Conflicts arise at many steps and levels of functioning, and they are related to the expectations, competing interests, and conflicting priorities of the different entities involved, whether they are the academic medical centers, the funding agencies, the patients and their families, or the investors and venture capitalists. Let us take up some of them here.
1. The Public
The public expects access to new treatments. Its appetite for innovation has been bolstered by the constant attention given by the press to new treatments and by the implicit promise from researchers of continuing advances. Direct-to-consumer advertising of drugs has increased the public's awareness of new developments in medicine, especially with respect to the treatment of common conditions, with the secondary effect of raising expectations (and health care spending) still further (Moses, Braunwald, Martin and Their, 2002).
New treatments being continuously discussed in the media adds to the appetite, and expectations, of a novelty hungry public. And a whole mass of lips macking industry and opportunistic academia may latch on to this want with glee. How best to articulate genuine aspirations and eschew ulterior motives is the prime intellectual task of concerned academia as much as of serious pharmaceutical players. For, even the latter, if they have to remain long term in the field, will have to lay down certain ethical parameters that sustain their growth without hampering patient welfare. If they do otherwise, they may survive for a while, but will continuously be the target of justified malpractice suits and negative publicity, along with greater checks and balances being put in by governmental authorities and demanded by patient rights advocates, and a consumer-welfare aware, if sensation seeking, media.
Hardly a situation that fuels growth.
2. The Patients
Patients demand privacy and control over information about themselves. Information about genetic predisposition is especially troublesome to patient groups and privacy advocates, not only because of the unknown implications for patients and their families, but also because of the fear that once the information proves to be commercially valuable, it will become more difficult to control. These issues led in part to the passage of such legislation as the Health Information Portability and Accountability Act of 1995 and weighed heavily as the act was subsequently modified (Kulynych and Korn, 2002) (Moses, Braunwald, Martin and Their, 2002).
Genetic predisposition information as collected in research protocols is a real dilemma. Whilst knowing it is essential to enhance patients’ interest, the advocacy groups nurse an apprehension not knowing how the information maybe utilized. How much of it will be considered and how much suppressed, especially when a commercially viable drug is at hand which can dramatically alter company balance sheets? Legislation is a necessary but often poor remedy. A clear protocol to reveal details of whether genetic predisposition impacts a certain drug is essential as a declaration in all drug research publications, just as conflict of interest at present is.
Related also is the integration of roles that a researcher must carry out to minimize potential conflict between competing loyalties that may hamper optimal care of patients volunteering for research. The roles of clinician and scientist must be integrated to manage conscientiously the ethical complexity, ambiguity, and tensions between the potentially competing loyalties of science and care of volunteer patients (Miller, Rosenstein and DeRenzo, 1998).
A healthy skepticism of the scientists’ findings by the clinician, and a healthy respect for the needs of the practicing physician in the scientist may go a long way to bridge the gap, and increase connectedness all around.
3. Companies, large and small
A thought provoking insight into the way the size of a company affects its objectives in relation to academia is offered here:
The objectives of companies in their relationships to academia often vary according to the size of the company. Large pharmaceutical companies see great value in access to academic talent, ideas, and research tools and de-emphasize the importance of discrete inventions and patentable discoveries. In contrast, smaller companies, especially those that develop devices and diagnostic techniques, see greater value in obtaining late-stage technology (i.e., products that are near clinical trial) that are closer to market. These companies derive considerable value from their association with reputable institutions and investigators, which validates their efforts to raise venture capital and the potential value of the company and its product (Moses, Braunwald, Martin and Their, 2002).
This is an interesting observation about the differences in ways of functioning of large and small pharmaceutical companies. That the larger ones give greater value to continued access to academic talent, ideas, and research tools means they believe in long- term associations that sustain (probably ethically) over a longer period of time. That they de-emphasize the importance of discrete inventions and patentable discoveries means they may seek but are not obsessed with short term gains, which is but appropriate for long term players if they wish to sustain themselves over time. However, the smaller companies seek late-stage technology, and with ample justification. They are small players with limited capital, but an obsession to grow big and fast. That is possible only by palpable profits pouring in quickly, which late-stage technology provides very well indeed. Such companies woo venture capital armed with this technology, and understandably so. That they also woo researchers who have made a name for themselves to be part of their set-up in advisory/consultative capacity is equally understandable, for they have to continuously prove their credentials to others, as much as to themselves.
In this process, the Davids may make a killing at the expense of Goliaths of the pharmaceutical industry. It makes greater sense, therefore, for genuine researchers to associate with large long-term players who have a track record of genuine hardcore discoveries, even if the process is slow (maybe), and the funding less (may not be). Of course, if the researcher wants to grow fast, as much in wealth as in reach, he should know whom to approach, though be ready to be manipulated by market forces and shady operators in such companies who will maximize profits by side tracking him when it suits them, no explanations given. This is of course no guarantee that the large operators would not do likewise, but the risk is lesser, as is the frequency of such happenings. For they are used to a certain approach, and have a certain strong credibility to protect, and are hardly likely to indulge in petty deeds as a norm unless someone treads too sharply on their toes. The smaller ones would have no qualms of taking such action. This, of course, does not mean exceptions do not exist in both categories.
4. Venture capital
The venture capitalists, especially in smaller companies, are the people who are in it mainly for profits. The pharmaceutical company, howsoever small, can be expected to have some qualms. Since they have to continuously interact with the medical profession, practicing doctors researchers or academia, they have to maintain at least a semblance of accountability to patient welfare. The venture capitalists, on the other hand, need have no such qualms at all. They can lay down their terms and conditions, and enforce them pretty ruthlessly. Their greater presence in industry is a new challenge to academia, to which an appropriate response is needed:
Venture investors in these entities reinforce the importance of establishing the investigators’ full commitment and making it public and visible (Moses, Braunwald, Martin and Their, 2002).
Indeed, for any nexus between investigators and investors should be exposed, and any blurring of boundaries firmly resisted. But the presence of venture capital can become a good ploy to increase profitability for the pharmaceutical companies that depend on them, citing the former's pressures to suit their own profit motives too. In this whole game, if patient welfare can be served, great. If not, well, sorry, but that's the name of the game. Such games playing can also occur, which researchers and academia need to be aware of.
The element of control venture capitalists exert over the pharmaceutical industry is an under researched area for obvious reasons. But it needs further probing, for that will lay bare the pulls and pressures under which industry works. If there used to be a ‘investor's lobby’ in real estate which controlled the builders and the market rates, there seems to be a parallel phenomena in pharmaceuticals which controls the manufacturers and the areas of research too. Some more probing in this area would make many skeletons tumble out of industry cupboards.
That venture capitalists should insist on researchers making financial stakes in their funded concerns is but plausible, for that ensures for them the researchers’ total commitment to maximizing profit, even at the cost of ethical or patient considerations if need be. Hence, the insistence that researchers declare their financial stakes in companies whose products they research, as they do other data to declare conflict of interest, is an eminently worthy idea to implement.
5. Stocks and Equity
Let us also look at the other manner commitment to profits is ensured by industry:
The most common vehicle used to assure such commitment is equity or stock options assigned to the investigator and, with increasing frequency, to the institution where the work is performed (Moses, Braunwald, Martin and Their, 2002).
That investigators and even institutions should consider equity/stock options an attractive investment, especially as they have what could be considered ‘insider-information’, and maybe offered such options free or at substantially discounted rates, makes for potentially dangerous portents. While all may be fine if the products are really worthy, the problem comes if they bomb, or are found to have serious side-effects, or involve multiple legal cases or public interest litigations (PILs). In which case the company bottom-lines can go hopelessly in the red, especially if they are small companies mainly dependent on venture capitalists. Here researchers may be forced to toe the PRO line of the company involved.
In other words, it makes sense for ethically minded researchers and institutions not to fall in the trap of such investments, howsoever attractive they appear, and get rid of such stocks as soon as possible if they have them. If at all they want, it makes more sense to own stocks of larger well established concerns, for the stock upheavals being less, the pressure of the market-place, and of venture sharks, is likely to be lower too. They may also seriously consider whether owning stocks as a part of, or consequent to, research funding should be forsaken for long-term peace of mind. In any case, there is no social benefit attached to researchers owning stocks:
But it is highly doubtful whether many of the other financial arrangements facilitate technology transfer or confer any other social benefit. For example, there is no conceivable social benefit in researchers’ having equity interest in companies whose products they are studying (Angell, 2000).
As far as stocks of young companies go:
Stock or options in young companies are relatively affordable, since they become valuable only if the company and product become successful. Active participation by the investigator in the commercialization process is viewed as essential in creating value. This engenders a powerful but controversial incentive for the investigator and has proved to be one of the most difficult issues for academic centers to manage (Moses, Braunwald, Martin and Their, 2002).
While active participation by the researcher in the commercialization process may be greatly desired by industry, ostensibly in the name of creating value, academia must realize it is a bait it might find hard to swallow in the long run. It makes more sense for the researcher and institution to forego such temptations and/or walk out of such investments as soon as possible:
Institutions and institutional decision makers should fully disclose industry related financial interests and relationships. Without legitimate justification for such interests, individuals should divest themselves from these interests (Johns, Barnes and Florencio, 2003).
However, considering the realities of the market place this may be easier said than done, especially for those investigators who depend on small/ medium enterprises which themselves depend on venture capitalists, or heavily borrowed capital.
The intricacies of how economics plays a strong role in the whole process of research investigation is highly complex, and need detailed study on their own. Although one often feels one is better off being blissfully unaware of its intricacies. Which is probably the reason it is under probed, and may so remain. Both manifestations of our denial, which may prove costly in the long run.
A survey of the scenario yields certain mixed portents. While mainstream medicine and research are booming, as is connected industry, concerns about professional commitment to patient welfare are growing too. Increasing corporate influence is challenging certain long held and fundamental values of patient care, which will have far reaching implications for biomedical care and the future progress of mainstream medicine. Events in the next two-three decades will decide the fate of modern medicine and connected industry.
The tug of war between commercial interests and ethical concerns promises to be a roller coaster one. Hold on to your seats, gentlemen.*