighter defibrillator design; more importantly
it uses less current and this means less damage defibrillation will do to the
heart and skin. The deal with Heartstream
was how the then defibrillator market leader HP acquired biphasic
technology, since to develop one would take time and speed to market was
a top priority.
With a changing trend in the international market, there
was therefore zero interest in the monophasic TEC-2200 series
defibrillators offered by Nihon Kohden for ex-Japan market and the products had to be withdrawn from exporting.
Unlike
the monophasic pulse, biphasic waveform comes in various forms; each
type of shape is proprietary and
cannot be copied freely. This means the energy envelopes of
manufacturers in the market are all
different. For some waveform, the manufacturers only recommend a maximum
of 200
joules while another can recommend energy as high as 360 joules. All
manufacturers must therefore justify the use of their proprietary output
waveform in some reasonable ways, preferably in
accordance with US FDA guide for safety and effectiveness, which calls
for clinical research validations or the manufacturers should at least cite published clinical papers which had been properly subjected to peer review.
| NIHON KOHDEN was further thrown off balance by the speed of global shift to biphasic technology |
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It
was a market disruption that NIHON KOHDEN was unprepared for. The
company was at a loss for the next four years how to obtain the
technology to offer biphasic defibrillators; this means the company's
defibrillator development team was helpless in the face of disruption
from changing technology. It was obvious to any observer they could only
solve the problem by buying the technology from someone.
When the
demand for biphasic AEDs eventually emerged in the Japanese domestic
market, the company resorted to find a suitable partner with biphasic
technology for co-operation. A strategic OEM distribution agreement was announced in January 2002 that Nihon Kohden would market Cardiac Science's line of AEDs under Nihon Kohden's
trade name. This arrangement was a big success and many AED-9200 and AED-9231 were
sold in Japan as reflected in annual reports and presentations.
Mark
the date January 2002, and subsequent release of first Acti-Biphasic
defibrillators (CardioLife TEC-7700 series) by NIHON KOHDEN in November
2002.
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| NIHON KOHDEN CardioLife AED-9200 and AED-9231 were highlighted to have very good sales in FY2006 financial results presentation |
| The Cardiac Science STAR biphasic waveform was validated by researchers at Cleveland Clinic and Cedars-Sinai Medical Center in accordance with US FDA guides for Safety and Effectiveness |
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The
success of the STAR biphasic shock in the domestic market however,
could not be replicated for exports to foreign markets since
distributors could buy the original models at much cheaper prices from
Cardiac Science directly.
To our surprise, instead of licensing the proprietary biphasic defibrillation design from Cardiac Science, a few engineers in NIHON KOHDEN could suddenly conclude a workable, proprietary Acti-Biphasic shock waveform just by playing with biphasic circuitry on pigs with minimal clinical supervision and collaboration, it is no wonder that the company had great difficulty securing the necessary clinical support to advance the number of investigated cases for proper clinical validation. To date, there is not a single clinical paper published on Acti-Biphasic defibrillation.
| Customers were sold unproven defibrillators and the absence of internal safeguards |
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Before completion of proper clinical validations, the company was bold enough to go ahead with exporting the unproven TEC-7700 series Acti-Biphasic defibrillators from November 2002, taking advantage of its established distribution network for mono-phasic
defibrillators. The customers were sold unproven defibrillators by taking advantage of their good faith, because there was no published clinical paper to show that it works. This November 2002
export launch was three long years ahead of the date Japan MHLW
officially approved its use for the domestic market.
The desperate action was taken in response to the rapid changing preference for biphasic defibrillators in the market but the process totally overlooked the seriousness of mandatory successful clinical studies before marketing; the fact that Ministry of Health, Labour and Welfare (MHLW)
had not yet approved the sales of TEC-7700 series defibrillators in
Japan domestic market reflected the disturbing absence of internal safeguards in
corporate conduct.
Up to this point, the company had never exported a
new product before first
launching it in
Japan, showing the company was in complete disarray. It
is not just loss of credibility in overseas markets as a leading defibrillator
exporter from Japan but a ticking time bomb
with important
issues left unattended.
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| Nihon Kohden began exporting unproven proprietary Acti-Biphasic defibrillators in 2002 |
| Japanese Regulatory Authority took three long years to grant sales approval for the TEC-7700 series defibrillators in Japan |
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This meant the application was turned down several times and serious
doubts by the Regulatory Authority to grant its use. What prompted the
decision to clear it after three years' wait is something we should
know, is the manufacturer willing to share the fact? By the time of receiving approval to sell in Japan, many CardioLife TEC-7700 series defibrillators were already exported.
NIHON KOHDEN was only able to announce the launch of TEC-7700 series defibrillators for sales in
Japan market on December 1st, 2005.
| Did NIHON KOHDEN give up the original Acti-Biphasic defibrillation output waveform? |
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Nihon Kohden incredibly launched another unproven
Acti-Biphasic TEC-5500 series defibrillators for
export sales in August 2004, more than a year before the above announcement; it was as if the two are unrelated. The
urgent launch of TEC-5500 series defibrillators for export did not make
sense, the event sent a subtle message something fundamental had changed.
We were therefore not surprised to later find the waveform discharged by the TEC-5500 series defibrillators different from the TEC-7700K series defibrillators. It is a version that is flipped vertically upside down from that of the TEC-7700 series defibrillators! The
change in the shape of the waveform was not officially announced at the
time of launch, it was only discovered later by accident in the field.
Was
the manufacturer under pressure to stop using the declared discharge
waveform (that is still currently being published on the service and
operator manuals)?
This was
happening prior to Japan MHLW approval for the TEC-7700 series, and without showing any clinical evidence to support its use!
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| Dubious CardioLife TEC-5500K series started to be exported from August 2004, when Japan MHLW had not approved the sales of CardioLife TEC-7700 series |
| The Timeline |
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| Export of dubious CardioLife TEC-5500K series started in August 2004, more than one year before Japan MHLW actually approved the TEC-7700 series |
CardioLife
TEC-5500 series defibrillators were quickly approved for sales in Japan
after the approval was given for CardioLife TEC-7700 series, based on
the principle of declared substantial equivalence with the
newly-approved TEC-7700 series. In Japan, the Acti-biphasic waveform
discharged by Japanese version TEC-5500 series defibrillators is
unlikely to be different from that discharged by TEC-7700 series
defibrillators.
However,
the export models of the TEC-5500 series, TEC-5600 series and TEC-8300
series defibrillators were all found to have their discharged waveform
inverted, but submission documents to foreign regulatory authorities
were all based on the TEC-7700 series. Are these regulatory approvals valid?
| A top prestigious University Hospital in Taiwan |
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