HUM-MOLGEN archive: DIAG,ETHI: re:"Widening gap..." 12 submessages

************************************************************** HUM-MOLGEN DIAGnostics/Clinical Research ************************************************************** This DIAG message contains 12 submessage(s): 1) 10 replies re: "Widening gap between clinicians and scientists" 2) Editor's comment 3) Copy of the original message Carlo Gambacorti MD, Editor, Human Molecular Genetics network Diagnostics/Clinical Research Section ************************************************************** ************************************************************** I agree with most of the observations raised. As an MD/PhD spending more time in the lab than the clinic, I have seen and heard both sides of the story, in N America where I did my PhD and postdoc, and back home now in Singapore, where the MD/PhD is still a rare (but growing) species. The S'pore system is modelled on the UK one, where clinicians doing research generally do so on their own time. Despite a continuing interest in clinical practice, I sought employment in a research capacity so as to ensure "protected time" in the lab. Thanks to a growing appreciation of the need to bridge the 2 worlds of bench research and clinical medicine, I have been allowed to retain clinical privileges.This arrangement is possible only through the generosity of my fulltime clinician colleagues on the team who provide cover during those times that I am unable to attend my clinical responsibilities because of research commitments. I must emphasise, however, that mine is the exception rather than the rule. In addition, the decision to spend more time in the lab meant a significant salary decrease. Since people in the clinical and research worlds each speak a different jargon, it is not surprsing that there is often no communication, miscommunication, and even hostility, between the two groups. My training in both fields has allowed me to bridge this chasm to some extent, and it is encouraging to be able to introduce friends from one world to the other occasionally, and to find that with a little effort on each side, they can begin to understand each other and even to co-operate and collaborate. It would be unrealistic to recommend that everyone train as an MD/PhD but I believe it would be useful for clinicians be exposed to some research training during their training, and biomedical scientists be given some understanding of the practical problems that exist in the clinical realm. From: Agnes Tay <mcbtayhn@LEONIS.NUS.SG> ************************************************************** I just thought that you might like to have the perspective of a parent with a 2-year-old girl who has either Infantile Adrenoleukodystrophy or Infantile Refsum's. I am also doing a Ph.D. thesis in the area of organizational psychology. I think that it is wise for scientists and clinicians to work together to improve the lag time between laboratory experiments and clinical trials. The general public has easier access to clinical information than ever before. It seems to me that clinical medicine is not keeping up with the information age. I found a researcher in another country who happens to also be a clinician to treat my daughter; something my daughter's pediatrician wouldn't have done. As a result, my daughter is no longer completely blind (she sees well enough to track her toys), her motor development has improved, as has her cognitive functioning. Her prognosis may or may not be the same, but her quality of life, and thus her parents' quality of life has improved. This is also likely the most cost-effective treatment as well since her physical health is also better; she has not had any hospitalizations, and no doctors visits other than for immunization. Having said this, I still have a daughter who is two and doesn't walk and doesn't talk. I keep hoping that a gene therapy trial will be available to my daughter while she is still a young child. I hate to think that poorly organized information transfer could mean the difference between a child having a life and not having a life. Kathy Momtahan kmomtaha@CCS.CARLETON.CA ************************************************************** This is a response to the "widening gap between clinicians and scientists" message we just received. I am a genetic counsellor in clinical practice. I am not funded by research, but I have extensive contact and involvement in research projects around the world which are of interest to my patients. This is especially important for patients with rare disorders, for whom molecular studies are not routinely available through clinical service laboratories. For instance, if I see a patient with a rare disorder, I might try to locate a research group (from recent publications or meetings) that has done or is doing work on that disorder, and offer the participation of the family in the studies. These patients and families are often highly motivated to participate in research studies, sometimes (at least in part) for altruistic reasons, which is of great benefit to the scientists engaged in such research. At the same time, however, these families often have other, very personal reasons for participating in the research, since it may provide information of great clinical relevance to them - for example the potential for prenatal diagnosis in future pregnancies. This is where the relationship between the research laboratory and the clinicians is critical - the clinicians provide samples and clinical information on the patients and families; the researchers provide molecular or other results which can then be shared with families. But, unlike clinical practice, the focus of a research laboratory is not on the individual family. Some of the issues which need to be addressed in the relationship between clinical service and basic (clinical) research are quality control, length of time for results of testing, accuracy and interpretation of data (eg linkage data), and (let's be honest about this) authorship in the case of publications. I'd be interested in hearing from other genetic counsellors who provide similar service to their patients, and from the research groups who are on the receiving end. _______ Marlene Huggins, MSc huggins@sickkids.on.ca Genetic Counsellor ph: (416)813-5338 The Hospital for Sick Children fax: (416)813-5345 555 University Avenue Toronto, Ontario Canada M5G 1X8 ************************************************************** >Questions that interested readers could try to answer are: > >1. do you agree in general with this analysis ? >2. do you think this trend represents an inevitable > development ? >3. do you have comments, ideas or proposals ? > I agree with most of this analysis. Do you find Clinician/scientists have better chance to be in (higher) positions leading (directing) clinicians and scientists? Chen-Jee Hong, M.D. Investigator Molecular Genetic Lab Department of Psychiatry Veterans General Hospital-Taipei Shi-pai Road, TAipei, Taiwan Fax: (H)02-8742441, (O)02-8757592 Phone: (O) 02-8757027 ext. 267, 268 Phone: (H)886-2-8752616, (O)886-2-8757027 ext.267 e-mail: cjhong@vghtpe.gov.tw ************************************************************** In general I agree with your assessment and believe that some of this is a result of which professional activities are valued and endorsed by our (US) academic institutions. However as public funds become even more difficult to obtain and health reforms are implemented, the balance is chaging somewhat. It seems that more PhD's are looking for applied or clinically relevant diagnostic positions and clinical activities are more valued. One positive development to maximize the expertise of each group is evolving in the creation of multidisciplinary approaches in the genetic predisposition to inherited neoplasias. Geneticists, molecular diagnostic labs, medical oncologists, and surgeons are creating comprehensive care programs for patients with MEN, or inherited forms of breast and colon cancer. As the human genome project elucidates more gene-disease correlations the integration of genetics into many medical disciplines will become necessary. As professionals we have a tremendous responsibility of education of ourselves, colleagues, and the public. Thank you for reminding those of us in the US that we are still fortunate to be working in our system, imperfect as it is. Barb Zehnbauer, PhD FACMG Molecular Diagnostic Lab Washington University Medical School bzehnbau@imgate.wustl.edu ************************************************************** In response to your note on: WIDENING GAP BETWEEN "CLINICIANS" AND "SCIENTISTS" Your analysis of the problem in clinical research was intriguing. However there were a number of points that I found to be contradictory to my experiences working in biomedical research in Australia, the United States and Italy. In this field (perhaps not true for "clinical research" as such) the problem is relatively straight forward -- "Clinicians" trained for clinical work should not venture into an arena where they do not have the skills and training. The laboratory interests they have should be bridged by the appropriate means of communication; be it frequent meetings with the scientists or through appropriately trained "mediators" To follow the trend in Law over the past decade or more, specially trained lawyers have been required to bridge the gap between "scientific" data and jury comprehension during trial. Although most may consider that perhaps not such a large gap needs to be bridged in the "clinician" / "scientist" context, a similar opening for specialised "mediators" may be appearing. A scientist spends 7 to 10 years gaining the experience and qualifications to head a research project. These qualifications do not allow the "scientist" to do clinical rounds or clinical research just because he/she may have an interest in patients!!! Why then does the "clinician" (qualified only for the clinic and/or clincal research) feel suitably qualified to wander to the bench? Does clinical training also permit the "clinician" to work at any other "bench" say if he/she is interested in Law? Or, for those wishing a more pertinent example: why then is an experienced theatre nurse not permitted to operate on patients? -- the same reason... The knowledge is probably more than adequate but the "qualifications" and, importantly, the "details" are missing. I am not saying that "clinicians" are not capable of performing one or both tasks: in fact there are endless cases where this is more than exemplified. However, one must choose between "clinician" and "scientist" -- in the long run there is nothing worse for both professions (and separate professions they are), and "professionals", than to have a "clinician" having his/her time distracted from the tasks for which they are qualified and spent on things for which they may have only adequate knowledge -- TWO 50% EFFORTS IN DIFFERENT "PROFESSIONS" DOES NOT MAKE A PROFESSIONAL! There are ample opportunities (e.g. in the US - see below) for one to further their education to deal more appropriately with the more "specialised and focus demanding" requirements of their chosen profession. Certainly in Australia (which follows effectively the English style of Post-graduate programs), university qualified researchers (PhDs in particular) are the primary "directors" of research ("scientists") -- both biomedical and basic. In the areas of Medical Genetic Research these scientists are frequently found in the hospital-based environment or at least have a direct connection with relevant "clinicians". As a general rule (as emphasised above), no "clinician" is permitted to enter the biomedical research "domain" unless he/she returns to university to gain the appropriate theory and practical skills necessary. And, obviously, the converse holds true. In the States, although undeniably the best place for interactive, supportive biomedical research (and similarly could be said perhaps for other areas of research) the problem you describe is becoming apparent particularly in a number of the more notable medical colleges. Also, in accordance with your comments on the Italian system, this problem is most noticeable in this country - at least in the hospital based research settings on which I can only comment. Here, in many labs, the PhD (whether US, UK or Aust) appear to be the hands of the "clinicians", who frequently have given up their clinical duties (if ever initiated - and majority I have met fall into this category) to "devote themselves to scientific research". "Clinicians" surprisingly consider themselves the "thinkers" and are motivated by the "political appearance". The nearly non-existent funding for non-medical research, however, may be one cause of this "acceptable inter-profession migration". However, the beleaguered higher education system here must take the brunt of the blame for the appalling status,in recent years, (certainly not true a decade or more ago) of "scientists" from this country. An "internationally-recognised" equivalent of, for example, the UK / US / Aust PhD does not appear to exist these days in Italy. Any gap between existing "clinicians" and scientists surely then only highlights the shortfall of the higher education system in all the countries where a widening gap is appearing. The US seems to be (and have been doing so for some time) buffering themselves against such a occurrence by having in place specialised tertiary (and other postgraduate) courses such as in Clinical Genetics. This, I believe, is one of the major reasons behind the success and "dominance" of biomedical (and perhaps clinical) research in the US. When will other countries wake up? Timothy Cox, PhD Visiting Postdoctoral Fellow Tigem - Telethon Institute of Genetics and Medicine Via Olgettina 58 20132 Milan - Italy tel 39-2-21560221 fax 39-2-21560220 tcox@andromeda.hsr.it ************************************************************** Your analysis of clinical versus basic research trends was most intersting and certainly worthy of concern and discussion. As you must be aware, Dr. Varmus ordered a review of funding trends for clinical versus basic research grants at the behest of clinical scholars who felt that regular study sections (first level peer review in the NIH system) were not "fair" to clinical applications or at the very least, tended to fund less of them. This distinctive polarity tends to hit everyone eventually, and create several camps that tend not to have the same experiences in their professional lives and hence may have different expectations and prejudices. I am fearful that the distinguished crop of physician-scientists that spearheaded the NIH in the decades afters its formation are few and far between today. I do not think that special funding devices, such as the physician scientist awards from the NIH, that provide greater levels of financial support to professionally trained persons (e.g. MD, DDS, DVM, DO and etc) rather than "straight" PhDs, or the NIH's intramural supplemental stipends to professionally trained individuals or the disparate salary lines paid to professionally trained members of house staffs help reduce the polarity. It does create a conflict to pay a postdoctoral fellow more simply because they have the MD degree than a similarly qualified individual with a PhD, even when it is likely that the PhD fellow will at least initially be more productive in a "cross-over" training experience. These are rubs that create friction because they are obvious and not justified. As per the NIH funding of clinical grants, it is my perspective that clinical applications are very very hard to write and often fail in study section because the hypothesis, methods of data generation, data analysis, outcome predictions and hypothesis testing is not as rigorous as when a "bench" trained scientist writes an application. In fact, when clinical grants are well constructed and incorporate these points they do very well in study sections and this was borne out by an ad hoc group who examined this question for the division of research rants. Still, we can hardly expect to make progress in the field unless we work more closely with one another, bing mindfull of the differences among training experience between bench or bedside researchers. One is not better than the other, just different. In these times of diminished financial support for NIH sponsored research projects, it is important to present a unified front and to lobby American Congressman for more of all types of support for meritorious studies. I refer anyone interested in the marriage of basic and clinical research to the comments by Am. Soc Cell Biol public policy chair, Dr. Marc Kirscher who addressed these issues in a particularly stimulating statement, as did Dr. Phil Sharpe in testimony to Congress (both of these are available from the Am Soc Cell Biol by email at ASCBINFO@ASCB.FASEB.ORG It is important for all of us to make our wishes known to American Congress persons and to help diminish the growing gap between individuals with different raining but the underlying desire to explore the unknown and help those who are ill. From: Malcolm Snead <mlsnead@ZYGOTE.HSC.USC.EDU> ************************************************************** Dear Editor, I enjoyed your analysis. As a German working in the US, I whole-heartedly agree with the statement about the difference between Europe and US, and Germany being one of the most segregated societies in terms of research/clinic: My German friends ALWAYS have a good laugh when I, a Ph.D., state that my tenure track faculty position here in the US is in Psychiatry. That is inconceivable and incomprehensable in Germany! I do think that the trend in Europe is towards bettering the situation - the Max Delbrueck Center in Berlin specifically claims that that's what it wants to achieve, and has a clinic with beds connected to a basic research center, a rarity if not unique situation in Germany. It is too early to judge its success, but at least the need was seen and addressed. It is my impression that the trend in the US is indeed such that it is getting harder for M.D.'s and Ph.D.'s to get together. Due to tightening funding and job opportunities, there is more animosity between M.D.'s and Ph.D.'s - as there is a general trend of less cooperativity and more competition among scientists in general - unfortunately. Ph.D.'s realize that MD's usually have a better or far better salary, and often can fall back on a higher percent clinical work if they are not funded for a while. On the other hand, MD's feel that their time commitment for research is lower because of their clinical duties, yet they are judged for their research at the same level with Ph.D.'s when promotion and funding is concerned, and find it hard to compete with them. They also often have to fight for their protected research time - when an M.D. with a previous high clinical load gets an NIH K-award for 75% research effort, I have seen calculations assuming 70 hours/week for faculty, so 25% clinical=17.5 hours =1 day plus two half days which then get expanded due to "unexpected clinical load" from the morning into the afternoon, leaving de factor 2 protected days for research that equal 75% effort. There is one factor you didn't mention, and that is MSTP's or MD/Ph.D.'s. I have the impression that the best research at the border between basic and clinical is mostly carried out by MD/PhD's, and is harder and harder to get into by anyone else. I don't know the statistics but my impression is that the number of MD/PhD's has increased significantly over the last few years, and given that funding/jobs are tight, they are mostly the ones doing the research that you are talking about. This is also where Europe is lacking - M.D./Ph.D.'s are rare or non-existing there. Funding? I am amazed about your conclusion that basic/clinical research gets less well funded than basic even in the US - estonishing if correct. That deserves a better look, especially which way the trend goes. I would think that with NIH ear-marking more money for clinical (e.g. breast cancer/AIDS) research with a basically zero-growth budget, there is a higher fraction of money for clinical or clinically-oriented basic research. I fear that if the impression from politicians agrees with your analysis, that there isn't enough money in the more clinically oriented research arena that even more money as already is taken away from basic research - we have to be careful in promoting a shift without being sure that that is justified. Margit Burmeister, University of Michigan (margit@umich.edu) ************************************************************** Certainly the pressures of trends in American medicine bode ill for the clinician/scientist. While previously, inpatient medicine was the modal one for academics, it is becoming more and more necessarily to treat patients out of the hospital, and thus clinical income is mainly earned in the OP clinic. You can't very well have "rotations" in the OPD like you do on the floors. Research grants become harder to get and margins of teaching hospitals are slimmer and slimmer, forcing physicians to earn more of their income from seeing patients. ------------------------------------------------------------------------------ Gordon Banks N3JXP |"There is nothing so terrible as ignorance in action." geb@cadre.dsl.pitt.edu | --Goethe ----------------------------------------------------------------------------- ************************************************************** Thanks for sharing your thoughts with us. I largely agree with what you said, especially with the first part of your text, about the two separate paradigms. I wish to add some information about what is going on in France. I am the director of an INSERM unit (id supported by public funds), which is totally dedicated to clinical research in genetics. Its name is "Gene mapping and clinical research". We are not suppose to do the research ourselves , but develop and distribute tools to facilitate the collaboration between biologists and clinicians. We have created a database, called GENINFO (http://www.infobiogen.fr) which contains all the research projects, both biological and clinical, going on in France, to stimulate the collaborations. We also advertize them by mailing to all relevant clinicians in France. INSERM has also created several other units called "centers for clinical research" which are co-supported by the hospitals where they are located. They are open to any project which requires a technical medical support. The patients can stay for the day and have all the necessary exams, performed by nurses and technicians in clinical research who are trained to complete detailed questionnaires. The Ministry of Research distributes also some funds specifically for clinical research, but you are right to say that this type of research is not supported enough. Segolene Ayme, MD ayme@LOVELACE.INFOBIOGEN.FR ************************************************************** ************************************************************** Editor's reply. I thanks the many people that sent replies and comments on this important and delicate issue. Here you have just seen some of these replies; I ask pardon to all of those who did not find their message posted. As you can see, most replies shared the opinions expressed in the editorial. I want to stress that my analysis was restricted to the very limited field of translational research (phase I-II studies), and is not pertinent to basic research or routine clinical care. Interestingly the two replies most critical with the present situation of translational research came from two persons (Cox and Burmeister) with research experience in Italy and Germany. Burmeister cites the Max Delbrueck Center in Berlin as possible catalyzer for changing the german situation. I hope so, although my (limited) knowledge of this center points more toward a physical proximity than to a cultural one. Many centers in Germany (and Italy as well) have clinical wards physically close to research labs, but completely separated in terms of personnel, organization and priorities. Tay and Ayme report their experience in countries as different as Singapore and France. Momtahan cites a personal experience stressing the importance of combined clinical/lab experience and globalization of information (one of the aims of HMG) in the management of rare diseases, while Huggings look at the problem from the perspective of a genetic counsellor. Hong asks whether clinician/scientists are in a better position to lead teams composed by scientists and clinicians; my answer is yes, stated that such teams do exist in the local situation. The need and importance for the development of multidisciplinary, disease-oriented teams is highlighted by Zehnbauer and Snead (both working in the US). Cox is instead highly critical of inexperienced MD who enter the lab environment without proper training; there is no doubt that sufficient training is needed for working in a lab (as in any other profession, however). This is a real problem in countries (like Italy) where MD do not get any serious exposure to research during their training; this type of conflict, however reflects also the lack of communication/collaboration depicted in my analysis. Some people was surprised by my conclusion that basic research gets more support than clinical research, even in the US. That was based on publication analysis of just three months of MedLine; therefore it has to be judged for what it is, a small and preliminary analysis. Banks and Burmeister, finally, cite practical examples about difficulties in integrating clinical and lab activity even in the US. Certainly rotations in outpatient clinics are not possible, but one weekly clinic is quite compatible with a research activity (if they do not become 2-3-4/week). To assume a typical working week of 70 hours in order to justify a "75% research efforts" coupled with 2-3 days/week of clinical activity, reflects in my opinion the consequence of the present situation where people are asked to do 2 jobs instead of one. Instead, the role for "physician/scientists" is in my opinion critical for the successful exploitation of basic molecular information. A critical factor resides in the availability of new treatments to be tested; the investigation of purely diagnostic assays in fact does not require a so close clinical/laboratory integration, and can be performed by more separate teams. Carlo Gambacorti MD ************************************************************** ************************************************************** A note from the DIAGnostics/Clinical Research Editor ************************************************************** WIDENING GAP BETWEEN "CLINICIANS" AND "SCIENTISTS" ************************************************************** This note is intended to stimulate debate and discussion on a topic that I consider very important for most HUM-MOLGEN subscribers. Rapid and efficient translation of preclinical data into early clinical studies represents a critical problem in biomedical research. Modern science is becoming more and more specialized and focus demanding. In addition, clinical and lab activity follow quite different and often contradictory rules. Thus, it could seem natural that different individuals will deal with preclinical (the "scientist") and with clinical (the "clinician") research. Such an organization can work for basic research and for advanced clinical studies (phase III-IV). In the delicate field of "translational research" (pilot, phase I-II studies), this separation of duties carries with it a significant risk: to create two almost independent and mutually impermeable systems. The field of molecular genetics is quite exposed to this problem, since more and more techniques (usually developed by people with little or no clinical experience) are entering the clinical arena (where few people have consistent lab background). In the extreme of this context (let's call it the "schizophrenic theater") the two players have different goals: molecular modeling (independently from its clinical relevance), papers and grants on one side, tailoring of existing treatments (independently from their often marginal value), patients and money on the other. Paradoxically, the development of new treatment modalities is not a first priority for anybody. The two participants in this surrealistic game do not know each other situation sufficiently well to perceive and understand the other side problems and perspectives. Reciprocal misunderstandings and distrust can develop. This results in an inefficient translational research. I can supply interested readers more than one such example. Having worked both in Europe and in the US I think the situation is different in the two continents, although a similar trend is emerging. In Europe this represents an endemic problem. The organization of work tends to ask a 100% clinical commitment to people in clinical departments (the concept of rotation is mostly unknown) and to put non clinicians in separate departments with their own structures, hierarchies and directors. It is usual that clinical studies list the involved personnel in two separate columns, one for the clinicians and one for the non-clinically involved staff. While these divergent goals can (perhaps) be more easily reconciled inside the management of a private company, this is more difficult to be accomplished in entities like research institutions and universities characterized by a high degree of complexity and independence of different departments. There is no defined granting agency or program, specifically designed to fund clinical research or the clinical component of a research project, whose cost usually rests over the respective national health system, with all its pros and cons. Some past attempts at creating clinical research centers, on the example of american GCRC, have been found to be incompatible with the existing structures or were mainly "political" attempts (Nature, 369,92, 1994, Nature 361, Jan.21, classified #2 and #5, 1993). The problem is more evident in some countries (Italy and Germany are to my knowledge the worst examples) where a more pyramidal organization is present inside hospitals and universities, and perhaps less in the UK. In the US many of the above mentioned problems do not exist, even if the situation for clinical research is far from optimal there too (Nature, 371, 468, 1994). Rotations are usual in clinical departments, thereby freeing research-protected time. Clinical training usually include at least some research-oriented time (in hematology and medical oncology for example). Programs like the NIH-funded General Clinical Research Center (GCRC) do exist and assure financial support and extra-mural peer review for clinical protocols. Recently, however, a trend toward a more demarcated separation between lab and clinical activity is emerging. Most people working as "clinician-scientists", with whom I recently spoke, find more and more difficult to remain in this position, without losing competitiveness. There is a diffuse feeling of inadequacy to compete for grants with PhDs, who do not have any clinical burden and are often technologically more experienced, on one side, and to compare with people on clinical tracks, who have far higher clinical volumes and therefore carry more clinical revenues to the institution. This editor does not mean that everybody inside an university hospital should become a physician-scientists, but that a critical number of such professional figures should be allowed to successfully work in an institution encompassing both clinical and lab activity, to avoid or limit the above mentioned difficulties. Some publication data can be illuminating: I looked at the first 3 months of MedLine 1995, and searched for all publications with CLINICAL/RESEARCH (mostly pilot, phase I-II studies) among keywords. Among the 208 papers, 2/3 come from North America (42% of them acknowledging public support), 1/3 from the rest of the world (31% with public funding). Data concerning publications from more basic fields (like for example HLA/PEPTIDE), show publication from North America (US + Canada) accounting for only 42% of total (68% of them with some public funding), the rest of the world getting the remaining 58% (with 80% acknowledging public funding). What these data do tell us ? In my opinion four things: 1. original clinical research is best played in america (little doubt about it), where, 2., it also gets a level of public financial support higher than in the rest of the world (42% vs. 31%); 3. clinical research, however, is in general less likely to get public funding than basic research, and this, 4. is particularly evident for non american countries (31% vs. 80%). Although there is wide acknowledgment on this issue (J. Clin. Oncol., 11, 1639-51, 1993, Nature, 371, 468, 1994, American Association for Cancer Research, Association News, March 29, 1994, pages 1-2, Nature Medicine, 1, 281, 1995), little (Nature, 376, 547, 1995) is being actually done. I hope this short piece can result in an healthy debate. Questions that interested readers could try to answer are: 1. do you agree in general with this analysis ? 2. do you think this trend represents an inevitable development ? 3. do you have comments, ideas or proposals ? Carlo Gambacorti MD, Editor, Human Molecular Genetics network Diagnostics/Clinical Research Section HUM-MOLGEN@NIC.SURFNET.NL