INTRODUCTION

The development of new pharmaceutical products is important to advance ophthalmology as a medical specialty and to reduce the suffering and blindness of patients.Blindness and visual impairment affect an estimated 300-400 million people globally and around 80% of people living with blindness are aged 50 and above[1-2]. Considering ageing populations an investment in an ophthalmic startup may be attractive because of the potential for financial payback, perhaps as much as seven to tenfold[3-5]. However,investing in ophthalmic start-up companies also carries risks as the overall success rate is low[6-8].

The ophthalmic community is benefited by at least 190 companies investigating more than 436 new medications in a wide variety of therapeutic areas[9]. As encouraging as is the number of new medications being developed, many are focused on a limited number of therapeutic areas including:wet or dry age-related macular degeneration, glaucoma or dry eye[10-11]. Considering the extensive regulatory time and money required to develop a new medication as well as the current competitive environment having so many companies focused on so few areas, raises questions about the ef fi ciency of resource utilization within the ophthalmic community[10-13].

The purpose of this survey was to inquire of ophthalmologists,who have participated as investigators, and ophthalmic pharmaceutical professionals, involved in ocular research and development, their perceived needs of new medications in various ophthalmic subspecialties. We desire to assist those considering establishing new start-up companies or development plans by providing information helpful for choosing an appropriate treatment indication.

SUBJECTS AND METHODS

Two contact lists were compiled: a list of ophthalmic industry professionals who have been involved in ocular research and development; and a list of ophthalmologists who have actively participated in clinical research. The survey was developed on Survey Monkey (www.surveymonkey.com) and the link to the survey was sent via email. The link was sent two additional times following the initial distribution.

10月24日，在海洋钻井公司举办的“企业开放日”活动中，新胜利五号钻井平台副经理袭润祥指着平台设备间里的一个大家伙告诉前来参观的记者说：“这是我们投入100多万元购置的一体化污水处理设备。平台上产生的污水通过不同的管道收集起来，经过处理达到国家排放标准后排海。连落在平台上的雨水我们也有专门的回收系统，不仅避免了雨水将平台上的污染物带进大海，也实现了雨水的循环利用。”至今，海洋钻井公司已累计投资千万元对所有钻井平台实施了“零排放”改造，效果显著。

The survey was developed by several of the authors. Questions were based on issues derived from personal discussions with ophthalmic colleagues and based on treatments described in the medical literature. The survey questions are shown in the Figure 1.

When the expression of commitment for physicians was compared to pharma professionals, generally physicians statistical indicated more potential commitment to a new needed product. The reason for this finding is unclear.Physicians would have the advantage of perceiving needs from a patient based level which may heighten commitment. In contrast, a pharma professional might be in a lesser position to express sometimes of commitment to a new medicine such as lecturing.

The survey link was distributed to 559 ophthalmic pharma professionals and ophthalmologists. We received 82 (15%)responses of which 21 (26%) were pharma professionals and 61 (74%) were physicians (Table 1).

Figure 1 Survey questions.

Statistical Analysis All statistical tests were non-paired, twosided and used a P-value of 0.05. The sample population was not powered statistically since the study’s intent generally was a descriptive, non-comparative survey. A one-way ANOVA test was used to evaluate each comparison on this study[14].

RESULTS

This study adheres to the guidelines of the Declaration of Helsinki. Due to the survey design of this research project Institutional Review Board/Ethics Committee approval and clinical trial registration was not required.

The survey showed that the most commonly perceived needs(on a ranked scale of 0 to 5) were dry age-related macular degeneration with an average score of 4.5, wet age-related macular degeneration 4.0, glaucoma 3.8, diabetic macular edema 3.8 and dry eye 3.5. There was a statistical difference found between all selections (P＜0.0001).

Although there are limited studies similar study to ours regarding perceived therapeutic needs in ophthalmology[8,11].We found several online surveys sponsored by ophthalmic societies that included devices as well. The Fight for SightSurvey of health professionals and patients also indicated age-related macular degeneration and glaucoma, but added cataract, corneal diseases and childhood disorders[18]. The National Eye Institute Panel of ophthalmic experts also noted a similar top fi ve list as the Fight for Sight Survey[19]. And there have been reports discussing the need for new retinal disease and dry eye treatments[20-21]. Our survey differed in that our therapies were limited to: practitioner and pharma professional respondents. Device and pediatric treatments were not offered as a choice in our survey.

DISCUSSION

This survey of ophthalmic pharma professionals andophthalmologists showed the highest perceived needs for new ophthalmic medications were for dry and wet age-related macular degeneration, glaucoma, diabetic macular edema and dry eye. The indication of dry and wet age-related macular degeneration is not surprising because these common diseases have very few treatments to help suffering patients[15]. In addition, diabetic macular edema and glaucoma are potentially visually disabling diseases and their treatments, while effective,are not curative and not generally sight restorative[16-17]. Dry eye is a chronic cause of discomfort, disrupted vision and reduced quality of life in a high percentage of the population. Common treatments are palliative and can reverse the condition only to a limited extent.

Table 1 Survey respondent demographics n=82; n (%)

Gender M 66 (80)F 16 (20)Age (y)31-40 5 (6)41-50 17 (21)51-60 36 (44)＞60 24 (29)Geographical region Northeast 11 (13)Southeast 22 (27)Midwest 11 (13)Southwest 6 (7)West 17 (21)Europe 10 (12)Other 5 (6)Type of practice General ophthalmology 11 (13)Mixed general ophthalmology and subspecialty 15 (18)Subspecialty (see below) 33 (40)Pharmaceutical professional 21 (26)Retired doctor 2 (2)Subspecialty area (more than one answer allowed)Cornea and external disease 8 (10)Cataract and refractive surgery 15 (18)Glaucoma 31 (38)Uveitis and ocular immunology 1 (1)Vitreoretinal diseases 5 (6)Ophthalmic plastic surgery 1 (1)Pediatric ophthalmology 1 (1)Neuro-ophthalmology 0 (0)Ophthalmic pathology 1 (1)

Respondents indicated they would express their commitment to a new product they perceived as needed by recommending to colleagues (63%), prescribing (60%), participating as principle investigator in a related clinical trial (52%), advising the company (52%), lecturing on behalf of the product (43%),investing in the product (38%), taking no action (7%) or obtain a position in the company (1%). When the results from physicians were compared to pharma professionals there was a statistical difference across all answers (P=0.0006; Table 2).Generally physicians perceived more clinical needs than did pharma professionals, especially in glaucoma, age-related macular degeneration, and for anti-infectives.

Table 2 Comparisons between physician and pharma professional responses for area of perceived need and how they would express their commitment to chosen need n (%)

aThese choices were excluded from the analysis since it applied only to practicing physicians.

43 (70) N/A Advise the sponsoring company 34 (56) 10 (48)Lecture on behalf of the product 33 (54) 2 (10)Invest in the product startup 22 (36) 9 (43)Take no action 1 (2) 5 (24)Obtain a position in the company 0 (0) 1 (5)Pharma professionals(n=21)Indication of perceived need Glaucoma 28 (46) 1 (5)Wet age-related macular degeneration 28 (46) 5 (24)Dry age-related macular degeneration 40 (66) 10 (48)Dry eye 13 (21) 4 (19)Diabetic macular edema 16 (26) 7 (33)Postop. anti-in fl ammatory 0 (0) 0 (0)Anti-infective 10 (16) 1 (5)Presbyopia 14 (23) 3 (14)Uveitis 7 (11) 3 (14)Allergy 2 (3) 1 (5)Cataract 9 (15) 3 (14)How would you express your commitment to the product?Recommend the product to colleagues 47 (77) 5 (24)Prescribe the producta 49 (80) N/A Become a principle investigator in a clinical triala Parameters Physicians(n=61)

However, the results of this survey for less needy areas, compared to the number of pharmaceutical companies developing medicines under each therapeutic area by our internal data, appeared to diverge. Respondents indicated that even therapeutic areas perceived as requiring less assistance still had a reasonably high needs level (2.2-3.2 for cataract, uveitis,presbyopia, anti-infective and post-operative inflammatory conditions, on a ranked scale of 0 to 5). However, the associated decrease in the number of companies making new products in the perceived less needy areas is much greater[9].The reasons for this disparity are not known. However, selecting the indication best suited to a medicine under development is a complicated process which includes assessing not only physicians’ patients’ perceived needs, but the required regulatory pathway, route of delivery, total costs and time involved, potential treatment population and market penetration of this patient group and associated reimbursement[6].Consequently, the disparity in the number of medicines being developed between the areas of the greater to lesser perceived needs could be due to the other development factors mentioned above and may be deserving of future research.

Nonetheless, this disparity between perceived need and the number of products currently being developed could point to the utility of new companies to examine, early in the development process, at least the perceived needs of physicians and the competitive environment to better help guide the therapeutic indication choice.

Interestingly, the therapeutic areas indicated by survey respondents as having the greatest therapeutic need generally match the areas where the pharmaceutical companies are developing new treatments. In a recent study it was found that approximately 59% (257/436) of the new medicines being developed were in age-related macular degeneration (both types), glaucoma, dry eye and diabetic macular edema[9]. In addition, the internal development goals of a number of large pharma companies also follow in these areas (William Stewart,personal communication, PRN, USA).

赵燕梅和伙伴们，从严把车辆进站入手，对所有进站车辆的车容车貌、装卸油口、电子封签、油品专用标识，以及灭火器、接地线等安全防护点，进行严格细致的检查，绝不放过一个隐患，打造了“青年文明号”品牌。

其次，研究通信网络的另一种有效工具就是仿真分析法。由于通信网络中固有的随机性和离散性，纯粹用数学方法已很难解决问题，所以仿真分析法就成为分析通信网络性能的有效方法，其中具有代表性的就是摄动分析法（Perturbation Analysis，PA）[5]。它既有理论计算，又有仿真试验，吸取了两者的优点，很容易对DEDS的统计性能进行优化分析。所以，PA方法是排队网理论和计算机仿真分析的创造性结合。

我国水资源总量为28 412亿m3，居世界第六位，人均水资源量约2 100 m3，为世界平均值的28%。人多水少、水资源时空分布不均是我国的基本国情和水情。水资源的有效开发利用有力地支撑了经济社会的快速发展，但总量不足和水质恶化导致的水资源短缺也成为制约我国经济社会发展一大“瓶颈”。

This survey showed that ophthalmic pharma professionals and ophthalmologists perceive the greatest need for new medicines in ophthalmology to be in dry as well as wet age-related macular degeneration, glaucoma, diabetic macular edema and dry eye. More research is needed generally regarding the best way to utilize start-up funds and personnel talent to most efficiently and profitably develop new medications for ophthalmic patients.

ACKNOWLEDGEMENTS

Authors’ contributions: Stewart WC, concept and development,editing; Stewart JA, concept and development, editing; Nelson LA, data collection/analysis, references.

式中α和β均为任意复数，表示两种状态的概率幅度，满足正交性，|α|2和|β|2分别表示两种状态的概率。与经典比特不同，量子位不仅可以处于0态或1态，还可以处于两个基本状态的线性叠加。在计算过程中，每个不同量子的概率幅会互相干涉，并且可以进行量子并行计算。完成编码后，初始化种群P(t):

Conflicts of Interest: Stewart WC, None; Stewart JA, None;Nelson LA, None.

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