Academic Report On The Pitfalls Of Clinical Trial For Medical Devices

Academic Report On The Pitfalls Of Clinical Trial For Medical Devices
1.0 BACKGROUND OF THE REPORT
The author has based on the case study known as the Blinded Evaluation of Laser Intervention Electively For
Angina Pectoris (BELIEF) trial reported by Nordrehaug and Fauls (1999). Case name is known as A
Randomized, Sham-Procedure-Controlled Trial of Percutaneous Myocardial Laser Therapy (PML)
1.1 BACKGROUND OF THE CLINICAL TRIAL
There are a majority of patients at a growing rate who have medically refractory angina caused by diffuse
coronary artery disease who are not suitable for percutaneous coronary intervention (PCI) or coronary artery
bypass graft surgery (CABG). Prior to the development of the surgical transmyocardial laser revascularization,
treatment option are limited to this subset of patients.
Prior to the year 1995, the Norwegian Ministry of Health (NMOH) prohibited the use of the surgical
transmyocardial laser revascularization (TMR) as a routine clinical option cited the concerns regarding the
procedural morbidity and mortality.
Only in year 1999, an independent expert consensus panel of cardiothoracic surgeons, cardiologists, and
physiologist commissioned by The Norwegian Ministry of Health (NMOH) went through an extensive review
of the non-clinical and clinical literature to revisit the feasibility, suitability and acceptability of surgical
transmyocardial laser revascularization (TMR) procedure that was banned since 1995.
The panel eventually concluded that transmyocardial laser revascularization (TMR) consistently provides
significant symptomatic relief and lifted the ban on prohibiting surgical transmyocardial laser revascularization
(TMR) as a routine clinical option for patients with severe angina.
However, the panel couldn’t figure out the mechanism for transmyocardial laser revascularization (TMR) on
how it delivered its clinical benefits. This unknown mechanism together with the lack of evidence discounting
the placebo effect as the primary mechanism for the observed clinical improvement still limited the routine
clinical use of the technology.
1.2 OBJECTIVES OF BELIEF TRIAL
To address the panel’s finding and to workaround the unethical practice of a Sham transmyocardial laser
revascularization (TMR) trial. Nordrehaug and Fauls (1999) designed the BELIEF clinical trial as a randomized,
two-arms, double-blind clinical trial to control for patient bias (the placebo effect) and investigator bias
(assessment bias) in determining the clinical benefit of Percutaneous Myocardial Laser (PML) treatment.
A sample size of minimum 82 patients that have to be randomized into comparable key baseline characteristics
were established to detect a clinically relevant difference in the proportion of patients with at least a one class
improvement in Canadian Cardiovascular Society grading (CCS) angina class. All assessment were conducted
by blinded, independent assessors.
1.3 PARTICIPATING STAKEHOLDERS
All aspects of the BELIEF trial were conducted in Norway with the participation of Haukeland University
Hospital and Ullevaal University Hospital. The trial were conducted under the governance of the Institutional
Ethics Review Committees and according to the guideline set forth in the Declaration of Helsinki.
The Biostatistic Department of the University of Bergen assisted in generating of the randomization code for the
procedural blinding and randomization process.
Funding for the BELIEF trial was provided through a grant from the Bergen Norway Heart Foundation.
EdwinNgChunPeng_RAPS_Module 2_Term Report_2015_2016 pg. 1

The CardioGenesis Corporation’s Axcis PML system was chosen for the BELIEF trial because of its proven
clinical benefits in a randomized, controlled, open-label trial.
1.4 PROCEDURAL DETAILS
The Axcis PML system consists of the holmium:yttrium-aluminum-garnet laser, an electrocardiography (ECG)
monitor, and the sterile delivery system. The laser is a portable, self-contained unit that has a maximum
therapeutic output of 6W and consists of a laser console and a footswitch.
The limitation of the Axcis PML system is the continuous output of the laser energy that penetrates the tissue to
a depth of around 5 to 6cm even though the physical penetration has stopped. As a result, clinical application is
limited to eligible areas of the left ventricular wall that are at least 8mm thick to reduce the potential for
pericardial perforation.
In the PML group, pulsed-laser energy was delivered to the endocardium through the laser catheter to create a
nontransmural channel. For the Sham group, the procedure (invasive) was identical except that there was no
laser energy delivered to the patient when the interventionalist activated the footswitch.
1.5 PROCEDURAL METHODS
A total of eighty-two qualified patients with severe angina (20 PML and 42 Sham) undergo the trial. The PML
group were assigned to receive Myocardial Laser channels, pulsed laser energy was delivered to the
endocardium through the laser catheter to create a nontransmural channel. For the Sham group, they were
subjected to the blinded Sham procedure (known as placebo) that was identical except there was no laser energy
delivered.
All patients were in Canadian Cardiovascular Society grading (CCS) Class III or IV at baseline, with
distributions comparable between group.
The primary endpoint was the change in Canadian Cardiovascular Society grading (CCS) angina class from 3-
months, 6-months, and a 1-year angina class assessment.
1.6 RESULTS
79 out of the 82 patients randomized were available for follow-up through 1 year.
There were no crossover of patients from the Sham group to the treated group, no withdrawals and none of the
patients received additional revascularization procedures and change of medication during the study.
Results through 1 year of Mean angina class improvement at 3 months, angina class improved to 2.3 +- 1.0 in
the PML group and to 2.7 +- 0.9 in the Sham group.
At 6 months, Angina class was reduced significantly more in the PML group at 2.0+- 1.1 as compared to the
Sham group at 2.7+- 0.9. The PML group were observed to have improved by at least 1 class (63% vs. 36%)
and by at least 2 classes (40% vs. 12%) from baseline.
At the 1 year assessment, the trend continued for the PML group, one or more class improvement (63% vs.
38%) over the Sham group and two or more class improvement (35% vs. 14%) over the Sham group.
The procedural success, in this case, study was defined as the completion of the entire procedure through patient
discharge in the absent of death or perforation.
At 1 year, cardiac event-free survival as defined as the absence of death, MI, perforation, stroke/TIA and angina
requiring rehospitalization was similar between groups. In the PML group, there were no death or MI, only a
case of single perforation, a patient suffered a stroke at 3 months and was unable to travel for further follow-ups
and three other patients were hospitalized for angina during follow-up.

On the other hand, in the Sham group, 2 patients deaths occurred, one procedurally and the other at 3 months
owing to a suspected MI. 1 patient was reported with MI, TIA, and atrial fibrillation. 3 other patients were
hospitalized for angina during follow-up.
1.7 CONCLUSION FROM BELIEF TRIAL
Nordrehaug and Fauls (1999) concluded their unique design, well-focused and excellent follow-up randomized,
double-blind, Sham-controlled BELIEF trial mitigated the influence of other potentially confounding factors
such as changes in medical therapy or incomplete ascertainment.
As a result, the positive 1-year results are free from any concern of placebo effect as a primary mechanism.
Together with the superior Axcis PML system intended to achieve the stated primary endpoint. The clinical
benefit is indeed attributed to the effect of treatment and beyond placebo.
2.0 DISCUSSION ON THE PITFALLS OF BELIEF TRIAL
The BELIEF trial is in the opinion of the author a first and foremost new trial and therapy in the year 1996
without any precedent case for reference and to improvise. However, Nordrehaug and Fauls were capable
enough to design and implemented the trial while adhering to the regulation and expectation of the many
different stakeholders and opinion leaders namely: the Norwegian Ministry of Health (NMOH), CardioGenesis
Corporation, Bergen Norway Heart Foundation, The Ethics Review Committees of both Haukeland University
Hospital and Ullevaal University Hospital.
For that reason, the author’s purpose of this paper is not to criticize but to raise more questions, suggest
recommendation and to provide some corresponding answer from the finding in the various referencing source.
The following statements on the pitfalls of the BELIEF trial are based on observation by the author based on
others case-study and are not conclusively in nature.
2.1 UNINTENTIONALLY DISCLOSURE
In this BELIEF trial, to assure blinding of the patients, there was great effort to conceal the laser console and the
laser operator by placing them behind an opaque curtain out of view in the cardiac catheterization laboratory.
Furthermore, music was played during the procedure to mask over the audible feedback from the laser system
that could reveal the randomized assignment.
The author believed that the laser inducing smell and even surgical smoke will be observed by the treating
investigators, staffs and PML group participants, whereas for Sham group participants it is the lack of smell and
smoke. Cooper et al. (2014) commented that trial participants can comments, share and feedback on the
different characteristics of the intervention among treating investigators and others participants which may
eventually reveal the group allocation.
The author believed that by maintaining a Confidential Disclosure Agreement (CDA) or Non-Disclosure
Agreement (NDA) among all parties should be able to address the revelation pitfall and at least minimize the
chances of occurring.
2.2 SHORT-TERM RELIEF?
Galiñanes, et al. (2004) reported PML treatment is an effective short-term therapy for the relief of angina and
the improvement of the quality of life of patients with diffuse coronary artery disease who cannot receive
angioplasty or bypass graft surgery. However, its efficacy is limited and most patients remain with some degree
of angina. This clinical benefit is partly lost by 42 months follow-up suggesting that the improvement may be
transient.

Based on the finding above, the author finds that the Norwegian Ministry of Health (NMOH) expert consensus
panel should have also included clinical questions such as how the duration, frequency and number of follow-up
will affect and impact on the assessment of a longer-term clinical benefit for the BELIEF trial to address.
2.3 DIFFERENT STARTING LINE = DIFFERENT RESULT?
Based on the BELIEF finding, both of the PML group and Sham group actually observed a reduction in Angina
class and improvement by at least one class or by at least two classes (albeit in different ratio) which the PML
group can claim superiority because there were more successfully cases.
However, the author finds that there are actually different baseline characteristics in the randomized group. In
other words, both of the PML group and Sham group are not segmented according to same considerable health
status. For example, in the table shown on page 9 extracted from BELIEF trial, the Sham group have more
patients with a history of diabetes mellitus, systemic hypertension, myocardial infarction and even the history of
smoking.
Will this unbalance randomized group affect the studies? Has the unbalanced group contributed more adverse
events (including 2 patients’ deaths) in the Sham group than the PML group? Looking at the all-cause mortality
at 1 year with the PML group at 0% compared to the Sham group at 5%, why was the mortality rate loop sided
to the advantage of the PML group.
All this are questions that the author believes is important for future similar trial. The pitfall of BELIEF trial in
this aspect is that it does not explicitly answer in the finding and report. There was no mention of how
professional medical personnel interview and assess each and every participating patients on their actual health
condition whether they are fit to undergo the treatments.
The best practice is to design a trial that looks at each and individual health assessment in robust ways before
determining the selection of the randomized group. Looking into the details of every patient are crucial in which
Haynes and Haines (1998) have reported practitioner must interview and assess if the patient has any other
problems that might influence the decision of clinical trial treatment. For example, patients must be physically
fit enough to have invasive surgery.

2.4 NOT EUROPEAN UNION (EU) AND FDA APPROVED?
In this BELIEF trial, there was no mentioned of any compliance to Clinical investigation plan (CIP).
Furthermore, there was no report of the adherence of preparing the CIP in accordance with ISO 14155:2011
Clinical investigation of medical devices for human subjects – Good clinical practice.
The pitfall and omission will not ensure BELIEF trial to be compliance with EU regulation on clinical
investigation of the medical device. Furthermore, Saririan and Eisenberg (2003) reported Percutaneous
myocardial laser revascularization (PML) appears to be associated with less morbidity than Transmyocardial
laser revascularization (TMR) but the PML technique is still considered investigational and is not FDA
approved.
The author believes the design of the BELIEF trial was focused more on the device whether it is shown to be
safe in bench and in vivo testing with significant clinical benefits that have received or under evaluation for
European authorization. Conversely, there was lesser emphasis on fulfilling the Clinical investigation plan.
The author suggests that although Norway not a member state of the European Union (EU), it maintains
membership in the European Economic Area (EEA), in the context of being a European Free Trade Association
(EFTA) member.
The design of the BELIEF trial should consider consulting the EU Clinical Trials Register on the protocol prior
to execution.
This is imperative as the BELIEF trial were executed, study and follow up together with medical therapy.
Furthermore, EU Clinical Trials Register (No date) is an official database containing the guidelines and
requirements of conducing clinical trial with investigator sites in both of the EU and or EEA.
2.5 PRIMARY MECHANISM STILL UNKNOWN?
This BELIEF trial reasoned that there were other five independently conducted, randomized controlled trials of
TMR as sole therapy (1 year result) shown significantly consistent improvement in angina symptoms, quality of
life, and cardiac event-free survival. As a result, the design of the BELIEF trial is perceived to be ethically
allowable.
In this regard, the author does not agree that the precedent five trials are comparable on an equal footing because
the design, equipment, methods and consideration are all different. Therefore, more emphasis has to be placed in
the various clinical trial phases.
Especially Michael (1999) commented all Transmyocardial revascularization (TMR) have not addressed the
issue of mechanism of any benefit, it can be a cause and effect of opening the channels to stay open and create a
reptilian heart with sinusoids for perfusion of the myocardium and even denervation may be the mechanism.
The author suggests holding a 4 phases clinical trial namely: phase 1- test out the treatment to evaluate its
safety, determine a safe dosage range and to identify side effects.
Phase 2- test out the treatment to a larger group of people to assess the effectiveness and to further evaluate its
safety.
Phase 3- test out the treatment to an even larger group to confirm its effectiveness, monitor side effects,
compile, compare and contrast all information to further allow the treatment to be used safely.
Phase 4- After acceptance in more countries to carry out the treatment, to gather information on the treatment
effect in various populations and any side effects associated with long-term use.

2.6 IS BELIEF TRIAL MORE THAN A CASE STUDY?
Kramer and Cutlip (2015) championed that pivotal studies leading to regulatory approval of high-risk
cardiovascular devices should be made available in the peer-reviewed literature especially when these devices
constitute practice-changing therapies.
The author also strongly agrees that it is a must to disclose and distribute as much useful information and
finding as secondary data/information in order to help advanced the technique and technology on a wider global
platform.
The author suspected that the BELIEF trial case study cannot be considered as a peer-reviewed literature
because firstly it cannot be searched as a journal paper from various public-domain libraries resources including
the National University of Singapore (NUS) library journal articles database.
Secondly, the BELIEF trial was actually a case studies published by Becker, K.M. & Whyte, J.J. (2006) in the
book known as a Clinical evaluation of medical devices: principles and case studies.
Thirdly, even though the BELIEF trial case mentioned about the funding for the trial was provided through a
grant from the Bergen Norway Heart Foundation and none of the treating investigators had any financial interest
in the manufacturer of the investigational device. Conversely, there was no disclosure statements from the
writer (Nordrehaug and Faul) to prevent any compromise arising from undeclared financial support or other
benefits.
In order for practitioners to make informed clinical decisions for future similar treatment, rather than relying
only on peer-reviewed literature. The author suggests any future clinical trial to be published in both of the EU
Clinical Trials Register (No date) [A service of European Medicines Agency] and ClinicalTrials.gov (2015) [A
service of the U.S. National Institutes of Health].
Both of this platform provides patients, their family members, health care professionals, researchers, and the
public with easy access to information on publicly and privately supported clinical studies
2.7 MONETARY OR INTRINSIC MOTIVATION?
Science Letter editors (2008) reported monetary reward to participation in clinical trial study will affect their
willingness to participate compared to no monetary reward. Based on the above finding, the author find the
BELIEF trial not offering any form of compensation to the
participating patients was not patient-friendly because since the no-option angina patients are less likely to be
drawn by the financial incentives, but by offering gesture of goodwill token sum of money for participation
seemed to be humanely and morally right to do so in the author point of view.
Conversely, there was no record of finding to show how many eligible patients actually opt out because of the
lack of monetary compensation. This is a question worth investigating because the BELIEF trial was actually
conducted in a multi-centres setting, firstly, Haukeland University Hospital (Bergen, Norway) and secondly,
Ullevääl University Hospital (Oslo, Norway). Either location will require a considerable amount of time, effort,
and money to travel to and return.
2.8 RIGHT VS REGULATION
The BELIEF trial is fully aware of the red-tape and acted diligently in complying with the regulation needs. No
doubt it had complied with the various regulation and ethical bodies. Furthermore, it was perceived to be
successfully in term of the design and conduct of the trial, there was no major error in term of randomization,
concealment, and blinding and data collection.
However, the author would like to see from the perspective of the Sham group. The glaring point from the
BELIEF trial was that patients were only notified of their randomized assignments into PML group and Sham
group after the 1-year follow-up.
The author believes the higher purpose of the BELIEF trial is to investigate the “right treatment” for the no-
option angina patients.

On the other hand, the author strongly argues that the Sham group have every right to be exposed to “real”
treatment same as what the PML group of patients received.
Therefore to address this pitfall, the author recommends the BELIEF trial to be designed as a cross-over type,
allowing both PML group and Sham group to be assessed from the two aspects. By allowing cross-over, both of
the PML group and Sham group will not be denied the right to be treated.
On the other hand, Bridges, et al. (2006) reported severity angina patients with only sole-therapy PML treatment
experience early morbidity, the author believes that the BELIEF trial should have also taken care of the patient’s
drug management seriously because there were no dose changes in any cardiovascular medication through the 1
year. Was it by design or by situation?
2.9 MAN VS WOMEN
In this BELIEF trial, there were only 2 women (5%) in the PML group and 5 women (12%) in the Sham group.
The author believed the ratio is not proportionally distributed to run the trial as man and women have different
epidemiological characteristics. Redberg and Dhruva (2012) goes to the extent to report that women have higher
procedural morbidity and mortality than men during many invasive medical devices procedures.
In order to overcome this pitfall and to further investigate the effects of gender-specific safety and effectiveness
assessment, the author suggests designing clinical trials that focus on men only or women only or equal sample
size between man and women.
2.9.1 PLACEBO EFFECT ON BOTH PLACEBO AND NON-PLACEBO GROUP
As noted by Nordrehaug and Fauls (1996) the BELIEF clinical trial was designed as a randomized, two-arms,
double-blind clinical trial to control for patient bias (the placebo effect) and investigator bias in determining the
clinical benefit of Percutaneous Myocardial Laser (PML) treatment.
Credit must be given to Nordrehaug and Fauls for designing a trial to consider and covered all possible angle to
control for patient bias (the placebo effect). This sentiment was also echoed by Howick (2008) who concluded
that keeping trials successfully double-masked is extremely difficult.
Conversely, there is no perfect fool proof plan. Roy (2012) argues any patient receiving an active treatment
might also have falsely believe that they are receiving the placebo or Sham therapy. Granger and Gersh (2015)
also argues that even when the patients have been effectively kept unaware of the study assignment, both of the
placebo and non-placebo group patients still would believe that they have received the same active treatment.
Bonetti, et al. (2003) commented that the mechanism of action of PML laser therapy in most multiple
randomized trials have failed to demonstrate an increase in survival and most of the trial are not fully able to
explain the placebo effect. Further and longer-term trial and research are needed to elucidate the value of PML
treatment. In conclusion, there may not be 100% control for patient bias among the PML group and Sham
group!
Upholding all of the above argument, the author strongly agrees that the placebo effect would also have
influence patients who are receiving the active treatment to lead to more “feel good” effect and that may explain
the improvement in Canadian Cardiovascular Society grading (CCS) angina class for the PML group as
compared to the Sham group.
A longer study with cross over of patients will be crucial to address the above pitfalls. There is also a need to
look beyond the one-year clinical benefits so as to assess the patient’s after-treatment holistically. The author
suggests for future similar trial to have a post-assessment check-up for the patients every year for a five years
recording periods.

2.9.2 INFORMED CONSENT = INFORMED RISK?
The BELIEF trial reported that patients were issues with written informed consent prior to the treatment.
Despite advances in PML treatment and patient management, the author believes any identified risk must be
fully disclosed to the patient, on top of written informed consent, any associated risks have to be communicated
to the patients. Robinson and Cook (2006) champion that the highest priority in any clinical trial is the
protection of research subjects and patients from any injury.
As a result, the author believes the BELIEF clinical trial design should be focusing more on the risk
management for the investigational device that consists of two catheters dual system and its limitation during
the clinical application that will still allow laser energy to continue to penetrate the tissue to a depth of around 5
to 6cm.
The risk management finding, limitation, control methods and the reason for requiring patients to have at least 8
mm thick of the left ventricular wall so as to reduce the potential for pericardial perforation have to be clearly
communicated to patients on top of the necessary informed consent.
The author suggests the BELIEF to implement the EN ISO 14971 Risk Management for Medical Devices and
ICH Harmonised Tripartite Guideline Q9 for Quality Risk Management both for clinical trial risk management.
This is important because throughout this BELIEF trial, only one individual participating in the procedures, the
laser operator, was aware of the randomized assignments.
In the author point of view, there was no 2nd
opinion, supervision, and control while the laser operator acted to
power on or power off the lead box that transmits laser after reading the treatment assignment envelope. There
are many possible risk factors such as mix-up of the envelope, misinterpretation of the envelope content, simple
human-prone mistake by pressing/executing wrongly and even act of sabotaging and many others issues.
3.0 CONCLUSION BY THE AUTHOR
The author would like to conclude this term paper by discussing on the suitability, feasibility and acceptability
factors of the BELIEF trial. As in the real world, there will never be a silver bullet to solve every single
problem.
The key point is to assess all available options on the table and do a weightage between the risks and benefits to
come up with a decision for the greater good for the patients, stakeholders and industry.
3.1 SUITABILITY (WOULD IT WORK?)
The BELIEF trial would not have existed but because of the promising results from the previous animal testing.
Huges, et al. (2002) reported prior to the year 2002, six prospective randomized animal TMR controlled trials
have demonstrated the efficacy of surgical TMR for decreasing anginal symptoms in patients ineligible for
traditional methods of revascularization.
In term of suitability, the many extensive data collected from animal testing, bench testing and in vitro studies
have identified the suitability to be practiced on a human subject. The hard question is to identify, qualifies and
characterize the actual mechanisms of action which is still an never ending work in progress.
3.2 FEASIBILITY (CAN IT BE MADE TO WORK?)
There will be many unforeseen circumstances that lead to more questions than answer. Therefore, there will
always be trial and errors while conducting any clinical trial, the author believes that the utmost important task
is to prevent and reduce injury and harm to the participating patients.
By designing a robust clinical trial with the mind and concern of patient’s safety first is definitely the right
approach. Stone, et al. (2015) reported the primary and secondary endpoints should be selected such that

meeting these endpoints will demonstrate reasonable assurance of safety and effectiveness and a favorable
benefit-risk profile.
The design of any clinical trial should, therefore, be focusing first on the feasibility of going through the safest
ways (no short-cut) to achieve the primary and secondary endpoints objectives.
3.3 ACCEPTABILITY (WILL THEY WORK IT?)
The author believes there will be consensus effort among the various stakeholders to work on and fine-tune any
similar BELIEF trial in the future because until now, the no options patients are still without any real options.
Leon, et al. (2005) reported the patients studied in these similar BELIEF trials had severe angina symptoms who
had exhausted all forms of conventional therapy.
They were highly motivated and desperate for a novel therapy to provide symptom relief, and they had high
expectations for clinical benefit. Therefore the author strongly advocate more research to be carry out in the
field of Percutaneous Myocardial Laser Therapy to discover more finding and revealing the side-effects so as to
allow more research fellow, professional medical personnel and suffering patients to see the pro and con before
accepting the Percutaneous Myocardial Laser Therapy as a suitable, feasible and acceptable long-term
treatment.
End of Report

REFERENCES
Bridges, C.R., Horvath, K.A., Chiu, R.C. & Wiley InterScience (Online service) (2006) Myocardial laser
revascularization. Blackwell Futura, Malden, Mass.
Bonetti, P.O., Holmes, D.R., Lerman, A. & Barsness, G.W. (2003) Enhanced external counterpulsation for
ischemic heart disease: Placebo effect of myocardial laser revascularization is important. Journal of the
American College of Cardiology, vol. 41, no. 11, pp. 1918-1925.
Becker, K.M. & Whyte, J.J. (2006) Clinical evaluation of medical devices: principles and case studies, 2nd edn,
Humana Press, Totowa, N.J.
Cooper, C., O'Cathain, A., Hind, D., Adamson, J., Lawton, J. & Baird, W. (2014) Conducting qualitative
research within Clinical Trials Units: avoiding potential pitfalls. Contemporary clinical trials, vol. 38, no. 2, pp.
338-343.
Granger, C.B. & Gersh, B.J. (2015) Potential relief for refractory angina. The New England journal of medicine,
vol. 372, no. 6, pp. 566-567.
Galiñanes, M., Loubani, M., Sensky, P.R., Hassouna, A., Cherryman, G.R., Leverment, J.N. & Samani, N.J.
(2004) Efficacy of transmyocardial laser revascularization and thoracic sympathectomy for the treatment of
refractory angina. The Annals of Thoracic Surgery, vol. 78, no. 1, pp. 122-128.
Howick, J. (2008) Double-Blinding: The Benefits and Risks of Being in the Dark. In Fennell, D. (editors).
Centre for the Philosophy of Natural; and Social Science Contingency and Dissent in Science Technical Report.
(03/08). London, The London School of Economics and Political Science.
Haynes, B. & Haines, A. (1998) Getting research findings into practice: Barriers and bridges to evidence based
clincial practice. British Medical Journal, vol. 317, no. 7153, pp. 273.
Hughes, G.C., Biswas, S.S., Yin, B., Baklanov, D.V., Annex, B.H., Coleman, R.E., DeGrado, T.R., Landolfo,
K.P., Landolfo, C.K. & Lowe, J.E. (2002) A comparison of mechanical and laser transmyocardial
revascularization for induction of angiogenesis and arteriogenesis in chronically ischemic myocardium. Journal
of the American College of Cardiology, vol. 39, no. 7, pp. 1220-1228.
Kramer, D.B. & Cutlip, D.E. (2015) Trust and transparency in clinical trials of medical devices. Nature Reviews
Cardiology, vol. 12, no. 9, pp. 503.
Leon, M.B., Kornowski, R., Downey, W.E., Weisz, G., Baim, D.S., Bonow, R.O., Hendel, R.C., Cohen, D.J.,
Gervino, E., Laham, R., Lembo, N.J., Moses, J.W. & Kuntz, R.E. (2005) A Blinded, Randomized, Placebo-
Controlled Trial of Percutaneous Laser Myocardial Revascularization to Improve Angina Symptoms in Patients
With Severe Coronary Disease. Journal of the American College of Cardiology, vol. 46, no. 10, pp. 1812-1819.
Michael, H. Crawford. (1999) TMR Revisited. Clinical Cardiology Alert, vol. 18, no. 11, pp. 81.
Nordrehaug, J.E. & Fauls, J.M. (1999) BELIEF: A randomized, Sham-procedure-controlled trial of
Percutaneous Myocardial laser therapy. In Becker, K.M. & Whyte, J.J. (editors). Clinical evaluation of medical
devices : principles and case studies. (2nd edition) (2006). Totowa, NJ: Humana Press Inc.

Robinson, M. & Cook, S. (2006) Clinical trials risk management. CRC/Taylor & Francis, Boca Raton.
Roy, J. (2012) Randomized treatment-belief trials. Contemporary Clinical Trials. 33. pp.172-177.
Redberg, R.F. & Dhruva, S.S. (2012) Evaluating Sex Differences in Medical Device Clinical Trials: Time for
Action. JAMA, vol. 307, no. 11, pp. 1145-1146.
Science Letter editors. (2008) Clinical Trial Participation Unaffected by Disclosure of Investigator's Financial
Stake. Food and Drug Law Journal Article Finds 2008, , NewsRX LLC, pp. 292.
Stone, G.W., Vahanian, A.S., Adams, D.H., Abraham, W.T., Borer, J.S., Bax, J.J., Schofer, J., Cutlip, D.E.,
Krucoff, M.W., Blackstone, E.H., Généreux, P., Mack, M.J., Siegel, R.J., Grayburn, P.A., Enriquez-Sarano, M.,
Lancellotti, P., Filippatos, G., Kappetein, A.P. & Mitral Valve Academic Research Consortium (MVARC)
(2015) Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and
Replacement: Part 1: Clinical Trial Design Principles: A Consensus Document From the Mitral Valve Academic
Research Consortium, Journal of the American College of Cardiology, vol. 66, no. 3, pp. 278.
Saririan, M. & Eisenberg, M.J. (2003) Myocardial laser revascularization for the treatment of end-stage
coronary artery disease, Journal of the American College of Cardiology, vol. 41, no. 2, pp. 173-183.
The EU Clinical Trials Register (No date) About the EU Clinical Trials Register. Available at:
https://www.clinicaltrialsregister.eu/about.html (Accessed: 21 Feb 2016).
ClinicalTrials.gov (2015) Background of ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/about-
site/background (Accessed: 21 Feb 2016).
<End of References>

Academic Report On The Pitfalls Of Clinical Trial For Medical Devices

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