Hemostasis Current Treatment Practices XX Country Country Report Qualitative Market Research

Transcription

1 HealthQ International HemoStatis Current Treatment Practices Hemostasis Current Treatment Practices XX Country Country Report Qualitative Market Research Prepared for: Prepared by: HealthQ International

2 HealthQ International HemoStatis Current Treatment Practices 2 Methodology and Sample

3 HealthQ International HemoStatis Current Treatment Practices 3 Methodology and Screening Criteria Sixteen respondents were interviewed in XX Country using the in-person individual-depth interview (IDI) methodology. On average, each interview took 45 minutes to complete. 16 Neuro Surgeons Average 4 years in practice All perform surgeries at teaching hospitals Range of 5 to 50 surgeons on staff at hospitals Many also have private practices 16 General Surgeons Average 8.5 years in practice 5 performing surgeries at teaching hospitals 1 from Major Academic Center Range of 5 to 50 surgeons on staff at hospitals Many also have private practices 14 Pharmacy Directors Average 9 years in position All from teaching hospitals Range of 15 to 50 pharmacists on staff All serve on procurement committees and all have responsibility in new products evaluation and selection All respondents were recruited from research vendor databases, and all met the following screening criteria: More than 40 beds in hospital; >50% of time devoted to see patients; At least 25 procedures (physicians) required the use of a topical hemostatic agent, specifically thrombin (with or without a sponge or other mechanical); Use of thrombin in at least 5 procedures per month; 35% of their patients had private insurance or paid out of pocket.

4 HealthQ International HemoStatis Current Treatment Practices 4 Sample Description 16 Neuro Surgeons Hospitals bed size: Average: 153 beds Range: beds Number of surgical procedures requiring topical hemostats (per month): Average: 39 Range: Number of surgical procedures requiring thrombin* products (per month): Average: 11 Range: General Surgeons Hospitals bed size: Average: 175 beds Range: beds Number of surgical procedures requiring topical hemostats (per month): Average: 31 Range: Number of surgical procedures requiring thrombin* products (per month): Average: 8 Range: Pharmacy Directors Hospitals bed size: Average: 119 beds Range: beds All respondents hospitals stock thrombin* products Thrombin-JMI is not stocked in hospitals * In XX Country, this sample of respondents (MDs and Pharm Directors) do not distinguish between active thrombin or pure thrombin, e.g., Thrombin-JMI and thrombin-containing products, e.g., Xseal, Tisseel.

5 HealthQ International HemoStatis Current Treatment Practices 5 Current Perceptions and Practices

6 HealthQ International HemoStatis Current Treatment Practices 6 Surgeries performed depend on surgeons specialties Surgeons mention the following as most common surgeries performed: Most Common Neurosurgeries Craniotomy due to aneurism and tumor removal/resection, Laminectomy fusion, Discectomy, Microdiscectomy, Meningiomas and Hypophysis/pituitary gland tumors Most Common General Surgeries Abdominal and colorectal surgery, Arteriovenous graft, Cholecystectomy (Gall bladder) and Appendix Many of the most common surgeries mentioned above were associated to bleeding, additional examples include: Cerebral vascular disease, spleen laceration, malformations of the spine, lumbar and cervical spine, open heart surgeries, partial kidney tumor resections, radical prostatectomy, and prosthesis replacement. Pharmacy Directors mentioned that all types of surgeries are performed in their hospitals.

7 HealthQ International HemoStatis Current Treatment Practices 7 Hemostatic agents are often used only after all other means of hemostasis have been tried 1) Surgeons first try to avoid excessive bleeding 2) If bleeding continues, other ways to stop the bleeding are tried 3) Topical Hemostatic agents are used as a last resort In most cases, surgeons feel they use surgical techniques to manage bleeding during the surgical procedure. Means to avoid bleeding include: Performing less invasive surgeries to limit the damage. Using specific techniques to limit contact with the surrounding structure. Using strong sutures to close the incision. Using bipolar/monopolar radio frequency and ultrasound knives. When hemostasis is required, compression, gauze and cauterization tend to be options prior to topical hemostatics. Few mentioned that in liver surgeries A good normal hemostasia and cauterization is not used because precise it can closing cause is more my best damage. ally to have a successful surgery and recovery. Some exceptions seem to exist for the Neurosurgeons, who use topical hemostatics before - Neurosurgeon, the other specialties XX since the tissue involved in their procedures Country calls for greater caution in the use of cautery.

8 HealthQ International HemoStatis Current Treatment Practices 8 Surgeons manage bleeding in surgical procedures with various topical Hemostasis products Most common spontaneously mentioned hemostatic products are: SurgX (Fibrillar /nuknit) xfoam Tisxl xflow xseal xplast In this sample, just one or two respondents in XX Country mention: XXX Xcel xclot I can manage bleeding with all of the good products there are on the market, from XXfoam to XXgicel and reach up to XXX or XXXX. - General Surgeon, XX Country When prompted about ZZZZ none of the surgeons in this sample knew or had used the product. One respondent mentioned that in XX Country that ZZZZZ is no longer available; thrombin is currently used in combination products only.

9 HealthQ International HemoStatis Current Treatment Practices 9 Perceived advantages and disadvantages of Hemostasis Products Non-Thrombin-containing Hemostasis Products Product Advantages Disadvantages Xoam XXgicel Cheaper Easy to use/ preserve Most hospitals have it available No need to prepare Easier to apply than foam Covers more bleeding area For more regular areas Not seen in the CT scan It can be left inside the patients- does not produce mass effects Available and easy to manipulate Different presentations Needs a lot to cover bleeding Has less hemostasia It is seen in the CT scan and confuses surgeons Does not stick very well The material density is uncomfortable for delicate areas It becomes loose and it needs to be discarded and reapplied Not as potent as products with thrombin Can not be applied in irregular surfaces Need to apply pressure to gain hemostasia Not great for artery bleeding (XXX) (XX) Improved hemostasia Can be easily separated into pieces Can be applied as cotton Used for important vascular bleeding Can be rolled and molded Easy to apply in difficult to reach areas Easy to manipulate Dense knit material, more dense than SurgX and faster Its good as a suture It tears apart very easily It is often wasted Not good for artery bleeding Can only be used for defined sections

10 HealthQ International HemoStatis Current Treatment Practices 10 Nearly all XX Country surgeons have experience with thrombin-containing products It is important to note that in this sample, XX Country surgeons do not distinguish between active/pure thrombin versus thrombin-containing topical hemostats. All surgeons in this sample describe the preparation methods correctly for each of the three thrombin products (when compared to available on-line information), thus indicating that they are speaking about the proper product(s). XX Country-specific summary of pros and cons are as follows: Product Advantages Disadvantages TissX Xseal Xplast Faster and greater hemostasia (than non-thrombin containing products) Seals fistulae better Administration is convenient Useful for difficult areas to reach Used in brain; Often used as a sealant in dura mater More specifically for vascular hemorrhage, specifically blood vessel and artery bleeding and vascular anastomosis More adherence property than Tissucol Coagulated slower in the syringe (more time to use) Has adapters for laparoscopy Used for pediatric surgeries due to smaller presentation Similar to Tissucol Good hemostasia and sealant action More liquid than the other Xseal or Tissucol Most representative support/presence Less expensive than the other thrombin-containing products More expensive Cannot easily manipulate tissue after application; may require re-application thus leading to waste and increased cost Needs 20 minutes to be prepared Needs to be prepared Its needs to be in the freezer The syringe can be tampered The most expensive in the market None mentioned The Xplast drops are very convenient as they can be used in small quantities. - Neurosurgeon, XX Country I use Xseal for venous bleeding when I do not know were its coming from as it stops hemorrhage rapidly. - General Surgeon, XX Country

11 HealthQ International HemoStatis Current Treatment Practices 11 Thrombin-containing agents have specific advantages over non-thrombin containing hemostatic agents Advantages of Thrombins* Disadvantages of Thrombins + Faster time to achieve hemostasia as fast as 5 minutes. + Less quantity needed to achieve hemostasia and surgeons use what they need without leaving solid waste. + Mode of application allows it to be introduced in small and difficult to reach places. + Absorbs adequately so it can be left inside the body tissues without the worry of generating adverse events. - Cost is the primary complaint associated with thrombins. - While some respondents say that thrombins are easy to apply, others claimed that they are more difficult to prepare. - The pressure leaks in the syringe so the product is activated and coagulates inside the syringe, thus sealing the conduit. - Some mentioned that the products containing fibrins coagulate faster and thus wastes more product. What I really like about thrombins is that its application allows it to enter into the smallest places where we need hemostasia. - Neurosurgeon, XX Country *According to this sample of respondents, pure thrombin, i.e., Thrombin-JMI is not longer available in XX Country.

12 HealthQ International HemoStatis Current Treatment Practices 12 Product Selection and Availability

13 HealthQ International HemoStatis Current Treatment Practices 13 Surgeons select hemostatic products based on a variety of factors Overall, selection of hemostatic product selection is based on the following, in order of importance: Availability in the hospital Surgeon s experience with product, ease of use, & colleague endorsement Type of surgery amount of bleeding expected or seen* Patient-specific factors, e.g., age and comorbidities (rare mention) Cost (Primary concern for Pharmacy Directors) Surgeons report hemostatic products they require are generally available at their hospitals. Some respondents mention manufacturer supply issues has caused temporary switches. In public hospitals, it is more common that the desired product is not available, but there are adequate substitutes. In general all respondents agreed that their colleagues at the hospital share the same general approach to technique/product selection. I have found myself asking for SurgX and they would only have foam, or ask for SurgX Fibrillar and they would only have SurgX. -General Surgeon, XX Country *See discussion on p10. I really use what is available at the hospital, the chief of nurses and the chief of surgery are the ones that may know better the options as they are the ones that know which products are used the most. - General Surgeon, XX Country All respondents state vehemently that the nurses only participate in preparing the product and never in making a product selection. XX Country General Surgeons in this sample, indicate that if Xseal was too expensive to the patient or to the hospital, they are happy to use SurgX or foam.

14 HealthQ International HemoStatis Current Treatment Practices 14 Cost and manufacturer availability are main guidelines for hemostatic product use Both surgeons and pharmacy directors report that, overall, no formal guidelines exist for the selection of hemostatic products for surgical use. Pharmacy directors give the following, additional reasons for product availability and selection within their hospitals: US FDA, COFEPRIS Cost Hemostat Selection Surgeon preference Our hospital does not have specific guidelines, the main guideline is efficacy and cost. - Pharmacy Director, XX Country Hospital committee consensus Manufacturers product availability Relation-ships and contracting with suppliers

15 HealthQ International HemoStatis Current Treatment Practices 15 Physicians select hemostatic products mostly during surgery; exceptions are for cash-paying patients Most respondents interviewed from XX Country report that they decide on the specific hemostatic product at the time of surgery, based on the general criteria discussed previously. Surgeons in XX Country s public hospitals many times are able to suggest a better product for a patient, and thus they need to plan in advance so patients can buy it before the surgery. Respondents from XX Country stated that their timing for asking for a product could range from 24 to 48 hours in advance, but most of them did not worry as their hospitals could provide additional product in few minutes. The chief of department or the chief of nurses in conjunction with the PD (administrative department) are the ones that make the request of the hemostatic products. If I have a craniotomy where I know I might need additional hemostasia, I can call the administrative department 24 in advance to let them know the products I will be using - Neurosurgeon, XX Country We make the request of the hemostatic products and either the Pharma Company or the distributor will provide them to our hospital so that we have always on stock - Pharmacy Director, XX Country Few mentioned that in emergency surgeries such as trauma accidents, they may not have enough product in the operation room - but they would have it as soon as the general pharmacy would provide it from their stock. Similarly, pharmacy directors state that they always try to have an advanced stock of the products that surgeons will need for their surgeries. They mentioned that they had the smaller pharmacy and the bigger warehouse pharmacy were they can ask for more product if needed. This is my work, I need to provide what the surgeon will use, and that is why we are continuously revising our stocks and the surgeons needs - Pharmacy Director, XX Country

16 HealthQ International HemoStatis Current Treatment Practices 16 Respondents report a relatively standardized process for adopting new products (see appendix for details) Option 1 Origination Surgeon Evaluation Form or Letter Admin. Committee Medical Committee Nurses Committee Identification Pharmacy Director Chief of Surgery Chief of Operation Rooms Surgeon s Product Presentation Option 1 Decision Committee s VOTE Cost-Benefit Analysis Contact Pharma Company Acceptance Buy and Stock Origination Option 2 Identification Decision Option 2 Surgeon Evaluation Form or Letter Pharmacy Director Contacts Pharma Company to have samples and presentation Cost-benefit analysis Buy and Stock

17 HealthQ International HemoStatis Current Treatment Practices 17 Current Unmet Needs

18 HealthQ International HemoStatis Current Treatment Practices 18 Surgeons and pharmacy directors express a concise list of current hemostatic unmet needs Current Unmet Needs (In order of priority) Faster and more efficiently in diminishing bleeding Product cost More emphasis by Pharmacy Directors Multiple application methods Easier preparation and storage No need to freeze/defrost Longer expiration date Training by manufacturers Reasons Promote better surgical outcomes and faster patient recovery Reduce surgical time Reduce hospital cost Avoiding blood loss and transfusions While hemostat products may play a small role in most surgeries, they can be very costly Would like to save patients money Reduce hospital cost Need ability to be adapted for laparoscopy surgeries Less product waste Less nursing time and training Less product waste Faster usability Would be a distinguishing feature for manufacturer Save physicians time in training nursing staff If a new and better product is on the market and its also cheaper I would push myself to stock it!! That is for sure. - Pharmacy Director, XX Country I really would need a product for my brain surgeries that could be liquid because it can seal faster and that it can cover the layer bleeding at 100%. - Neurosurgeon, XX Country My main unmet need is that SurgX and foam is not enough to stop the bleeding in some surgeries, so I need to use much product, therefore I would be more than willing to use a product with greater hemostasia. - General Surgeon, XX Country

19 HealthQ International HemoStatis Current Treatment Practices 19 Potential adoption of new hemostatic agents driven by satisfying unmet needs & current guiding principles Nearly all surgeons interviewed are not aware of any new hemostatic products on the horizon. A few mention that they never actively research the area of hemostats. Two XX Country surgeons have had heard of Xseal but have not used it. One XX Country surgeon mentioned he had heard about growth factors being used in hemostasia. For adoption of a new hemostat product, respondents cite the following factors: Faster onset of action Greater efficacy in stemming bleeds Low side effects No risk of infections (human products) US FDA, COFEPRIS & Secretaria de Salud approved Equivalent or superior pricing to current products New biotechnology Pharmaceutical company presence/ presentation KOL endorsement, Dr. Guindo, Societies I can change the products I use if the new one is really faster to achieve hemostasia and does not cause adverse events. -General Surgeon, XX Country The Pharmaceutical Company is key in presenting to us a new product in this area. - General Surgeon, XX Country I think that Dr. Evandro de Oliveira and Dr. Ali Krisht are the top Neurosurgeons that can make a good recommendation about a new product. - Neurosurgeon, XX Country

20 HealthQ International HemoStatis Current Treatment Practices 20 Reactions to Product X Profile

21 HealthQ International HemoStatis Current Treatment Practices 21 Product Profile Hypothetical Product Indication Characteristics Product X Thrombin, topical (Recombinant) is indicated as an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques is ineffective or impractical. May be used in conjunction with an absorbable gelatin sponge, USP. Product X Thrombin, topical (Recombinant), is human thrombin produced via recombinant DNA technology from a genetically modified Chinese hamster ovary (CHO) cell line, a commonly used expression system for producing recombinant proteins. Product X is identical in amino acid sequence to naturally occurring human thrombin In a randomized, double-blind phase 3 clinical trial, 401 patients at 34 study sites undergoing spinal, vascular, or liver surgery received either Product X (1000 IU/mL) or bovine thrombin (1000 IU/mL, Thrombin-JMI). Product X promotes rapid, reliable hemostasis: Efficacy Dosing and Administration Side Effect Profile Product X is supplied as a white lyophilized powder in 5,000-unit and 20,000-unit vials and can be stored at room temperature for up to 24 months. Lyophilized Product X is reconstituted with normal saline using a needle-less transfer device (diluent in a pre-filled syringe provided in the kit) Product X may be topically applied directly to a bleeding site or in conjunction with an absorbable gelatin sponge, USP. Multiple application methods via: Absorbable gelatin sponge, Absorbable gelatin powder, absorbable gelatin matrix, Pump and Syringe spray devices. The safety and immunogenicity observations from 8 completed Product X clinical trials (n=583) were pooled for analysis. The most commonly reported adverse event were incision site pain (51%), procedural pain (30%), and nausea (28%), which are consistent with those commonly observed in surgical patients Product X has a favorable immunogenicity profile <1% (n=5/552) of all patients developed antibodies to Product X. Rates of antibody formation to Product X across these clinical trials ranged from 0 to 1.6% at day 29. None of the antibodies neutralized to native human thrombin

22 HealthQ International HemoStatis Current Treatment Practices 22 Respondents point to a number of benefits: onset of action & novel recombinant technology as greatest attributes Current Unmet Needs (In order of priority) Benefits of Product X (in order of importance) Faster and more efficiently in diminishing bleeding [Product Safety was not a stated unmet need, but is the 2 nd most important benefit of Product X] Many respondents are impressed by the percentage of patients who achieve hemostasis at three minutes. However, many do not feel that the time to hemostasis is strongly different from currently available products. Can be combined with other hemostatic products and thus have even greater efficacy. The fact that it is obtained from a recombinant DNA technology which in turn generates less immunogenicity and other adverse events is seen as a definite advantage. However, some questioned the side effects listed in the product profile, noting that they do not have similar concerns with other agents. Product cost More emphasis by Pharmacy Directors Not immediately seen as a strength of Product X: Respondents assume that a new product would be more expensive. I am really impressed on how this thrombin was produced- its identical to human thrombin but its recombinant. - Neurosurgeon, XX Country

23 HealthQ International HemoStatis Current Treatment Practices 23 Overall, Product X immediately satisfies 3 out of 5 top unmet needs Current Unmet Needs (In order of priority) Multiple application methods Easier preparation and storage No need to freeze/defrost Longer expiration date Benefits of Product X (in order of importance) Several application advantages are noted: The different application methods offer flexibility in use with different types of surgeries/surgeons. The ability to be applied directly to the bleeding site. Other products need to have dry tissue to be applied. When prompted about the application method most surgeons mentioned they would prefer the pump and syringe spray devices followed by the absorbable gelatin sponge. They thought that the spray presentation helps to reach larger areas with smaller amounts of product. The no refrigeration requirements and up to 24 months storage are likewise viewed positively. Training by manufacturers Not immediately seen as a strength of Product X Having all of this application forms makes me think of Product X as four different products for many surgeries. - General Surgeon, XX Country What I really like most is that it activates when it contacts the bleeding site - and not before, and that leads me to think that it does not adhere to the tissue and works perfectly for Hemostasia. - General Surgeon, XX Country I can save a lot of money for my hospital if the product that I am buying can be stored up to 24 months at a room temperature. - Pharmacy Director, XX Country

24 HealthQ International HemoStatis Current Treatment Practices 24 Surgeons envision a number of different applications for Product X Surgeons foresee the most value for surgeries with excessive bleeding. They feel they can control minor bleeds themselves. Examples of surgeries mentioned (partial list) Tumors, meningiomas Open heart surgeries; bypass, valve replacement Aneurysms Vascular malformations/surgeries Brain tissue Some pediatric procedures Malformations of the spine Transsphenoidal surgeries (hypofisis) I would use it in craniotomy as it could be used in advance to prevent bleeding- as we do it with Tissucol. - Neurosurgeon, XX Country A number of surgeons also mentioned laparoscopic surgeries. Given the formulation, they believe the application is well suited for these procedures. A few patient driven factors were identified: Age was not as important in considering the use of Product X but some surgeons were more worried about co-morbidities such as heart and blood conditions. Patients who use antiplatelet products (aspirin) would not be suitable candidates. It is easy to prepare and has that many methods, then it would be ideal in laparoscopic surgeries - General Surgeon, XX Country

25 HealthQ International HemoStatis Current Treatment Practices 25 Cost is perceived to be the primary potential drawback of the product; and availability is a potential concern Surgeons and Pharmacy Directors point to cost as the main barrier for product acceptance, particularly in public hospitals in XX Country. However, a number of Pharmacy Directors in XX Country indicated that the cost of $810 pesos for a 5ml vial is a reasonable price for a thrombin product. Just one Pharmacy Director from a lower income hospital considered it somewhat more expensive than what they had, as they got special stock prices for certain contracts with Pharmaceutical Companies. There were some questions and concerns surrounding product availability. Some surgeons questioned the availability of the product, especially those in XX Country who mentioned that some hemostatic products have been not available for certain periods of time. Other concerns were the possibility to find it in every pharmacy or that most distributors would have them for delivery to all hospitals. I believe $810 pesos is much lower than what we pay for Xseal- this is a great option if its going to cost this. - Pharmacy Director, XX Country I need to know that I will have access to the product and that my hospital will always have it when I decide to use it- if it is not like that, I will continue to use the products I trust. -Neurosurgeon, XX Country I hope that the product is not very expensive, that way it can be stocked faster in my hospital once we have analyze its benefits. - Pharmacy Director, XX Country

26 HealthQ International HemoStatis Current Treatment Practices 26 Experience, education, and exposure are critical to product acceptance. Manufacturer training ad support Manufacturer training for the surgeons and nurses was voiced by many of the respondents in order to gain exposure to the product. Some suggested a workshop organized by the Pharmaceutical Company specially dedicated to the preparation and administration methods- as well as the devices needed. Many respondents mentioned that they would like to see the sales reps visit them and leave them samples. Expert endorsement would raise awareness Various respondents, mainly from XX Country, envisioned themselves as the ones introducing Product X to their hospital. Several suggested increasing awareness by finding a professor who defends the adoption of the new product to increase the impact on the decision of standardizing a new material. Presence at meetings and lectures is important to create familiarity with the product. The best way that I will find out that the product exists is from a sales rep who will show it to me. General Surgeon, XX Country Experience is important A number of surgeons would want to evaluate the product for themselves prior to fully adopting it. Some respondents said that at the beginning they would use it in surgeries that have low risk of heavy bleeding. From there, they would evaluate use in riskier surgeries with greater risk of heavy bleeding.

27 HealthQ International HemoStatis Current Treatment Practices 27 Additionally samples and scientific literature would kickstart adoption Availability of Samples Many respondents ask for free samples out-right, such that they can gain personal and first-hand experience of Product X As well, personal experience will also translate into personal endorsement of Product X, thus feeding into expert endorsement and overall awareness in hospitals. Engaging senior surgeons, department heads, and professors with samples would be worthwhile. Try it and see it for myself that is the best recommendation I can have! Neurosurgeon, XX Country Availability of Research Information/ Monographs Several physicians also request scientific information from manufacturers, in addition to sale rep presentations. Important sources of reliable information mentioned include: Neurosurgery Society Neurosurgery (journal) Academy of Surgery In order to use a new product, I would need to see medical publications from an international, independent researcher. Neurosurgeon, XX Country

28 HealthQ International HemoStatis Current Treatment Practices 28 Conclusions & Recommendations

29 HealthQ International HemoStatis Current Treatment Practices 29 Surgeons immediately saw uses for Product X for specific types of surgeries Product X Perceptions Product X is viewed positively in XX Country The primary points of interest appear to be the novel recombinant DNA technology and the multiple application methods. These attributes are perceived as having definite advantages over current products. Other benefits include: - Fast onset of action: comparisons should be made to the hemostatics currently used in the country rather than other thrombins. - Easy to stock: This point is especially important to the Pharmacists Items for Consideration Strongly communicate the primary benefits and reasons to use Product X in order to motivate use over current modalties. Product X Use Physicians point out that this agent would be most useful in surgeries where heavier bleeding is anticipated. At present, many do not use topical hemostatics for minor surgeries or bleeding unless the bleeding cannot be stopped. As such, this product is preceived as intended for serious and extreme cases, not for routine surgeries. Surgeons tend not to give much forethought to the hemostatic product used and will make decisions based on what is currently available to them in the operating room. The perception that minor bleeding does not require the use of topical hemostatics should be corrected by calling attention to the possibility of even more effective results than are currently being achieved. Invest in educating surgeons on the differeces between hemostatic agents and utility of Product X over current modalities.

30 HealthQ International HemoStatis Current Treatment Practices 30 Perceived cost and product awareness are the two potentially greatest obstacles Product X will face Cost Barrier Perceive cost is a primary driver of adoption of new hemostatic agents and may present a barrier to the uptake of Product X initially. However, specifically in XX Country, respondents (MDs and pharmacy directors) agree that Xseal is extremely expensive, and any product that provides greater safety, efficacy, and convenience at a parity or lower price, would be a winner Items for Consideration Develop a strong materials showing mainly the possible cost and time gained with the adoption of the new hemostatic. Product X Use and Perceptions Generating a level of comfort and familiarity will be essential. Surgeons and pharmacy directors perceived that a good presence/training from sales reps and distributors/ pharmaceutical companies would driver a higher likelihood of selection of the product. Key Opinion Leaders have a great importance in the adoption on new materials. Approval from US FDA as well as local XX Country authorities is essential in considering a new product in the XX Country Actively approach hospitals to provide in-service training to raise awareness and level of comfort about the product. Associate at least one renowned surgeon (or team) with the product to boost its credibility and awareness.

31 HealthQ International HemoStatis Current Treatment Practices 31 Appendix: Additional Details

32 HealthQ International HemoStatis Current Treatment Practices 32 Stocking Decision Tree Details The first requirement to obtain a product is that it has to be previously authorized by the FDA and have proven experience. Surgeons mentioned that in order to obtain a product that is not stocked in their hospital they need to write a proposal mentioning the benefits of the product and why they want it. Some may even need to present the results from a Study or Protocol. Others need to make a presentation themselves to convince the different committees. Few mentioned that there was a formal format to ask for new products. These are product evaluation sheets that have different parts were the benefits are mentioned and then the product is compared to the ones already stocked. The administrative department makes the decision to substitute another product or add to the stock. Other respondents from XX Country mentioned that they would need to pose the requirement to their chief of surgery/department so that together they can write to the administrative department. Few respondents mentioned that the first one in charge of submitting the letters was the chief of nurses or the person in charge of all the operation rooms. Then these would need to be presented to the different committees (Administrative, Medical and Nurses) so they can evaluate the product, vote, and make the authorization. If I know there exists a new product I just need to write a letter stating the benefits and why I want it, then present it to the Pharmacy Director or Administrative Department and they start the process to stock the product. - General Surgeon, XX Country

33 HealthQ International HemoStatis Current Treatment Practices 33 Stocking Decision Tree Details Pharmacy Directors mentioned that they are constantly evaluating new products and their analysis is based mainly in a cost-benefit approach. Generally, they belong to an administrative committee that meets periodically (every 1~3 months) to review new products, make procurement decisions, as well as to discuss other issues pertaining to products kept at their pharmacy. The administrative department together with the chiefs of surgery/nurses or medical department evaluate the product and then an outcome is given to buy or not the specific product. Some surgeons and Pharmacy Directors from both countries mentioned that certain Pharmaceutical Companies were close to them and that they gave them samples and presentations so they were more keen in getting their attention and require their product. They also mentioned these same companies trained them and their nurses in order to be more knowledgeable of their product and thus that would make them chose it more frequently. Respondents from XX Country and PR stated that their private hospitals could take 5 to 10 days to authorize a new product and as long as 1 to 3 months. For the public sector in XX Country it could range from 1 month to 6 months. Few surgeons from XX Country mentioned that as their hospital was private, the responsibility was theirs so they just needed to ask for it and they would have the supply. I am open to any suggestion a surgeon would have to stock a new product, but their presentation has to be convincing and at the end we would stock the product if the cost is worth the benefits. - Pharmacy Director, XX Country I am the only responsible of prescribing or using a certain product, so my hospital would stock what I ask for as long as it is approved by the FDA. - Neurosurgeon, XX Country

34 HealthQ International HemoStatis Current Treatment Practices 34 Perceived advantages and disadvantages of Hemostasis Products Thrombin-containing Hemostasis Products Product Advantages Disadvantages Surgiflo Tissucol Xseal Xplast Perclot Has good hemostasia Can be used as a spray Can be used easily for the hepatic area/gall bladder Faster and greater hemostasia Seals fistulae better Administration is convenient Useful for difficult areas to reach Used in brain Used to isolate bleeding areas Its is absorbed in the tissue Often used as a sealant in dura mater For blood vessel bleeding Great for artery bleeding Coagulates less faster in syringe Effective Has adapters for laparoscopy Good for open heart surgeries Effective in brain surgeries Similar to Tissucol Good hemostasia and sealant action More liquid than the other Xseal or Tissucol Useful in brain (craniotomy) surgeries Its a powder and its very manageable Good for difficult to access areas Good for hypophysis It adheres good to the gall bladder walls Not mentioned Coagulates so fast that product is wasted, it gets stuck in the syringe and not useful after a while More expensive As it is liquid it can flow to unintended areas Its wasted because they do not have the equipment on hand to apply it Needs to be prepared Needs to be prepared Its needs to be in the freezer The syringe can be tampered The most expensive in the market Less expensive than the other thrombin-containing products Expensive Not always available