Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 40
5. Improving the Translation of Research Findings
into Clinical Practice: Some Opportunities for
Change
The increase in knowledge concerning human health and the mechanisms of disease
has been so rapid during the second half of this century that the present era has
been described as that of the biological revolution. This biological revolution may
prove as decisive for the future of medicine as the industrial revolution was for
economic development in the past (77~. The extent to which this occurs, however,
depends in part on the effectiveness and efficiency of the process by which advances
in biomedical research are translated into clinical practice. As indicated earlier, in
medicine this translation or the development process includes three components: the
development of new drugs, of medical dewces, and of clinical procedures.
This paper has described the similarities and differences that exist among the
development processes for drugs, medical devices and clinical procedures. A primary
difference concerns the asymmetry of the evaluative strategies employed: drugs have
over the last quarter century come to undergo rigorous clinical testing before their
introduction into general use, while clinical procedures are still being assessed only in
a more ad hoc fashion, and new medical device evaluations are to be found
somewhere in between. It might be expected that this asymmetry reflects important
differences in the effectiveness and efficiency of the three different processes by
which research findings are translated into clinical practice. Following are some
major observations with regard to these differences, and some inferences as to
opportunities for improvement.
He Develop~,tent of Drugs In comparison to the medical device industry, the
multinational pharmaceutical industry is older, highly regulated and very research-
intensive. The pharmaceutical industry annually invests approximately $6.5 billion in
R&D in the U.S. (about 17 percent of sales52), roughly $1.5 billion of which goes to
pre-marketing clinical testing. The investments in research, but especially those in
development, are consistently increasing (since 1980, an increase of roughly 30%~.
According to the Wiggins analysis, the R&D process is estimated to now cost $125
million per marketed new chemical entity (NCE)~151~.
On the input side, the resource commitments to drug R&D, the relevant scientific
knowledge and the technical capabilities have al] grown impressively since the 1950s,
52 The OECD in general defines industrial companies with If% of their turnover
in R&D already as "research intensive."
40
OCR for page 41
but this growth has not been reflected on the output side, at least not quantitatively
(85). The number of NCEs entering human testing fell from a mean of 89 a year in
the period 1950-1962, to 35 a year in 1963-1972, to 17 a year in the period 1975-
1979 (an overall reduction of 81 percent) (95,97,76). In recent years, IND filings in
the U.S. are increasing again especially those for biological drugsS3 (116). But these
INDs are increasingly acquired from non-U.S. sources. Especially noteworthy is the
fact that Japan has been increasing as a source since the early 1970s, by the end of
the 1970s surpassing Europe, traditionally a stronghold for producing new chemical
compounds (see Figure 3). A similar trend occurs with regard to the number of new
drug approvalsS4.
Figure 3: Origin of NCEs on which INDs have been filed by US-owned firms.
tar
14t
13
12
~ ~0
U
At
o
MU
3
it
6 _
4 _
2
1
o
Source: (95)
-
~ , ~
ye
\
~ ~ JAPAN
, ^% /
Jan ,^ EUROPE
-. ... , /e ,*- -U.S.
~ ~-"'1"-.''''",,,
-
lt64 lg64 1968 1970 1972 1974 1976 1978 19" 1982
YEAR OF IND flLING
53 One furthermore should keep in mind that, whereas the success rates of
NCEs are higher for 1970 cohorts than for earlier cohorts, at present 73 percent of
NCEs initiating human testing are still discontinued before an NDA is submitted
(135~.
54 The number of drugs approved for the U.S. market averaged 36 NCEs per
year between 1950 and 1960. A decline of 54 percent occurred in the early 1960s,
after which the numbers fluctuated, averaging 14 NCEs per year, through the end of
the 1970s. Since the end of the 1970s, approval rates recovered somewhat (26 in
1985, 20 in 1986), though this recovery did not specifically take place in US-
originated but in foreign-owned approvals (95,97,76~.
41
OCR for page 42
Over the years these output measures of the development process have been
extensively reviewed in the literature and the halls of Congress (see Appendix I).
The dates given above indicate that the beginning of the decline in the number of
new U.S. drug introductions occurred at roughly the same time as the introduction of
the 1962 amendments to the Food, Drug and Cosmetic Act. A substantial body of
policy analysis was undertaken to consider the causal effect of these regulatory
changes on the declining number of new drug approvals. Originally it was concluded
that the decline in drug introductions could be attributed fully to changes in
regulatory requirements for evaluative practice during development. Currently,
however, in view of the increasing recognition of social, economic, managerial and
political factors as determinants of the decline, it is apparent that no such
straightforward link can be established (133~. Nonetheless regulatory requirements --
and their interpretation by the regulatory agencies concerned -- remain an important
factor in the potential rise and fall of new drugs; not to mention the scientific,
commercial and public perceptions of such regulations as determinants of whether
and how a drug is developed.
Generally speaking, these regulatory configurations and the resulting clinical
P.~l~tinnc have lerl to important henPfit~Ss TInt1er ~or.i~1 and political pressures,
time. As a result the
t~me-span ot pre-mar~et~ng development has Increased trom about 4.5 years in 1964
to 9 years in 1984 (95). This interval has reached a point where access to useful
new drugs may be delayed. The tension between increasingly thorough pre-
marketing evaluations and early availability becomes urgent in the case of life-
threatening disease.
^~ ~ 4~~ ~~ berm ~ . --em . ~~ . he ^
these requirements have become increasingly detailed over
.. ~ ~ .. . . . ~ . . ~
For example, the prominence of AIDS has raised two fundamental issues as to the
clinical basis on which decisions are being made. The first concerns the endpoint
issue mentioned earlier, i.e. considerable uncertainty exists as to what endpoints
should be evaluated during which stage of the development process. For instance, to
expand on the AIDS example, the questions concerns whether and in which cases
intermediate endpoints (instead of survival) should be evaluated in pre-marketing
trials. Equally, the question concerns whether and when quality of life endpoints
should be built into the developmental evaluation process.
sS Notably the structural prevention of potentially unsafe and/or ineffective drugs;
these basic premises on which the regulatory system is based are generally considered
valuable. However, it is interesting that -- in contrast to the medical device
amendments -- there is no legal mandate to encourage development and innovation,
but only to assure the marketing of "safe and effective" drugs (85~.
42
OCR for page 43
The second issue concerns the balance between pre- and post-marketing evaluation,
regarding which some new initiatives have recently materialized. The FDA, for
example, has proposed to streamline the drug approval process for life-threatening
diseases by shortening the pre-marketing evaluation stage (Phase IT and Phase ITI
clinical trials wall be merged into more definitive Phase IT trials), and by emphasizing
more strongly the post-marketing evaluation stage (Phase {V) for providing safety
and effectiveness information on a new drug. Even apart from life-threatening
diseases, there is a general need for such Phase IV information, because the full
range of a drug's risks and benefits wall emerge only when it is used in actual
circumstances of clinical practice. Drugs, once marketed, are subject to empirical
innovation -- just like devices or clinical procedures. That is, in the hands of
physicians trying to solve problems, new theories are spun out and drugs are used as
if those theories were true (e.g., cimetidine). It is only through Phase IV monitoring
and surveillance broadly construed (i.e., regarding general use) that the identification
of these theories can be accelerated and steps taken to assure their timely testing.
AS argued in Chapter 2, the Phase {V studies that would provide this information
wait depend heavily on observational methods. In recent years, methodological
advances (see below) have opened up new opportunities for inexpensively monitoring
the use and long-term risks of drugs. These methods may well be useful, not only in
providing risk information, but also in providing effectiveness information. So far,
however, uncertain prevails as to the scientific value of the practical application of
these methods to medicine in general and drugs in particular. In view of the
potential effects of these methods on shifts between "development" phases and the
subsequent implications for medical innovation in general, any serious investment
strategy for medical technology development must address the possible promise of
such an application.
A broader argument exists to carefully consider the potential and problems of post-
marketing evaluationS6. The increasing time-span of development has not only made
the process more costly but also has decreased the return on investments by lowering
the effective patent life of new pharmaceuticals. The average patent life of NCEs,
from date of approval to expiration of the patent, was 16.3 years in 1960 and roughly
9 years in the mid 1980s57. The need to consider patent life was recognized in the
U.S. and the "Drug Price Competition and Patent Term Restoration Act" was
s6 For example, getting a drug on the market one year earlier would reduce the
average break-even point economically (i.e. R&D costs equal revenues) by 3 to 4
years (61~.
s7 Grabowski (61) has analyzed that it would take 12 years of projected revenues
at the present rate to achieve a read return on capital of ~ percent. A 10 percent
real return would require 19 years of projected revenues at the present rate.
43
OCR for page 44
enacted in 1984. The law however restores only some of the patent life lost during
the regulatory process as it also allows generic drugs to receive more speedy
marketing approval through a system of abbreviated NDAs (ANDAs)58. The overall
result of this law is that the effective exclusive marketing time of innovative products
has not increased because generic drugs can be marketed more rapidly. The impact
of this law may be considerable since Sl of the most important 100 drugs used
currently in the U.S. will go off patent by 1991 (and will thus become generic
drugs)5 . Furthermore the economic climate is becoming much more price
competitive e.g. most states have passer] pro-generic substitution laws (allowing
pharmacists to dispense generic drugs for the brands specified on the prescription
forms)60. Whereas industries other than the pharmaceutical such as electronics or
optics but also the medical device industry can react to more competitive
environments by decreasing the turn-arounc] time of their innovative cycles such a
strategy will be much more difficult in a pharmaceutical industry subject to long and
relatively fixed R&D cycles.
Although the pharmaceutical industry has generally been very profitable and recent
advances in biomedical research seem to present exciting opportunities for the
development of new drugs the trends visualized in Figure 4 may constitute an
impediment to drug development in the long run. Whereas the effective translation
of research findings into clinical practice will require information on the health
outcomes of a drug in general use the above underlines the necessity to provide this
information as efficiently as possible.
58 Furthermore while the advantages for generic drugs can be reaped
immediately the advantages inherent in the law for innovative products can only be
reaped further in the future (i.e. at the point where the patent term would have
expired without the law).
s9 Although a drug may continue to earn positive profits after the patent
expiration date under the pressure of generic competition sales of a patent-expired
product currently fall by SO percent or more in the 2 or 3 years after patent expiry.
60 Furthermore hospital formularies favor the lowest cost products and the
Maximum Allowable Cost Program reimburses Medicare patients only for the
lowest cost product. In addition international competition from Japan and Europe
has increased (recently the EEC introduced the protection of the exclusive rights of
the company that submits a file for regulatory approval. Files of new products
irrespective of the patent situation watt remain inaccessible to others for up to 10
years from the time the first EEC approval has been granted (148~.
44
OCR for page 45
Figure 4:
1 Bus - ~~
As costs nse . patents are eroded
.
R & D expenditure by US companies Effective patent life of new
in America sea ages ~'p~ 4 s ~ drugs in America Yws ,6
. ~ .. .....................................................................
........................ ..... ...... ... ;/ 4 0 ~ ~ 14
~ . ~`j;
. ;~;~ ~ 12
.......................... 7~ 3 ~.0. ~ . ~
_ 2 5 . ~;
. ;,~ ~ ~ . ~
.~ 2 0. .................................................... ~.8.
........................................................... 1.5 ... 6
ED F - a ~ ..................................................................
- . , ~ _~ , _ , _ ~ _ , ~
1981 83 85 87 89 1962 66 70 74 78 82 84
;..and competition increases ~
.' ~
.
Number of drugs under
development worldwide 200
.....................................................................
1980~100 ~
~ 180
. j,
1 160
. ~
/ 140
.................. ............................
~ 120
':.........................................
, _ ~ ~ _.'.00.
1981 82 83 84 85 86
.................. N
~ )
........................... 0
Source: Economist, February 1989
The Developmentof Medical Devices Moving from the pharmaceutical to the medical
device industry, the latter is younger, more nationally oriented, and characterized by
smaller firms; the image of the innovative engineer developing a device prototype in
his basement, garage, or study still has some relevance, although it may become a
metaphor in the 199Os. In recent years the market for medical devices has been
growing rapidly. The overall U.S. medical device market is estimated at over $20
billion dollars in 1987, and parts of that market are expanding at annual rates
ranging from 10 to 25 percent (135~. Investment in medical devices R&D is smaller
than for pharmaceuticals. On average, medical device firms invested 7.5% of sales in
R&D in 1988 (~17), and it appears that this percentage remains relatively stable.
Differences in R&D investment can be observed to depend on the size of the firm,
and the particular type of device under development. For example, small firms
invest almost double the industry average (~19~.
In comparison with drugs and biologicals, there is a much greater heterogeneity in
medical devices in terms of design, purpose, and use; and
variation in the kind of clinical evaluations undertaken (129~. In view of this
heterogeneity, the medical device amendments to the FD&C Act divided devices into
three classes and differentiate the level of regulatory control according to the
likelihood of risks inherent in a particular device class. Whereas, ninety percent of
all new medical devices are subject to "genera] controls" (including good
manufacturing practices, pre-marketing notification and, potentially, technical
performance standards), only 10 percent of new medical devices are subject to full
pre-marketing review for safety and efficacy (55~. It is interesting to observe that
(unlike the Drug Act) the device amendments explicitly incorporate in their mandate
the need to encourage medical device developmental.
consequently much more
6] "It is the purpose to encourage, to the extent consistent with the protection of
4s
OCR for page 46
In contrast to pharmaceutical innovation, there is a steady growth in the number of
medical devices entering clinical investigation (17~. In the past few years, IDEs62
include an increasingly broad range of investigational devices. But, since 1980, the
proportion of TDE `devices that in first instance successfully completed their
developmental evaluation has decreased to 30 percent (although eventually 80
percent are approved). This decrease reflects the more complicated safety and
efficacy issues surrounding new investigational devices, a more stringent regulatory
climate, and the relative inexperience of many device manufacturers (80 percent of
the device developers have only submitted one IDE since 1980~. In terms of
efficiency and effectiveness of development, those who submitted 7 or more IDEs
since 1980 had an approval rate twice as high as those who submitted only one IDE
(17~. The impression exists that the R&D cycle of incremental device innovations is
only 2 to 3 years, whereas with radical device innovations (such as ultrasound or
MRI) it is more like 10 years. Development times then can be estimated to range
roughly from ~ year for incremental devices to 5 years for radical devices.
Unlike drugs, a medical `device is generally not created "de nova" but arises in a
development process typically representing continuous technical modification and
incremental improvement. Clinicians provide significant input by evaluating the
clinical efficacy and safety of a device as well as by suggesting technical
improvements to enhance its clinical utility. For certain devices the users are also
the innovators, designing and building the original prototype (68~. Although already
fairly common, close interaction between device manufacturers and the clinical
community is an even more crucial prerequisite for effective and efficient device
innovation than is the case with pharmaceutical innovation.
. , ,
The initial evaluation stage of a new device usually depends on careful clinical
observations based on informal experimental methods. The main question at this
stage concerns whether the device prototype has the postulated effect in humans and
may be clinically useful. As indicated above, this pilot stage then normally leads to
improvements in a device's design and materials. Chalmers (26) has argued for
randomizing the first patient who receives a procedure involving a new medical
device (or a new surgical technique). In view of the technically evolving nature of
the device and the fact that investigators usually must be educated and trained in
the public health and safety and with ethical standards, the discovery and
development of useful devices intended for human use and to that end to maintain
optimum freedom for scientific investigators in their pursuit of that purpose" (520,
Aim
62 TDEs are devices under development which require FDA approval to initiate
clinical evaluation in humans.
46
OCR for page 47
how to operate certain equipment, randomization of the first patient is generally not
considered feasible (this equally holds for surgical techniques). This then does raise
the question of the timing of (a multicenter stage of) safety and efficacy evaluations,
when exactly in the development process should these evaluations be initiated. If
these studies are undertaken too early, the changing characteristics of the device may
render the results obsolete. If they are undertaken too late, the results may be
unimportant for decision making. Ideally, these studies would be based on
randomized controlled trials. However, in many cases, the RCr as generally used in
drug studies (involving double blinding and placebo controls) mI] be much- more
difficult to undertake, especially with diagnostic devices. In such cases other well-
controlled study designs wall have to be used to evaluate efficacy. Until recently,
however, new device evaluations often are uncontrolled (129), and the use of
adequate controls needs to be stimulated. Once the device has been approved and
diffuses into more general practice, its long-term safety and effectiveness should
remain parameters of the dev~ces's 'long-term' development evaluation. Because
device development often involves incremental innovation (for a considerable part of
its lifespan) and because RCrs are not ideally suited to provide information on a
slightly different version of a device, these studies wild usually depend on
observational methods.
When comparing the effectiveness and efficiency of device development to drug
development and considering the welI-known methodological weaknesses of
traditional observational methods, it is timely to assess the strengths and weaknesses
of new non-experimental methods for providing reliable information about the health
effects of new medical devices. In the quest for improved and more reliable
methods of clinical device evaluation, however, it is necessary to consider the
importance of small device firms in medical device innovation. One will need to
keep in mind the potentially differential impact such requirements could have on
small versus large firms, in terms of viability, innovation potential, competitiveness,
etc.
As discussed in Chanter 4. the distinction
The Development of Clinical Procedures
between "developers" and "evaluators/users" is a thin line in the development of
clinical procedures. In- comparison to drugs and devices, no governmental regulatory
system governs their development. The evaluation of developing clinical procedures
is based in principle on the trust relationship between physicians and patients.
Initiation of development and its evaluation thus depends heavily on professional self-
regulation. In this respect the difference between radical and incremental
innovations is important. Radical innovations may frequently originate in academia-
or academic-associated centers, and are generally subject to approval by Institutional
Review Boards (IRBs). A larger part of developmental efforts, however, concern
incremental improvements in existing procedures. In cases of incremental
improvement, the line between experiment and individualized therapy generally is
47
OCR for page 48
difficult to draw clearly, with the result that TRBs are not usually approached for
approval.
There is very little information available on investments in R&D for clinical
procedures. It appears, however, that considerable changes may be taking place as
to the source of funding in this area. For example, wheras traditionally the
development of many procedures was cross-subsidized through patient care revenues,
with the changes in hospital reimbursement these funds are decreasing. Very little
information is also available on the aggregate number of new procedures being
developed as we]] as an the average time needed for deveic~nment.
During the development process new clinical procedures generally have not been
systematically evaluated in terms of safety, efficacy and effectiveness. Traditionally,
their evaluation during the development process often depended on non-formal
evidence or the use of historical controls; this usually leads to more optimistic results
as to the potential benefits of a new procedure than would have been the case from
well-controlled studies (574. As a result, the scientific evidence normally assumed to
support day-to-day clinical practice is not always provided in a systematic and timely
fashion. For example, a number of procedures were discarded only following their
widespread use, when they were found to be ineffective on the basis of well-
controlled studies. For some of these procedures, the weak quality of their clinical
evidence is illustrated by considerable geographic variations in their use, such as
those for coronary artery surgery, hip replacements, or lower back surgery. To
achieve an effective development process for procedures, more systematic and
improved evaluative strategies are needed.
Such an improvement wait need to take into account that the development of clinical
procedures is a very different endeavor from that of drugs and devices. The
development of especially incremental innovations often occurs in a decentralized
manner, involving change and refinement of a particular procedure by numerous
physicians. During the initial development of a new procedure, the skills and
experience with a technique still evolve and the risk/benefit ratio may change
considerably. Pilot or feasibility studies at this stage will have to include "systematic
and comprehensive collection of clinical experience" to determine whether a
procedure works and to differentiate patients according to prognostic factors (22~.
However, many clinical procedures do not now receive the careful Phase ~ studies
required for drugs (144~. If and when the feasibility of a new procedure has been
established, randomized clinical trials or otherwise welI-controlled studies should be
undertaken at selected institutions. The transition from the feasibility study by a few
developers to multi-center investigation is more difficult to determine with clinical
procedures than is the case with drugs and even devices. Systematic surveillance of
early clinical evidence could facilitate the timely implementation of such well-
controlled studies. After efficacy has been determined under such trials, evaluation
en en ~
Ha · _ _ e ~ ~ . a a ~ a ~ Ha
48
OCR for page 49
of a procedure's effectiveness and safety should again remain parameters of
clevelopment evaluation.
Compar~rlg the Outcomes of Drugs, Devices and Clinical Procedures Ultimately clinicians
and patients, of course, are concerned with choices among a spectrum of alternative
diagnostic and treatment technologies and want to Mow, for a clinical condition,
which treatment is best for which patient. The rational assessment of technology
thus requires a holistic and balanced strategy for assessment that provides
comparable information about its relevant outcomes for all relevant technological
options. This paper has already noted the present imbalance in regulatory
assessment strategies that provide extensive documentation of (at least some)
outcomes for drugs compared to other drugs or to placebos, while little attention is
given to understand the relative merits of drugs compared to devices or to clinical
procedures. The treatment of angina, gallstones or prostatism are examples where
all three types of technology have been developed. but have as vet not received
comprehensive and ongoing evaluation.
~ ,
This paper does not intend to imply the need for a federal regulatory system
governing the development of procedures. Alternatives to such a system have been
proposed. Bunker et al have suggested the establishment of a central reviewing
authority (under which the various TRBs could resort) to initiate and coordinate
clinical procedure trials as appropriate (22~. The initiation and coordination of
studies determining effectiveness and (Iong-term) safety of a procedure would also be
part of such an authority's mandate.
The Bunker mode] does not, however, call for the systematic comparison of
technological options (including drugs and devices). A more recent mode] may be
found in the assessment teams now being initiated by the National Center for Health
Services Research to evaluate alternative technological options available in the
management of clinical conditions. These teams are to undertake the equivalent of
Phase ~ and Early Phase IT studies now undertaken for `drugs, make
recommendations for clinical trials (Phase IlI), and conduct Phase IV studies for new
as well as established clinical procedures. These teams wall focus on specific clinical
conditions, such as benign hyperplasia of the prostate and stable angina. They wall
assess all relevant treatments and thus provide information on the relative safety and
effectiveness of drugs, devices and procedure. Drug and device manufacturers could
be expected to have interest in helping to fund these teams. Whereas -- on the
positive side -- this scenario would imply that the stronger financial sectors of our
health care system would share the financial] burden of performing evaluations of
clinical procedures, their involvement could result in possible conflicts of interest.
This policy question will need to be addressed if the assessment team approach is to
prove a realistic mechanism for the systematic evaluation of alternative medical
technologies.
49
OCR for page 50
~ -
· e ,
In conclusion, serious inconsistencies exist in the evaluation of drugs, devices and
procedures during their development process. The above indicates that these
Inconsistencies may have contributed to shortcomings in the effectiveness and
efficiency by which biomedical research findings and clinical theories are translated
into clinical science and useful clinical practice (see' Table 11.
.
Furthermore, these
inconsistencies may also have contributed to unnecessary health care costs, if one
takes into account that the least svstematical~v evaluated technologies. clinical
~ .' ~ ,
procedures, are also the most costly63. Although these inconsistencies are to a
certain extent a result of inherent differences among the development processes of
drugs, devices and procedures, these differences do not seem to preclude a more
balanced approach to assessing an medical technologies. Such an approach would
strengthen the clinical evidence on which development decisions are made, and
probably would improve the cost-effective use of health care resources.
Table I: Comparison of Effectiveness/Efficiency of Technology Development
l
Drugs Devices Clinical |
Procedures
· R&D Investment +++ + ?
· Development Time ++ + ?
· Number of New
Innovations entering
Health Care + ++ ?
· Clinical Basis for
Decision Making:
- Pre diffusion +++ i ' +
l - Post diffusion + +
63 Consider' eager the management of angina. The development of coronary
artery bypass surgery and that of beta-blockers were initiated roughly the same time.
The imbalance in assessment strategies, however, implies that the surgical option
could undergo much more rapid diffusion than the pharmacological option, as beta-
blockers were not as rapidly available to practicing physicians.
50
OCR for page 51
The paper concludes that. to achieve a proper balance Three issues can be identified
that might fruitfully be addressed. by the workshop. Theorist issue concerns the
criteria or endpoints of development evaluation. With regard to determining a
technology's safety and efficacy, the role of intermediate endpoints in comparison to
mortality, functiona.] status or quality-of-life endpoints should be clarified. In addition
to clinical and scientific.considerations, the endpoint issue raises economic concerns;
i.e. these decisions may have large. consequences for the length and-costs of pre-.
marketing development. Both these. consid.erations.would need to be taken into
account. Furthermore, following the approval decision for new drugs and devices
and the more widespread diffusion of-new procedures, it. wall be increasingly
important to include health.. outcomes in "real world" clinical practice as important
evaluative endpoints (n.b. for.diagnostic.technologies this. may be inappropriate3. In
view of the increasing numbers of alternative or competing technologies being
developed, it seems especially important to provide comparative evaluations of the
relative safety and effectiveness of technological options available in the management
of clinical conditions. Inherent in these evaluations would be the need to incorporate
patient preferences for the health benefits and risks associated with alternative
technological interventions.
The second issue concerns the methods for providing such information. Evaluation
of the risks and benefits of new technologies during their development wild have to
rely not only on experimental methods (including, randomized controlled clinical
trials), but also on improved observational methods of clinical evaluation. This
applies for devices and especially clinical procedures, but also to drugs; for example,
these kind of studies can provide needed information on the long-term health
outcomes of drugs in everyday use.
In comparison to RCTs, these observational methods are usually considered to be
the weaker methods of clinical evaluation. However, recent methodological advances
may have addressed some of these weaknesses. It has been observed that (144~:
3.
4.
Advances in statistical methods, for instance those in Bayesian
statistics, make it possible to assess outcomes for alternative
treatment strategies. These methods are useful for assessing
outcomes in non-experimental study designs.
The increased availability of large-scale automated data systems
and improved methods of data base linkage, make it possible to
inexpensively monitor use and outcomes.
Advances have occurred in measuring the effects of a new
technology on functional status and the quality of life of patients.
Advances in decision analysis provide means to assess the
importance of patient preferences and of the uncertainties about
the probability for specific health outcomes.
51
OCR for page 52
In view of these advances, it seems especially timely to explore the strengths and
weaknesses of modern evaluative methods within the under context of existing
methodologies.
Third, depending on their strengths and weaknesses, a policy and institutional
framework will have to be established for assuring the application of non-
experimental methods as appropriate. For example, the workshop might consider
alternative models for assuring the systematic evaluation of clinical procedures.
It is only by addressing these complicated issues that will we be able to improve the
effective and efficient transfer of research findings into clinical practice, and thereby
strengthen a crucial link in the medical innovation chain.
52
Representative terms from entire chapter:
medical device
